HIV clinical trials and vaccine starting in the 80's


RE© I am the original source for researching and explaining the HIV biological and vaccine information on my blog page. This information was transferred from my original sources of e-mails, facebook postings, files and other sources I've detailed and collected since 2009.

E-mail I sent to a researcher on: On Apr 17, 2017, at 8:51 AM

Did I send you all those recent papers on the super recomibinations of HIV. I think I may have for Cuba, Russia the Phillipines and China? If you want to see them, I can resend.

Response e-mail:

From: xxxxx

Sent: Monday, April 17, 2017 8:57 AM

If you could resend all of the papers that would be great!
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Original E-mail I sent: 

Sat 12/31/2016 10:14 AM

To: xxxxx

This is the stuff they were doing in China in 2011. This is at the Chinese CDC and that Shao YM was has been working on vaccine development for awhile. This is the CRF07_BC strain. Also in this paper it claims they did not even have adequate equipment to be working with these retroviruses:

Up to date, no published genomic sequences from virion RNA are available for Chinese prevalent HIV-1 strains due to the absence of specialized protocol and appropriate lab equipments. In this study we developed a straightforward approach for amplifying and sequencing HIV virion RNA from plasma by modifying published protocols and further confirmed it is suitable to process Chinese samples. https://www.ncbi.nlm.nih.gov/pubmed/21362385

Chin Med J (Engl). 2009 Dec 5;122(23):2874-9. https://www.ncbi.nlm.nih.gov/pubmed/20092794

Construction and characterization of a new simian/human ...

www.ncbi.nlm.nih.gov

1. Chin Med J (Engl). 2009 Dec 5;122(23):2874-9. Construction and characterization of a new simian/human immunodeficiency viruses clone carrying an env gene derived ...

Construction and characterization of a new simian/human immunodeficiency viruses clone carrying an env gene derived from a CRF07_BC strain.

Li Y1, Yang GB, Chen QM, Liu Q, Meng ZF, Geng YQ, Qiao WT, Shao YM.

Author information

Abstract

BACKGROUND:

The CRF07_BC recombinant strain has been one of the most predominantly circulated HIV-1 strains in China, it is therefore necessary and urgent to develop a relevant animal model to evaluate candidate vaccines targeting HIV-1 CRF07_BC. A highly replication-competent simian/human immunodeficiency viruses (SHIV) construct containing the Chinese CRF07_BC HIV-1 env gene with the ability to infect Chinese rhesus monkeys would serve as an important tool in the development of HIV vaccines. The aim of this study was to examine whether SHIV XJDC6431 with the env fragment from a Chinese HIV-1 isolate virus could infect the human and monkey peripheral blood mononuclear cell (PBMC), establish infection in Chinese rhesus macaque.

METHODS:

A SHIV strain was constructed by replacing the rev/env genes of SHIV KB9 with the corresponding fragment derived from the HIV-1 CRF07_BC strain. The infectious activity of the SHIV clones was determined in vitro in PBMCs from both non-human primate animals and humans. Finally, one Chinese rhesus macaques (Macaca mulatta) was infected with one SHIV via intravenous infusion.

RESULTS:

One SHIV clone designated as SHIV XJDC6431, was generated that could infect macaque and human PBMC. The virus produced from this clone also efficiently infected the CCR5-expressing GHOST cell lines, indicating that it uses CCR5 as its coreceptor. Finally, the virus was intravenously inoculated into one Chinese rhesus macaque. Eventually, the animal became infected as shown by the occurrence of viremia within 3 of infection. The viral load reached 105 copies of viral RNA per ml of plasma during the acute phase of infection and lasted for 10 weeks post infection.

CONCLUSIONS:

We conclude that SHIV XJDC6431 is an R5-tropic chimeric virus, which can establish infection not only in vitro but also in vivo in the Chinese rhesus macaque. Although the animal inoculated with SHIV XJDC6431 became infected without developing a pathologic phenotype, the virus efficiently replicated with a persistent level of viral load in the plasma. This suggested that the SHIV could be used as a tool to test candidate AIDS vaccines targeting the Chinese HIV-1 CRF_07BC recombinant strain.
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This is an e-mail I sent to others explaining what I found while researching HIV vaccine trials:

Sent On Apr 17, 2017, at 8:02 AM

Just look what's happening in Asia, Cuba and Russia with the multiple recombinations. They've created a super Hiv that progresses to AIDS within 3 months.

http://www.thebodypro.com/content/79434/hiv-vaccine-plus-latency-reactivator-induces-susta.html?ic=ms
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Original E-mail I sent: 

Sent: Tuesday, March 21, 2017 6:13 PM

Recommended HIV/AIDS Strategies for Hong Kong 2007-2011

Final draft

Hong Kong Advisory Council on AIDS

http://www.info.gov.hk/archive/consult/2007/aids_e.pdf
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Original E-mail I sent: 

Fri 1/6/2017 11:24 PM

To: xxxxx

From the article: "However, it is important to note that approximately one-quarter to one-third of HIV-2-infected patients without ART will have HIV-2 RNA levels below the limits of detection; some of these patients will have clinical progression and CD4 cell count decline. No validated HIV-2 genotypic or phenotypic antiretroviral (ARV) resistance assays are available for clinical use."

Clinical Course of HIV-2 Infection

Compared to HIV-1 infection, the clinical course of HIV-2 infection is generally characterized by a longer asymptomatic stage, lower plasma HIV-2 viral loads, and lower mortality rate.1,2 However, HIV-2 infection can also progress to AIDS over time. Concomitant HIV-1 and HIV-2 infection may occur and should be considered in patients from areas with a high prevalence of HIV-2.

Diagnosis of HIV-2 Infection

In the appropriate epidemiologic setting, HIV-2 infection should be suspected in patients with clinical conditions suggestive of HIV infection but with atypical serologic results (e.g., a positive screening assay with an indeterminate HIV-1 Western blot.3 The possibility of HIV-2 infection should also be considered in the appropriate epidemiologic setting in patients with serologically confirmed HIV infection but low or undetectable HIV-1 RNA levels or in those with declining CD4 T lymphocyte (CD4) cell counts despite apparent virologic suppression on antiretroviral therapy (ART).

The 2014 Centers for Disease Control and Prevention guidelines for HIV diagnostic testing4 recommend initial HIV testing using an HIV-1/HIV-2 antigen/antibody combination immunoassay and subsequent testing using an HIV-1/HIV-2 antibody differentiation immunoassay. The Multispot HIV-1/HIV-2 Rapid Test (Bio-Rad Laboratories) is Food and Drug Administration approved for differentiating HIV-1 from HIV-2 infection. Commercially available HIV-1 viral load assays do not reliably detect or quantify HIV-2.5,6Quantitative HIV-2 plasma RNA viral load testing has recently become available for clinical care at the University of Washington (http://depts.washington.edu/labweb/AboutLM/Contact.htm)7 and the New York State Department of Health (http://www.wadsworth.org/programs/id/bloodborne-viruses/clinical-testing/hiv-2-nucleic-acid).8 However, it is important to note that approximately one-quarter to one-third of HIV-2-infected patients without ART will have HIV-2 RNA levels below the limits of detection; some of these patients will have clinical progression and CD4 cell count decline. No validated HIV-2 genotypic or phenotypic antiretroviral (ARV) resistance assays are available for clinical use.

Treatment of HIV-2 Infection

To date, no randomized trials addressing the question of when to start ART or the choice of initial or second-line therapy for HIV-2 infection have been completed;9 thus, the optimal treatment strategy has not been defined. Three clinical trials to assess first-line ART for HIV-2 infection are currently underway; 2 are enrolling patients with CD4 counts <500 cells/mm3 (NCT016058090 and NCT02180438) and 1 is enrolling patients with CD4 count >200 and ≤600 cells/mm3 (NCT02150993). Although the optimal CD4 cell count threshold for initiating ART in HIV-2 infection is unknown, therapy should be started before there is clinical progression.

HIV-2 is intrinsically resistant to non-nucleoside reverse transcriptase inhibitors (NNRTI)10 and to enfuvirtide (T20).11 Data from in vitro studies suggest that HIV-2 is sensitive to the currently available nucleoside reverse transcriptase inhibitors (NRTIs), although with a lower barrier to resistance than HIV-1.12,13Darunavir (DRV), lopinavir (LPV), and saquinavir (SQV) are more active against HIV-2 than other approved protease inhibitors (PIs);14-17 one of these boosted PIs should be used if a PI-based regimen is used. Other PIs should be avoided because of their lack of ARV activity and high failure rates. The integrase strand transfer inhibitors (INSTIs) raltegravir (RAL), elvitegravir (EVG), and dolutegravir (DTG) have potent activity against HIV-2.18-21 The CCR5 antagonist maraviroc (MVC) appears active against some HIV-2 isolates;22 however, no approved assays to determine HIV-2 co-receptor tropism exist and HIV-2 is known to use many other minor co-receptors in addition to CCR5 and CXCR4.23

Several small studies suggest poor responses in HIV-2 infected individuals treated with some ARV regimens including dual-NRTI regimens; regimens containing NNRTI plus 2 NRTIs; and some unboosted PI-based regimens including nelfinavir (NFV) or indinavir (IDV) plus zidovudine (ZDV) and lamivudine (3TC); and atazanavir (ATV)-based regimens.9,24-27 Clinical data on the effectiveness of triple-NRTI regimens are conflicting.28,29 In general, HIV-2 active, boosted PI-containing regimens have resulted in more favorable virologic and immunologic responses than 2 or 3-NRTI-based regimens.29-31 However, CD4 cell recovery on therapy is generally poorer than that observed for HIV-1.31-33 INSTI-based regimens may also have favorable treatment responses.34,35 A recent large systematic review of ART for HIV-2-infected patients (n = 17 studies, 976 HIV-2 infected patients) was unable to conclude which specific regimens are preferred.36

Resistance-associated viral mutations to NRTIs, PIs and/or INSTIs commonly develop in HIV-2 infected patients while on therapy.24,29,37-41 Currently, HIV-2 transmitted drug resistance appears rare.42 In one small study, DTG was found to have activity as a second-line INSTI in some HIV-2 patients with extensive ARV experience and RAL resistance.43 Genotypic algorithms used to predict drug resistance in HIV-1 may not be applicable to HIV-2, because pathways and mutational patterns leading to resistance may differ between the HIV types.13,29,44

Some groups have recommended specific preferred and alternative regimens for initial therapy of HIV-2 infection;45-48however, currently, there are no controlled trial data to support the effectiveness of the recommended regimens. Pending more definitive data on outcomes in an ART-naive patient who has HIV-2 mono-infection or HIV-1/HIV-2 dual infection and requires treatment, a regimen containing two NRTIs plus an HIV-2 active boosted PI or INSTI should be initiated in HIV-2 infected individuals.

https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescent-arv-guidelines/24/hiv-2-infection
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Sat 1/7/2017 12:01 AM

http://www.avert.org/professionals/hiv-science/types-strains
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Sat 1/7/2017 12:07 AM

Yunnan battles new strain of HIV[2]- China Daily Asia
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E-mail sent to another on:

Sent: Sat 1/7/2017 12:13 AM

Diverse forms of HIV-1 among Burmese long-distance truck drivers imply their contribution to HIV-1 cross-border transmission. - PubMed - NCBI

Zhou YH, et al. BMC Infect Dis. 2014.
Show full citation

Abstract

BACKGROUND: The China-Myanmar border is a particularly interesting region that has very high prevalence of and considerable diversity of HIV-1 recombinants. Due to the transient nature of their work, long-distance truck drivers (LDTDs) have a comparatively high potential to become infected with HIV-1 and further spread virus to other individuals in the area they travel within. In this study, we hypothesized that Burmese LDTDs crossing the China-Myanmar border frequently may potentially be involved in the cross-border transmission of HIV, and contribute to the extremely high prevalence of HIV-1 inter-subtype recombinants in this border region.

METHODS: A molecular epidemiology study was conducted among 105 Burmese LDTDs between 2008 and 2010. HIV-1 genetic fragments including p17, pol, vif-vpr, vpr-env, and C2V3 were amplified and sequenced. The subtype characterization and HIV-1 transmission were determined by both phylogenetic and phylogeographic analyses.

RESULTS: Diverse forms of HIV-1, including subtypes CRF01_AE (41.9%), C (8.6%), B (4.8%), CRF02_AG (1.0%), and inter-subtype recombinants (33.3%), as well as dual infection (10.5%), were detected among the tested LDTDs. Phylogeographic analyses based on pure subtype revealed that 77.8% Burmese LDTDs acquired HIV-1 infection in Yunnan, and the others in Myanmar. Both the C-related and CRF01_AE-related recombinants from these LDTDs appeared to have close genetic relationship with those from IDUs in Myanmar and Dehong.

CONCLUSIONS: Burmese LDTDs may contribute to HIV-1 transmission along the China-Myanmar border. The results may provide some new perspective for understanding the on-going generation and prevalence of HIV-1 recombinants in the border region.

https://www.ncbi.nlm.nih.gov/m/pubmed/25158600/
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Original E-mail I sent: 

Sat 1/7/2017 12:30 AM

To: xxxxx

Could this be as a result of a Fauci's hiv vaccine trials over there!

Feb 29, 2008, a convoy of long-distance trucks crossed into China from Myanmar. The drivers lined up at the customs house in Jiegao, a border town in southwestern Yunnan province, for a regular HIV/AIDS test, and each was asked to provide 2 to 3 milliliters of blood.

One sample, provided by a 40-year-old driver from Myanmar, was found to be positive for antibodies of HIV - human immunodeficiency virus - but they were unlike any seen before, leading researchers to suspect that it was a previously unknown strain of the virus.

Their suspicions proved correct. "The strain has genetic segments from three subtypes, rather like the combined strands of DNA seen in people of mixed race," said Zheng Yongtang, from the Kunming Institute of Zoology at the Chinese Academy of Sciences, whose team conducted the research.

"Currently, we have no idea how dangerous the new strain is, because the research was based on analysis of ribonucleic acid in the blood, but the strain itself has not been extracted because of the small amount of blood provided for the test," he said.

In 2011, Zheng's team carried out genetic studies on 105 blood samples collected by the Yunnan International Travel Healthcare Center between 2008 and 2010. All the samples belonged to long-distance truck drivers from outside China, mainly from Myanmar.

Sample No 11 was the only one that carried the new strain, which was described as "one of the most complicated strains of HIV-1 ever detected in Myanmar - a recombinant (mix) of three different HIV subtypes", in a recent article in the journal AIDS Research and Human Retroviruses.d hiv getting mixed with mlvs and African green monkeys maybe!

On Feb 29, 2008, a convoy of long-distance trucks crossed into China from Myanmar. The drivers lined up at the customs house in Jiegao, a border town in southwestern Yunnan province, for a regular HIV/AIDS test, and each was asked to provide 2 to 3 milliliters of blood.

One sample, provided by a 40-year-old driver from Myanmar, was found to be positive for antibodies of HIV - human immunodeficiency virus - but they were unlike any seen before, leading researchers to suspect that it was a previously unknown strain of the virus.

Their suspicions proved correct. "The strain has genetic segments from three subtypes, rather like the combined strands of DNA seen in people of mixed race," said Zheng Yongtang, from the Kunming Institute of Zoology at the Chinese Academy of Sciences, whose team conducted the research.

"Currently, we have no idea how dangerous the new strain is, because the research was based on analysis of ribonucleic acid in the blood, but the strain itself has not been extracted because of the small amount of blood provided for the test," he said.

In 2011, Zheng's team carried out genetic studies on 105 blood samples collected by the Yunnan International Travel Healthcare Center between 2008 and 2010. All the samples belonged to long-distance truck drivers from outside China, mainly from Myanmar.

Sample No 11 was the only one that carried the new strain, which was described as "one of the most complicated strains of HIV-1 ever detected in Myanmar - a recombinant (mix) of three different HIV subtypes", in a recent article in the journal AIDS Research and Human Retroviruses.

http://yunnan.chinadaily.com.cn/puer/2015-09/16/content_21895762.htm
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Original E-mail I sent to researchers: 

On Jul 12, 2017, at 10:18 AM,

Re: HIV hijacks surface molecule to invade cell

What

Researchers at the National Institutes of Health have discovered a key step in the process that HIV uses to inject its genetic material into cells. Working with cultures of cells and tissues, the researchers prevented the invasion process by chemically blocking this step, preventing HIV genetic material from entering cells. The findings could lead to the eventual development of new drugs to prevent HIV infection. The study, appearing in Cell Host & Microbe, was led by Leonid V. Chernomordik, Ph.D., at NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). To infect a cell, a protein on the surface of HIV binds to molecules on the cell’s surface. This binding process initiates a sequence of events that ends with HIV’s outer membrane fusing with the cell’s membrane. The virus’ genetic material then passes into the cell. The researchers discovered that the binding process activates a protein, called TMEM 16F, that transfers another molecule inside the cell membrane, phosphatidylserine, to the membrane’s outer surface. They believe molecules in the viral membrane bind with the exposed phosphatidylserine on the cell surface to enhance the virus’ fusion to the cell. The researchers found that blocking the transfer of phosphatidylserine to the cell surface — or attaching another molecule to phosphatidylserine so it can’t bind with HIV — prevents the virus from infecting the cell. Theoretically, developing drugs that could block each of these steps could provide the basis for treatments to prevent HIV from infecting cells, but much more research is needed. https://www.nih.gov/news-events/news-releases/hiv-hijacks-surface-molecule-invade-cell
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This is another e-mail I sent to a researcher explaining what I found while researching HIV vaccine trials:

Sent: Thursday, August 11, 2016 12:20 PM
To: xxxxx

Subject: Make sure to save and read this. compares where and when HIV vax and JE- mouse vaccines happened -Look at table 1 on the 2nd page attached - history of all HIV vaccines - this is from pdf " 30 years of vaccines"

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494212/

start on page 2 of attached pdf it shows all HIV vaccine trials first was in 1986, first US trial 1988: 2. A Very Brief History of the Global Effort to Develop an HIV Vaccine

They started a global group HVTN http://www.hvtn.org/en/about/hvtn-governance.html

As required under our cooperative agreement with DAIDS, the HVTN has established bylaws for the Network. Started 1986 DAIDS: http://www.niaid.nih.gov/about/organization/daids/Pages/default.aspx

These links above also show the sites for the vaccine trials. Fauci did the phase 3 trial HIV vax in the US and China in 1993 and in Thailand in 1994 ( and this is the one he also did in 2003 in Thailand again where he combined 2 vaccines as some of the previous ones did not work from Vaxgen. https://en.wikipedia.org/wiki/RV_144 and the RV 144 is the one in clinical trials in Africa now (the canadians have one too in phase 3 trials and being manufactured in the US as we speak).

JE vax info: http://www.who.int/immunization/policy/position_papers/pp_je_feb2015_refs.pdf

I compared and in 1989 they gave 120 million children in China a 3 shot series of JE -vera shots at age 1, 2 and 6. Although this vaccine was the vera one they passaged it in hamsters kidneys and 3 times through mice during production and said they also used the skin and the spleen for further passage. Thailand and Japan got the mouse brain versions in 1986, 1988,1989. Western subjects got mouse braind US, uk during 1983 through 1990. Taiwan and Thailand thousands got JE-MB fro 1965 then in 1984-85. The JE VAX (Biken) is Mouse brains, as is JE-MB, the SA 14-14-2 is the JE hamster/chicken cells passaged through mic 3 times vax. The tables of the countries or vaccines trials were done is all in the tables starting at table 5 here: THIS ONE IS HIGHLY IMPORTANT http://wonder.cdc.gov/wonder/prevguid/p0000008/p0000008.asp#Table_5
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In 1999 they gave 160,000 doses of JE hamster/mouse passaged to children age 1-15 in 3 districts of Nepal. ( US servicemen got the JE vax in 1990-1991 and in the 80's and at other times throughout the years and it shows all on that CDC table document)

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What Has 30 Years of HIV Vaccine Research Taught Us?

Abstract

When HIV was discovered and established as the cause of AIDS in 1983–1984, many people believed that a vaccine would be rapidly developed. However, 30 years have passed and we are still struggling to develop an elusive vaccine. In trying to achieve that goal, different scientific paradigms have been explored. Although major progress has been made in understanding the scientific basis for HIV vaccine development, efficacy trials have been critical in moving the field forward. Major lessons learned are: the development of an HIV vaccine is an extremely difficult challenge; the temptation of just following the fashion should be avoided; clinical trials are critical, especially large-scale efficacy trials; HIV vaccine research will require long-term commitment; and sustainable collaborations are needed to accelerate the development of an HIV vaccine. Concrete actions must be implemented with the sense of urgency imposed by the severity of the AIDS epidemic.

1. Introduction

The development of an HIV vaccine has been a long and tortuous process that, thus far, has consumed nearly 30 years of intense laboratory and clinical work. When HIV was discovered and established as the cause of AIDS in 1983–1984 [1], many people believed that a vaccine would be easily developed and rapidly deployed. After all, vaccinologists had been very successful in developing vaccines for a whole range of viral diseases.

However, the paradigm that allowed the development of most existing viral vaccines, which is based on the recreation of the protective immunity that develops after natural infection, does not work in the case of HIV. In AIDS, virus-induced immune responses are not capable of preventing re-infection or are very inefficient in slowing progression to disease.

The history of HIV vaccine development has been a tour de force in trying to develop protective immune responses that nature has not learned to produce. Although we are closer today to an HIV vaccine than we were in 1983, it is not possible to predict when we will have a vaccine with sufficient efficacy for use in public health programs. Nevertheless, if we learn lessons from the past and, most importantly, have the wisdom to apply them, we may be able to accelerate the development of a much needed HIV preventive vaccine.

This article summarizes past efforts made to develop a preventive HIV vaccine. It discusses the insights that have guided those efforts, and identifies lessons that can inform the path forward.

This discussion is based on personal experiences after more than 25 years of involvement in the global HIV vaccine effort. First at the World Health Organization (WHO), and the Joint United Nations Program on AIDS (UNAIDS) in Geneva, Switzerland (from 1986 to 2004), and more recently at the Bill & Melinda Gates Foundation in Seattle, WA, United States (since 2004).

Go to:

2. A Very Brief History of the Global Effort to Develop an HIV Vaccine

I recently reviewed the history of HIV vaccine development [2], and this section presents a summary. Table 1 includes some of the key events in the basic science, clinical trials and organizational fronts.

Table 1

Key events on the history of HIV vaccine research and development.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4494212/

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Original E-mail I sent:

Sent: Sunday, August 7, 2016 8:44 PM

To: xxxxx

Subject: HIV trials in US

this shows the 2 HIV vaccines trials in the US and where they did them https://clinicaltrials.gov/ct2/show/NCT00002402

A Study of AIDSVAX B/B and AIDSVAX B/E, Two Possible ...

clinicaltrials.gov

The purpose of this study is to see if it is safe and effective to give AIDSVAX B/B or AIDSVAX B/E, two potential HIV vaccines, to HIV-negative volunteers.

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E-mail I sent to another on: Sunday, August 7, 2016 9:19 PM

To: xxxxx

Subject: who knew they were doing HIV vaccines in the US in 1998

"Western blot testing of EIA-reactive gp120 vaccine recipients, who currently constitute the largest group of vaccine recipients, yielded only indeterminate results, which indicates that, although these vaccine recipients may be requested to undergo repeat HIV testing, they have a low likelihood of being misclassified asHIV-1 infected."

Does that mean they infected them from the vaccine? the results are found on the clinical trial pages but I think this is the results of the US HIV trials.

Mayer K, Judson F, Gorse G, Harro C, Peterson M, Zaharias E, Good J, Shibata R, Lee S, Eastman D, Chernow M, Francis D, Berman P. A phase I/II trial to evaluate the safety and immunogenicity of the AIDSVAX B/B vaccine in the United States (final report). 8th Conf Retro and Opportun Infect. 2001 Feb 4-8 (abstract no 178)

ClinicalTrials.gov Identifier: NCT00002402 History of Changes Other Study ID Numbers: VAX 002 Study First Received: November 2, 1999 Last Updated: June 23, 2005 Health Authority: United States: Food and Drug Administration

http://jid.oxfordjournals.org/content/187/6/879.full.pdf

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Human Immunodeficiency Virus (HIV) Seropositivity among Uninfected HIV Vaccine Recipients

Marta-Louise Ackers Bharat Parekh Thomas G Evans Phillip BermanSusan Phillips Mary Allen J. Steven McDougal

The Journal of Infectious Diseases, Volume 187, Issue 6, 15 March 2003, Pages 879–886, https://doi.org/10.1086/368169

Published:

15 March 2003

Abstract

Since 1987, >10,000 individuals worldwide have received immunizations with human immunodeficiency virus (HIV) preventive vaccine constructs. Many constructs elicit antibodies detected by standard serologic tests (enzyme immunoassays, rapid tests, and Western blots) and result in vaccine recipients’ serum being identified as reactive and indicative of HIV infection. To determine the frequency of vaccine-induced HIV antibody among uninfected HIV vaccine trial participants and to identify factors associated with these results, serum samples from HIV-uninfected participants from selected United States phase I/II HIV-1 vaccine trials were tested with 6 serologic screening tests. Reactive specimens were tested by use of Western blot. Overall, 490 serum specimens from 461 vaccine recipients were tested; 100 (20.4%) reacted on at least 1 serologic test, and 65 (13%) were determined to be positive by Western blot. Canarypox or vaccinia vaccine recipients’ serum with or without HIV envelope glycoprotein (gp120 or gp160) boosts accounted for all positive Western blot results; no positive Western blot results were obtained from gp120 subunit recipients. The potential for vaccine recipients being misclassified as HIV infected increased with vaccine complexity.

SubjectsFrom February 1988 to May 2000, the National Institutes of Health–sponsored AIDS Vaccine Evaluation Group (AVEG) conducted >50 phase I HIV-1 vaccine trials (comprising 35 linked studies) in the United States [13]. Six of these phase I trials involved 562 participants and were conducted between 1993 and 1998. In addition, from 1997 through 1999, VaxGen (Brisbane, CA) conducted a HIV-1 phase I/II vaccine trial among 120 US participants. All 682 vaccine participants were healthy individuals, aged 18–60 years, generally assessed to be at low risk for HIV exposure (although 1 AVEG trial enrolled persons at higher risk for HIV infection through sexual or injection drug use exposure [14]), enrolled at 8 US clinical trial sites in major metropolitan areas, and negative for HIV-1 by EIA at the time of enrollment. In 4 of the 6 AVEG trials, participants also were required to be negative for HIV-1 by Western blot upon enrollment

Vaccine constructs and study regimensThree types of HIV-1 vaccine constructs were evaluated in the 6 AVEG trials that are described here: (1) the recombinant protein subunit rgp120 SF-2 combined with MF59, an oil-in-water adjuvant (Chiron); (2) TBC-3B (a live, recombinant vaccinia virus expressing the env and gag/pol genes of HIV-1 strain IIIB, grown in African green monkey kidney cells; Therion Biologics) administered through 1 of 3 routes (scarification, intradermal, and subcutaneous) followed by boosts of 300 μg rgp120 MN (VaxGen); and (3) 5 ALVAC recombinant canarypox constructs (vCP125 [gp160], vCP205 [gp120, gp41, gag, and protease], vCP300 and vCP1433 [vCP205 with additional sequences from pol and nef], and vCP1452 [vCP205, with additional sequences from pol and nef, and 2 vaccinia virus coding sequences]) (Pasteur Merieux/Connaught [now Aventis Pasteur]), alone or with rgp120 SF-2 priming or boosts or rgp160MN/LAI boosts (Pasteur Merieux/Connaught). Control preparations included the following: an ALVAC recombinant canarypox expressing the rabies glycoprotein (vCP65) with or without rgp120 SF-2 priming or boosts and the formerly licensed vaccinia vaccine (DryVax; Wyeth Laboratories). Studies included 4–6 immunizations administered over 3–12 months, and serum specimens were collected from participants before and after each vaccination, to evaluate the safety, toxicity, and immunogenicity of the vaccine constructs. During the AVEG trials, HIV infection was excluded from these participants’ specimens by use of algorithms that included serologic and nucleic acid–based tests and culture. Details of the study designs have been reported elsewhere [13] The VaxGen phase I/II vaccine trial (VAX 002) evaluated a recombinant protein subunit vaccine, rgp120, in 2 bivalent formulations: AIDSVAX B/B containing MN rgp120/HIV-1 and GNE8 rgp120/HIV-1, and AIDSVAX B/E containing MN rgp120/HIV-1 and A244 rgp120/HIV-1 in an aluminum hydroxide adjuvant. Thirty participants received 300 μg of each antigen (B and E), and 90 participants were randomly assigned to 1 of 3 different B/B study groups (100, 300, or 600 μg). There was no placebo group. All participants received 4 doses over 12 months. Serum specimens were collected from participants at enrollment, before and 2 weeks after each immunization, and at study conclusion [15, 16]

https://doi.org/10.1086/368169
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E-mail I sent to another: Wednesday, June 7, 2017 9:03 PM

Xenotropic Murine leukemia related virus (XMRV) in Iranian

HIV Patients

Vasefi SN1, Bokharaei-Salim F1, Tavakoli A1, Keyvani H1, Farahmand M2, Mortazavi HS1, Monavari SHR1*

1. Department of Virology, Iran University of Medical Sciences, Tehran, Iran

2. Department of Virology, Tehran University of Medical Sciences, Tehran, Iran

https://www.researchgate.net/profile/Ahmad_Tavakoli4/publication/317224666_Xenotropic_Murine_leukemia_related_virus_XMRV_in_Iranian_HIV_Patients/links/592c7236aca27295a8148e6d/Xenotropic-Murine-leukemia-related-virus-XMRV-in-Iranian-HIV-Patients.pdf

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This was a researcher who was
This is an e-mail I sent to another on: Sat 8/27/2016 2:27 PM

Here is a document and letters to Fauci and Varmus asking them to stop the VLP HIV vaccine trials: Dr. Veljko Veljkovic Laboratory of Multidisciplinary Research Institute for Nuclear Scicnces - response to your rcquests to Dr. Anthony Fauci and rne for comments on your article entitled 'Molecular Basis of the Inefficacy and Possible Harmful effects of AIDS Vaccine candidates Bascd on HIV-1 Envelope Glycoprotein gpl20.   Here is Dr. Veljko Veljkovic's letter of concerns:

http://web.archive.org/web/20030122171545/http://www.newstrolls.com/news/dev/CJ/vaccine/103098.htm

Here were the responses:

http://web.archive.org/web/19990501233900/http://www.newstrolls.com/news/dev/CJ/vaccine/letters.htm

So the VLP technology Fauci used for the first HIV vaccines were in 1988. You can see they were testing this in mouse facilities:

1988 Initial description of R5 and X4 virus phenotypes.First HIV vaccine trial in the US (recombinant gp160, MicroGeneSys); Second HIV vaccine trial in the US (gp160 in a vaccinia vector, BMS/Oncogen).

http://www.hiv.lanl.gov/content/immunology/pdf/1999/1/tables/gp160.pdf

CTL - HIV Databases
www.hiv.lanl.gov
HIV CTL Epitopes CTL I-A-83 DEC 99 HXB2 Location Author Location Sequence Immunogen Species(HLA) References gp160(33–42) Env(32–41 Clade B) KLWVTVYYGV HIV-1 ...
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E-mail I sent to another on Tue 8/16/2016 6:33 PM

In 1988 they did the first US and China HIV vaccine study using this gp160. Which was genetically engineered into a VLP. In fact they went on to make 3 VLP versions of HIV vaccines. The next trial see below was done on HIV infected children in 1993. This is what they used and did: In 1993 they did the first nationwide HIV infected "children" vaccination trial using 3 different vaccines.

"The trial will test two doses each of three experimental vaccines made from recombinant HIV proteins. These so-called subunit vaccines, each genetically engineered to contain only a piece of the virus, have so far proved well-tolerated in ongoing trials in HIV-infected adults.
One vaccine made by MicroGeneSys Inc. of Meriden, Conn., contains gp160 -- a protein that gives rise to HIV's surface proteins -- plus alum adjuvant. Adjuvants boost specific immune responses to a vaccine. Presently, alum is the only adjuvant used in human vaccines licensed by the Food and Drug Administration.
Both of the other vaccines -- one made by Genentech Inc. of South San Francisco and the other by Biocine, a joint venture of Chiron and CIBA-Geigy, in Emeryville, Calif. -- contain the major HIV surface protein, gp120, plus adjuvant. The Genentech vaccine contains alum, while the Biocine vaccine contains MF59, an experimental adjuvant that has proved safe and effective in other Phase I vaccine trials in adults.
A low dose of each product will be tested first against a placebo in 15 children. Twelve children will be assigned at random to be immunized with the experimental vaccine, and three children will be given adjuvant alone, considered the placebo. Neither the health care workers nor the children will be told what they receive.

One of the vaccines https://aidsinfo.nih.gov/news/19/first-hiv-vaccine-therapy-trial-begins-in-hiv-infected-children

many trials to include this 1993 are done by this group funded by NIAID and used ALVAC which is: RECOMBINANT ENVELOPE PROTEINS OF HIV1/GP160 https://actgnetwork.org/about-actg

Another HIV vax they used in trials was gp120 which was genetically engineered to make "Virus Like Particles" See here and attached: http://jvi.asm.org/content/66/7/4003.full.pdf
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These were the VLP’s Vaccines

https://aidsinfo.nih.gov/news/187/niaid-launches-three-new-aids-vaccine-trials

NIAID Launches Three New AIDS Vaccine Trials

Date: June 13, 1995
Source: National Institutes of Health (NIH)
Author: National Institute of Allergy and Infectious Diseases (NIAID)

Three new trials of experimental vaccines to prevent HIV infection or AIDS recently began enrolling 144 total needed volunteers, the National Institute of Allergy and Infectious Diseases (NIAID) announced.

Volunteers are being recruited through NIAID's AIDS Vaccine Evaluation Group (AVEG), which consists of six clinical units located in St. Louis, Nashville, Seattle, Birmingham, Baltimore and Rochester (N.Y.).

These new trials are among the 23 trials of 16 preventive AIDS vaccines NIAID has sponsored since 1988. "NIAID is committed to advancing the best candidate HIV vaccines into the testing pipeline," says Anthony S. Fauci, M.D., the Institute director, "and we appreciate the contribution of the nearly 1,700 non-HIV-infected healthy men and women who have volunteered for these trials so far."
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First VLP Vaccines- HIV

Expression and characterization of genetically engineered human immunodeficiency virus-like particles containing modified envelope glycoproteins: Implications for development of a cross-protective AIDS vaccine

Article in Journal of Virology 66(7):4003-12 · August 1992 with 6 Reads

Abstract
Noninfectious human immunodeficiency virus type 1 (HIV-1) viruslike particles containing chimeric envelope glycoproteins were expressed in mammalian cells by using inducible promoters. We engineered four expression vectors in which a synthetic oligomer encoding gp120 residues 306 to 328 (amino acids YNKRKRIHIGP GRAFYTTKNIIG) from the V3 loop of the MN viral isolate was inserted at various positions within the endogenous HIV-1LAI env gene. Expression studies revealed that insertion of the heterologous V3(MN) loop segment at two different locations within the conserved region 2 (C2) of gp120, either 173 or 242 residues away from the N terminus of the mature subunit, resulted in the secretion of fully assembled HIV-like particles containing chimeric LAI/MN envelope glycoproteins. Both V3 loop epitopes were recognized by loop-specific neutralizing antibodies. However, insertion of the V3(MN) loop segment into other regions of gp120 led to the production of envelope-deficient viruslike particles. Immunization with HIV-like particles containing chimeric envelope proteins induced specific antibody responses against both the autologous and heterologous V3 loop epitopes, including cross-neutralizing antibodies against the HIV-1LAI and HIV-1MN isolates. This study, therefore, demonstrates the feasibility of genetically engineering optimized HIV-like particles capable of eliciting cross-neutralizing antibodies.
https://www.researchgate.net/publication/21552263_Expression_and_characterization_of_genetically_engineered_human_immunodeficiency_virus-like_particles_containing_modified_envelope_glycoproteins_Implications_for_development_of_a_cross-protective_AIDS
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E-mail sent to another on:

Sent: Sunday, August 7, 2016 8:44 PM

Subject: HIV trials in US

this shows the 2 HIV vaccines trials in the US and where they did them https://clinicaltrials.gov/ct2/show/NCT00002402

A Study of AIDSVAX B/B and AIDSVAX B/E, Two Possible ...
clinicaltrials.gov
The purpose of this study is to see if it is safe and effective to give AIDSVAX B/B or AIDSVAX B/E, two potential HIV vaccines, to HIV-negative volunteers.

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I sent this is an e-mail to researchers and others on: Sent: Monday, October 16, 2017 1:33 PM

'Mosaic' HIV Vaccine Looks Good In Early Trial, Boston Researcher Tells AIDS Conference →
July 26, 2017

By Carey Goldberg
wbur July 26th, 2017

At a major international AIDS conference in Paris this week, researchers presented findings on a new HIV vaccine that look promising enough to launch a big clinical trial by the end of this year. That means it's still several years before the vaccine could come into widespread use, and that's in a best-case scenario. But still, in the monumentally frustrating world of HIV vaccines — or rather, the lack thereof — any good news is excellent news.

I spoke with Dr. Dan Barouch, professor of medicine at Beth Israel Deaconess Medical Center and Harvard Medical School, who is leading the research. Our conversation, edited:

How would you sum up what you're presenting?

We are presenting the phase 1 and phase 2a clinical data on a new HIV vaccine concept. We've been working on this vaccine together with [the company] Janssen as well as multiple other partners, and our goal is to create a global HIV vaccine, using optimized, so-called 'mosaic' HIV sequences, delivered by a common cold virus, and then boosted by a purified protein to augment antibody titers.

In pre-clinical studies in rhesus monkeys, this vaccine provided 66 percent protection against a series of virus challenges. We've now advanced this vaccine into clinical trials, and in the phase 2a clinical study, called APPROACH, we enrolled 393 participants in the United States, East Africa, South Africa and Thailand. To date, the vaccine has been shown to be safe, and has induced robust immune responses in human volunteers, including 100 percent of vaccine recipients developing antibody responses.

Importantly, the responses induced in humans were essentially comparable with the responses that we believe were protective in animals. So these findings support the advancement of this vaccine candidate into a larger phase 2b efficacy trial, which we hope will begin before the end of 2017.

What is the difference between a phase 2a and 2b study?

A phase 2a study is a study typically in several hundred people, and the goal is to evaluate the safety of the vaccine as well as whether the vaccine induces immune responses that were intended. A phase 2b study is the first study to actually look at the efficacy of the vaccine: Does the vaccine actually prevent HIV infection in humans? That is a much larger study, typically several thousand people. It will probably take about three years.

What do you what do you mean by 'mosaic' and why does that seem to be the approach to take?

In a collaboration between our group and Los Alamos National Labs, we developed synthetic HIV sequences that are not the full sequences found in any virus in real life, but rather are computer-optimized sequences that encode the sequences that we believe will raise immune responses that are most relevant for globally circulating viruses.

HIV is a hugely diverse virus, and one of the big challenges in the development of an HIV vaccine is the diversity of the virus worldwide. We believe that these sequences will likely raise immune responses that are the best we can do now to cover this global diversity of the virus.

How effective would you expect this vaccine to be in humans?

That's an incredibly important question. We don't yet know whether this vaccine will be effective in humans, and if so, we don't know the extent. That's the goal of the next phase of testing. So it's really not possible to predict at this time how effective it will be in humans. But I would say that the pre-clinical and early-phase clinical data to date are promising, and contribute, I think, to a new sense of optimism that the development of a safe and effective HIV vaccine might in fact be possible.

Is this a 'first' or a 'most'?

There have only been four HIV vaccine concepts that have been tested for clinical efficacy in humans to date. There have been many other vaccines that have been tested in small studies or animal studies, but only four concepts have advanced to the point of testing for whether they actually prevent HIV infection in humans.

So assuming that further data generated this fall continues to look good, then we'll be in a position to start the efficacy trial of this vaccine concept before the end of this calendar year. So it is a test of a new vaccine concept. And in animal models, the data looks promising. And in the early phase clinical trials, the data also looks promising.

Where will the efficacy trial be conducted?

The trial will be conducted in sub-Saharan Africa: in South Africa as well as a number of other countries in sub-Saharan Africa.

Why has developing an HIV vaccine been so very, very hard, and how might this be an answer that could address that difficulty?

The challenges in the development of an HIV vaccine are unprecedented in the history of vaccineology. Never before has a vaccine had to handle the challenges posed to it by HIV. I'll just give you two examples. The first example is virus diversity. We need a new flu vaccine every year. The diversity for HIV is vastly more than influenza. So if you need a different flu vaccine every year, how are you going to make an HIV vaccine that covers the genetic diversity of the virus worldwide? So, an attempt to solve that problem is the generation of these synthetic, so-called mosaic sequences that aim to expand the breadth of immune responses that are induced by the vaccine.

A second major problem is that HIV integrates into host chromosomes very quickly and creates long-lived latent reservoirs; essentially, the viruses quickly go into some cells and go to sleep. Those are exceedingly difficult to eradicate. So for a vaccine to be successful, the virus has to be blocked before it can establish latency. So not only would a vaccine have to induce a broad variety of immune responses that can handle the genetic diversity of the virus, but those immune responses have to be potent and powerful enough to act very, very quickly upon exposure to the virus.

And could you explain a little more the joint effort to computer-generate the sequences that you that you needed?

In a collaboration with Bette Korber at Los Alamos National Labs, we looked at virus sequences from all over the world. And those were used to create synthetic antigens that are not found in nature but rather are computer-based approximation of the sequences that would give the optimal coverage of global viruses. And so these antigens — we showed first in monkeys as well as in humans now — can raise robust immune responses to HIV.

I should emphasize that we do not yet know whether this vaccine will protect humans but I think the data to date are encouraging enough to advance this vaccine candidate forward into larger scale testing.

If this pans out, will this be the first vaccine developed in that way?

Yes. This would be the first vaccine developed in that way that will have advanced into efficacy trials.

Are there other applications for this approach if it works?

There could be lessons for the generation of vaccines for other diverse pathogens as well.

http://cvvr.hms.harvard.edu/blog/http/wwwwburorg/commonhealth/2017/07/26/mosaic-hiv-vaccine?fbclid=IwAR00vfOvxzA3mk7OxpwZeOB50YRRFCILoUXTi2GjM5s8n2tViM7qphEWL0k

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I sent this e-mail to researchers and others on: Mon 10/2/2017 8:35 AM

I asked this: Have you seen this? HIV Mosaic multi strain HIV delivered with a vector?

Their answer: "no did not see"

https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-encouraging-first-in-human-clinical-data-for-investigational-hiv-preventive-vaccine

Johnson & Johnson Announces Encouraging First-in-Human ...
www.jnj.com
In Phase 1/2a APPROACH study, HIV-1 antibody response observed in all healthy volunteers Mosaic-based vaccine regimen is designed to elicit an immune response against ...

INNOVATIONJohnson & Johnson Announces Encouraging First-in-Human Clinical Data for Investigational HIV Preventive Vaccine

In Phase 1/2a APPROACH study, HIV-1 antibody response observed in all healthy volunteers

Mosaic-based vaccine regimen is designed to elicit an immune response against a wide variety of HIV subtypes prevalent worldwide

Positive clinical and preclinical results inform selection of lead mosaic HIV vaccine regimen for further evaluation in Phase 2b proof-of-concept study

Paris, France, 24 July 2017 – Johnson & Johnson today announced encouraging first-in-human clinical data for an investigational HIV-1 vaccine regimen in development at its Janssen Pharmaceutical Companies. In an oral presentation of the early stage Phase 1/2a APPROACH study at the 9th IAS Conference on HIV Science (IAS 2017), the “mosaic”-based vaccine regimen from Janssen Vaccines & Prevention B.V. (Janssen) appeared to be well-tolerated and elicited HIV-1 antibody responses in 100% of healthy volunteers (n=393).

“Finding a preventive vaccine has proven to be one of the biggest scientific challenges in the 35-year quest to end the HIV pandemic. A successful preventive vaccine for HIV will need to provide broad protection against a wide range of viral strains,” said Professor Dan Barouch, Harvard Medical School, Director of the Center for Virology and Vaccine Research at Beth Israel Deaconess Medical Center and a key collaborator for APPROACH. “These promising, early-stage results suggest that these vaccines utilizing mosaic immunogens should be evaluated further for their potential ability to achieve this historic goal.”

Significant progress has been made in the global battle against HIV/AIDS, including the development of critical antiretroviral treatments and HIV prevention tools, yet the disease remains one of the greatest global health threats of our time. An estimated 37 million people are currently living with HIV-1 globally, and nearly 2 million people become newly infected each year. An effective HIV vaccine is elusive due to the unique properties of the virus – including its genetic diversity and ability to mutate rapidly.

Mosaic-based vaccines contain immunogens created using genes from different HIV subtypes responsible for HIV-1 infections worldwide. These immunogens are delivered through viral vectors, including Janssen’s AdVac® technology based on adenovirus serotype 26 (Ad26). The viral vectors are combined with other components such as soluble proteins to form mosaic-based prime-boost vaccine regimens that first prime and then boost the immune system, with the aim of producing stronger and longer-lasting immunity to HIV.

Paul Stoffels, M.D., Chief Scientific Officer, Johnson & Johnson said, “In recent years, a new optimism has emerged that we will find an effective HIV vaccine in our lifetime. The results from today’s study add to that belief and we look forward to advancing to the next stage of clinical development as quickly as possible.”

In pre-clinical studies, regimens incorporating mosaic vaccines demonstrated protection against infection with an HIV-like virus. The most effective prime-boost regimen in these studies reduced the per-exposure risk of infection by 94 percent and resulted in 66 percent complete protection after six exposures.

Based on immunologic responses observed in APPROACH, as well as protection observed in pre-clinical studies, a lead HIV-1 vaccine regimen comprising Janssen’s Ad26 mosaic candidate and the Clade C gp140 soluble protein has been selected as the basis for further evaluation in a potential Phase 2b proof-of-concept efficacy study. Should this study move forward, Janssen and its global partners anticipate initiating this investigation in southern African countries in late 2017 or early 2018.

About the APPROACH Study
APPROACH (HIV-V-A004/NCT02315703) is a multi-center, randomized, parallel-group, placebo-controlled, double-blind Phase 1/2a study in 393 healthy HIV-uninfected adults in the US, Rwanda, Uganda, South Africa and Thailand. It is evaluating the safety, tolerability and immunogenicity of various mosaic-based, prime-boost vaccine regimens for HIV-1. These vaccine regimens contain two prime doses of the mosaic viral vector Ad26.Mos.HIV and two boosts of either Ad26.Mos.HIV, MVA-Mosaic and/or different doses of the soluble protein Clade C gp140 adjuvanted with aluminum phosphate. Vaccination schedules have been completed for all study participants and 12-month follow-up after the 4th dose is underway.

Results presented at IAS 2017 suggest that all vaccine regimens appeared to be well-tolerated. Injection site pain, headache and fatigue were the most common reported adverse events. The primary analysis post 3rd vaccination showed that most active vaccine regimens elicited antibody responses in 100% of study participants. Antibody titers against autologous Clade C and heterologous cross-clade Env antigens increased in groups boosted with gp140 protein, irrespective of vector. After the 4th vaccination, humoral and cellular responses further increased.

The APPROACH study was sponsored by Janssen with support from partner organizations including Beth Israel Deaconess Medical Center (BIDMC); the United States Military HIV Research Program (MHRP) at the Walter Reed Army Institute of Research (WRAIR), with the Henry M. Jackson Foundation for the Advancement of Military Medicine (HJF); the National Institute of Allergy and Infectious Diseases (NIAID), part of the US National Institutes of Health (NIH); the Ragon Institute; the International AIDS Vaccine Initiative (IAVI); and the HIV Vaccine Trials Network (HVTN).

About Janssen’s HIV Preventive Vaccine
Janssen’s HIV-1 AdVac®-based vaccine regimen, along with the company’s investigational Ebola and inactivated polio vaccine candidates, utilize Janssen’s PER.C6® production cell line technology, which has the potential to reduce costs by increasing vaccine production at lower reactor volume.

Since 2005, Janssen Vaccines & Prevention B.V. has been participating in the NIH-supported Integrated Preclinical/Clinical AIDS Vaccine Development (IPCAVD) program under grants AI066305, AI078526 and AI096040. Janssen’s HIV vaccine program has also received funding from the United States Military HIV Research Program and the Ragon Institute..... https://www.jnj.com/media-center/press-releases/johnson-johnson-announces-encouraging-first-in-human-clinical-data-for-investigational-hiv-preventive-vaccine

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Johnson & Johnson is about to test an experimental HIV vaccine on thousands of people

By JOHN LAUERMAN
| BLOOMBERG |
JUL 12, 2019 | 9:35 AM

Johnson & Johnson is preparing to test an experimental HIV vaccine in the United States and Europe in a move toward developing the first immunization against the deadly disease after decades of frustration.

Some 3,800 men who have sex with men will receive a regimen of shots in a study that is planned to be launched this year, said Anthony Fauci, director of the U.S. National Institute of Allergy and Infectious Diseases. The agency and the HIV Vaccine Trials Network of testing sites are to collaborate with J&J’s Janssen unit on the effort.

Since cases began to gain notice in the early 1980s, scientists have been searching fruitlessly for a vaccine against the virus that causes AIDS and kills close to 1 million people worldwide each year. Efforts are continuing, with at least two other promising candidates in late-stage studies.

J&J is trying to make a vaccine that will work in populations around the world that are infected with myriad strains of the rapidly changing virus. Other candidate shots have focused on preventing single varieties.

The approach “brings us one step closer to covering the vast diversity of viruses worldwide,” said Dan Barouch, a Harvard Medical School professor whose research laid the groundwork for the vaccine. “For medical and global public health reasons, it’s better to have a vaccine that works in multiple parts of the world.”

Collaborators on the study include the U.S. Army Medical Materiel Development Activity, which develops protective products for soldiers, and results are expected as soon as 2023. The company has spent hundreds of millions of dollars, working with the National Institutes of Health, the Gates Foundation and other groups to try to develop an effective vaccine.

“The cost of treating HIV patients — the burden for patients, the burden for society — is very high,” said Paul Stoffels, J&J’s chief scientific officer. HIV prevention is “a big mission for us. We’ve been working on it for almost 30 years.”

The World Health Organization has set a goal of cutting global HIV-related deaths to less than half a million by next year, and a vaccine is seen as a crucial tool to help end the AIDS epidemic by 2030. Yet efforts to develop a vaccine have been frustrated in part because the virus mutates so quickly.

Vaccine boost

J&J’s vaccine has four components that target multiple strains of HIV, and Barouch has been developing it for about 15 years. He and Bette Korber, a computational biologist at Los Alamos National Laboratory, designed an optimized set of “mosaic” proteins to go in the vaccine that would raise immune defenses against a wide variety of strains.

The vaccine uses a cold virus that is altered to make the proteins that raise immunity. Study participants get six shots in four sessions.

“Conceptually it’s an interesting idea,” Fauci said. “There’s always excitement, but it should be saved for the results.”

Along with the diversity of strains, HIV presents a number of obstacles to vaccination. Reservoirs of the virus can accumulate within certain cells, undetected by the immune system. No one has been able to fashion a vaccine that brings forth broadly neutralizing antibodies, the body’s most effective protection against viruses.

https://www.latimes.com/business/la-fi-hiv-vaccine-johnson-johnson-experimental-20190712-story.html?fbclid=IwAR20x0Hgn34F6JU8Jio2AGXCfYN4J3aUEApfWPKYcvGmbXjNUHbNq72MEjo

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My story and why I became involved in the study of XMRV/MLV retroviruses and other associated areas of research

My Path  Psalm 119:105  105 Your word is a lamp for my feet, a light on my path.  ...