We know that most cases of HIV transmission occur at the mucosal surfaces of the genitals or the rectum (seeThe Great Barrier, IAVI Report, Mar.-Apr. 2008). What we know less about is the types of antibodies that are best at blocking the virus at those surfaces. Studies have shown that antibodies belonging to a class called IgG1 play a role: passive infusion of such broadly neutralizing anti-HIV antibodies into the blood can protect animals from mucosal challenge.
A large Phase IIb trial testing the safety and efficacy of a DNA/Ad5 prime-boost regimen of two vaccine candidates developed by the Vaccine Research Center (VRC) at the National Institute of Allergy and Infectious Diseases (NIAID) has discontinued immunizations.
When the trial that came to be known as HVTN 505 began in 2009, it had a single endpoint: a decrease in the set point viral load in volunteers who became HIV infected despite vaccination (see Vaccine Briefs, IAVI Report, July-Aug. 2009). Adding protection against infection as an additional endpoint in 2011 resulted in a significant change in enrollment in the HVTN 505 trial. The trial was originally designed to enroll 1,350 circumcised, HIV-uninfected men who have sex with men (MSM) or transgendered women who have sex with men with no pre-existing immunity to adenovirus serotype 5 (Ad5). That is the commonly circulating strain of the cold virus that was used as to construct the vector bearing one of the two vaccine candidates.
It’s probably a bit of an understatement to say vaccine researchers were disappointed yesterday, when they heard about the discontinuation of HVTN 505, a clinical trial that tested the efficacy of a DNA/Ad5 prime-boost vaccine regimen in about 2,500 people. When the trial was stopped, there was no significant difference in HIV infections between those who received the candidate vaccines and the placebo recipients. Beyond that, there was a—statistically insignificant—trend towards more infections among the vaccinated (see previous blog postby Regina McEnery).
As the country grapples with US$85 billion in across-the-board spending cuts, set in motion after a US Congressional committee failed to pass bipartisan federal budget legislation, it is worth remembering how legislators from both sides of the aisle just a decade ago launched one of the largest US humanitarian efforts since the Marshall Plan.
Most sexually transmitted HIV infections are the result of just one transmitted virus, but researchers are still wondering what, if anything, makes such transmitted founder viruses so special. Now, a team led by Beatrice Hahn at the University of Pennsylvania has found that transmitted founder viruses have biological properties that give them an advantage when initiating a new infection (Proc. Natl. Acad. Sci. 2013, doi: 10.1073/pnas.1304288110). The results hold true for subtype B and C viruses, both of which were included in the study.
Our latest issue covers the recent Conference on Retroviruses and Opportunistic Infections (CROI), including news about a functionally cured 30-month-old child, and many antibody-related findings reported at the recent Keystone symposium on HIV vaccines. The topics covered in our news section include a rally against looming cuts to federal funding for health research, and new research that suggests that neutralizing antibodies to the HIV protein Tat could be involved in protection. Enjoy, and let us know what you think!
Through the rhetorical din of the April 8 Rally for Research (see blog), a couple of statistics—shared by Rockefeller University President Marc Tessier-Lavigne—sounded like a tocsin: Annual health-care costs have climbed to reach more than US$8,600 per person over the past decade. But the government’s annual investments in the US National Institutes of Health have hovered at a paltry $100 per person—about 80 times less.
Megan Kane never thought her first post-doc assignment would be a temporary job in science communications.
The Virginia resident, who graduated from Johns Hopkins recently with a Ph.D. in human genetics, had hoped to land a job with an academic or government lab focused on HIV/AIDS. She has a particular interest in long-term nonprogressors—HIV-infected individuals who are able to control HIV for up to a decade or more without ever taking ARVs.
When talk turns to the kind of neutralizing antibodies that can prevent HIV infection, it always revolves around one and just one HIV protein: the Envelope (Env) protein that forms the viral spike. That’s because Env is thought to be the only protein HIV carries on its surface, exposed to antibody targeting.
A functionally cured CROI baby? Check out our latest issue of VAX for more details of this interesting case, which was presented at the 20th Conference on Retroviruses and Opportunistic Infections. The March VAXalso covers therapeutic vaccination and the start of a new AIDS vaccine trial in Africa that employs a novel viral vector.
A few days ago, French researchers published a study showing that some patients who start antiretroviral therapy (ART) early, during acute infection, seem to be able to control HIV after stopping therapy, suggesting that they may be functionally cured (PLoS Pathog. 9, e1003211). But there's a lot more to this story--and IAVI Report covered it all last year. If you'd like to know more about this study, its context and the ongoing debate about how soon ART should be started, check out the article in the September-October issue of our magazine.
You’d think scientists would know all there is to know about the biological effects of a substance that has been used for decades to make vaccines. Well, think again. For one thing, they still haven’t figured out how exactly the humble adjuvant alum works—and this concoction of insoluble aluminum salts has been used for more than 80 years to boost the efficacy of childhood immunizations. And for most of that period, it has been the only adjuvant used in human vaccines.
Researchers have lately found dozens of broadly neutralizing antibodies (bNAbs) in HIV-infected people. Unlike their less capable peers, these relatively rare antibodies can neutralize most circulating HIV strains. But only about 20% of HIV-infected people develop bNAbs. What’s more, compared with their precursors in the germline, bNAbs accumulate a large number of mutations, or unusual structural features, to acquire their impressive breadth and potency—through a process known as affinity maturation that appears, in most cases, to take many years.
For a sizeable number of scientists from the US National Institute of Allergy and Infectious Diseases (NIAID), the 20th Conference on Retroviruses and Opportunistic Infections was over before it began.
The trial known as VOICE—for Vaginal and Oral Interventions to Control the Epidemic—was launched in 2009 to evaluate the efficacy of daily topical and oral antiviral drugs in preventing HIV transmission among high-risk heterosexual women from three African countries.
Much of the recent surge in HIV cure research in the clinical setting has focused on HIV-infected adults. This makes sense, since much of it has been inspired by the celebrated case of Timothy Brown, the so-called “Berlin patient,” who has been free of HIV since he received a stem cell transplant from a donor naturally resistant to HIV.
Most antibody-related talks at the meeting stressed the importance of broadly neutralizing antibodies for protection from HIV infection. But Olga Malykhina from Tom Hope’s lab at Northwestern University said that antibodies that just bind to HIV might be sufficient for preventing infection.
Antibodies continued to be a major theme here at the Keystone Symposia on HIV Vaccines and B Cell Development and Function, when Barney Graham of the National Institute of Allergy and Infectious Diseases (NIAID) at the NIH gave an overview of projects at the NIAID’s Vaccine Research Center that involve passive immunization with broadly neutralizing antibodies (bNAbs). The advantage of passive immunization is clear: There is no wait until a vaccine induces highly affinity matured bNAbs, which can take a long time to develop.