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Wednesday, July 25, 2012

HIV vaccine update AIDS 2012 in Washington DC

"Turning the Tide on Transmission," the Wednesday morning plenary session of the XIX International AIDS Conference in Washington DC, opened with Dr. Barton Haynes, from Duke University Human Vaccine Institute (USA). His presentation, titled "The Way Forward for Development of an HIV-1 Vaccine," was the clearest and most understandable vaccine talk that I have ever heard.

Dr. Haynes pointed out that an HIV vaccine is the cornerstone of an integrated HIV prevention program that supports the emerging strategy "The End of AIDS," and that an effective vaccine has been elusive. The most promising vaccine candidate to date has been the so-called RV 144 vaccine from a field trial in Thailand that offered a 30% protection rate.

He went on to describe some of the laboratory activities that accompany vaccine trials, even if that vaccine candidate was not as effective as desired. In other words, there is something to be learned by studying the immune responses of people who received a vaccine that was less than optimal.

A key point of his discussion involved "immune correlates,' measures of immune response that may serve as predictors of vaccine efficacy.

The other major point of discussion was the role of neutralizing antibodies - the vaccine recipients’ immune response with specific antibodies that can neutralize HIV so effectively that infection is prevented. In the case of the RV144 vaccine, he noted that broad neutralizing antibodies did not occur. The study team speculates that protection from this vaccine occurs by a “non-neutralizing” mechanism such as antibody killing of virus-infected cells.

The problem with vaccine candidates to date is that these vaccines do not elicit a strong enough immune response to prevent infection in most people. At best, 15-20% of people with chronic HIV infection respond with adequate neutralizing antibody.

Moreover, there is a disconnect between HIV replication dynamics and the rate of antibody development. In other words, if HIV infection starts out with one virion, as it replicates, it produces escape virus (mutated virus). The corresponding immune response develops on a different schedule. It would appear that the antibody response to HIV infection is sluggish and is not sufficient to neutralize HIV or flight back, at least in the majority of cases.

Two major events have re-invigorated the field of neutralizing antibody production:
(1) The immune correlates analysis from the RV144 vaccine trial that showed a protective effect related to the induction of IgG antibodies specific to the V1/V2 in the absence of IgA responses against HIV that likely mediated protection through non-neutralizing or weakly-neutralizing mechanisms.
(2) A recently identified a panel of new broadly neutralizing antibodies, that provide clues regarding the viruses vulnerabilities. These neutralizing antibodies mark 4 regions of the viral envelope that represent the viruses “Achilles heel” that if targeted by a vaccine could provide protection from infection.

Therefore, to design a vaccine that can elicit such antibodies, the Duke program has now embarked on a “B cell lineage” targeted vaccine, that attempts to define the mechanism(s) by which the 15% of HIV infected patients are able to induce such protective antibodies by mapping the evolution of B cell lineages over time to design novel vaccines that can induce this type of B cell immunity more rapidly.

The Duke program, in collaboration with investigators world-wide, will develop novel vaccine approaches aimed at accelerating the speed of neutralizing antibody induction, that will hopefully provide protection from HIV infection, a key element to achieving an AIDS free generation.

Haynes, B. The Way Forward For Development of an HIV-1 Vaccine. Session WEPL0101.

Source: Reporting for the PRN News: Bill Valenti, MD