Vaccine and Infectious Disease Division

Quantifying Neutralization

In the hunt for an effective HIV vaccine, elucidating why certain candidates don’t work is important to inform future vaccine development.  Many researchers are focusing on vaccines that aim to elicit large numbers of diverse neutralizing antibodies, immune proteins that bind to and deactivate invading viruses.  This approach is especially challenging for HIV, as the virus is genetically diverse, meaning antibodies that recognize one strain may not recognize another variant, and the virus possesses strategies to mask its surface with molecules that cannot be effectively recognized by antibodies.  Different strains have different masking abilities, so some HIV variants are more susceptible to neutralization than others.

VIDD member Dr. Peter Gilbert and colleagues assessed the level and diversity of neutralization antibodies elicited by one failed HIV candidate vaccine, which contained pieces of the HIV surface protein gp120.  This vaccine elicited strong antibody responses in pre-clinical studies, but failed to provide protection against HIV infection in clinical trials.  To better understand the neutralizing antibody responses to the gp120 vaccine, the researchers took blood samples collected during the trial from 90 vaccine recipients and 30 placebo recipients, mixed them with purified HIV viruses of different strains, and then exposed human cells in petri dishes to this mixture and measured how well the viruses were able to infect the cells using a fluorescent reporter triggered by an HIV protein. 

They found that while HIV strains highly susceptible to neutralization were effectively deactivated by the vaccine, strains with better masking against neutralization were still able to infect the human cells.  In fact, the vaccine-induced antibody response was no better than that seen in HIV positive people a few years after infection.  This detailed description of a neutralizing antibody response to an ineffective HIV vaccine may serve as a useful baseline to compare to future candidate vaccines.

Gilbert P, Wang M, Wrin T, Petropoulos C, Gurwith M, Sinangil F, D'Souza P, Rodriguez-Chavez IR, Decamp A, Giganti M, Berman PW, Self SG, Montefiori DC.  Magnitude and Breadth of a Nonprotective Neutralizing Antibody Response in an Efficacy Trial of a Candidate HIV-1 gp120 Vaccine.  J Infect Dis. 2010 Aug 15;202(4):595-605.