On passive immunization and the effects of gender and BMI on vaccination

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. 

Already, Graham said, VRC researchers have shown that passive immunization with VRC01, one of the broadest and most potent bNAbs identified in recent years, can protect rhesus macaques from virus challenge, adding that VRC01 is now ready to be used in human trials. 

Researchers are also trying to further improve the natural versions of bNAbs (which are usually isolated from HIV-infected people), to make them even more potent. While some of these modified bNAbs are much more potent than the natural versions, there is a price to pay, Graham said: Most of the bNAb modifications result in antibodies that are autoreactive, which means that they recognize the body’s own tissues. (The immune system normally eliminates such antibodies, which is why naturally occurring bNAbs are unlikely to be autoreactive.) 

But not all talk was about antibodies. For example, in a session on human vaccine trials, Glenda Gray from the University of Witwatersrand in South Africa reported the somewhat surprising observation that T-cell responses to vaccines can differ depending on gender and body mass index. An analysis of HIV vaccine trials (mostly ones that use DNA vaccines) showed that women showed better T-cell responses to such vaccines than men, and people with a lower body mass index showed better T-cell responses than people with a higher body mass index. The reasons are unclear, although one commenter in the audience speculated that the BMI observation might have something to do with chronic inflammation in obese people. It’s also unclear whether these differences translate into differences in vaccine efficacy. Still, Gray said, this is something to pay attention to when conducting vaccine trials.