Signature of long-lived HIV-specific memory B-cell lineages

Daniel Muema’s work will contribute to informing how HIV vaccines can be designed to confer long-lasting protection from HIV infection. So far, a licensed effective HIV vaccine does not exist. There are, however, several candidate HIV vaccines in early stages of development, and it will be important to tailor them to give durable immunity that can protect individuals from infection long after vaccination. This is particularly important because most candidate HIV vaccines have in the past been shown to induce short-lived immune responses. 

To understand what it takes to induce HIV immune responses that are persistent, Muema will investigate HIV immune responses in individuals who are living with HIV and have since gone on effective HIV treatment with antiretroviral drugs. When individuals get infected with HIV, their immune system gets exposed to HIV proteins and generates HIV immune responses, similar to those that would be generated upon HIV vaccination. Treatment with antiretroviral drugs leads to suppression of viral loads to undetectable levels. This in turn causes a decay of the immune responses over time, similar to the decay of immune responses that would occur in vaccinated individuals. Muema’s team will study these individuals to first assess the longevity of antibody responses, and B cells that produce such antibodies, after suppression of viremia. They will then determine the special characteristics of few antibody responses and B cells that persist. They will also confirm our findings by similarly studying individuals who received a candidate HIV vaccine. 

This will inform how HIV vaccines can be formulated to maximise the generation of antibody and B cell responses that have a higher likelihood of persisting long after vaccination. Success in this will considerably increase the benefits of the HIV vaccines by eliminating the need for costly and frequent booster vaccinations. It will also increase the chances of protection from infection, thus contributing to the effective control of the HIV epidemic. 

SANTHE is an Africa Health Research Institute (AHRI) flagship programme funded by the Science for Africa Foundation through the DELTAS Africa programme; the Bill & Melinda Gates Foundation; Gilead Sciences Inc.; and the Ragon Institute of Mass General, MIT, and Harvard.