Factors involved with mother-to-child spread of HIV
Understanding how HIV is transmitted from one person to another is a critical step in developing an efficacious vaccine. The transmission project in the Sodora Laboratory focuses on the oral transmission of HIV from mother to child, as well as the host immune factors that may affect HIV acquisition in infants. The foundation of this project is seminal studies from the Sodora Laboratory, evaluating the earliest events following oral HIV transmission; the majority of these studies have utilized the SIV-macaque animal model. Our current studies assess factors that activate the immune system and can impact the transmission of HIV from mothers to babies. One type of immune activation infants are exposed to are the standard vaccine regimens given to protect against a number of infectious diseases, one vaccine of interest is the BCG vaccine, which offers protection against tuberculosis. Our previous work demonstrated that human infants immunized with BCG had increased immune activation of HIV target cells, suggesting that BCG may be resulting in an immune environment that is more permissive to HIV infection. Our ongoing study is to utilize the SIV-macaque model to unravel the immune mechanisms that may impact HIV transmission after BCG vaccination, including an increase in immune activation and an expansion of HIV target cells.
A second ongoing study in the Sodora Laboratory evaluates how different feeding practices may impact HIV transmission in infants. These studies involve evaluating samples from South African infants that are either exclusively breast fed or mixed fed (breast milk and cereal or formula); mixed feeding is associated with an 11-fold increased risk of acquiring HIV transmission. The study is designed to provide mechanistic understanding into this observation that is quite perplexing. Presently, we are evaluating how the introduction of non-breast milk foods to infants could potentially alter HIV-target cells in these South African infants.
The long-term goal of this research is to identify the immune changes at the site of transmission that impact the frequency of a successful transmission event, and to utilize the findings to aid in the development of an HIV vaccine designed to prevent transmission of HIV.
Assessing HIV-induced disease progression
HIV entry into the human population began as a zoonotic transmission, from a different species into humans. In the case of HIV, the SIV virus is naturally found in a number of African monkeys and chimpanzees and likely entered into the human populations during the butchering of the monkey/ape meat. SIV in its natural monkey hosts is very different compared to when it infects humans. Generally, these monkeys do not develop any clinical signs of disease. This is particularly perplexing as the virus is able to replicate at high levels in monkeys, yet somehow, the monkeys have learned to live with this infection. Studying one of these monkey species, sooty mangabeys, the Sodora Laboratory was the first to demonstrate that in addition to being OK with high levels of replication, natural hosts are also able to function just fine with low levels of CD4+ T cells. This was a surprising finding, and Dr. Sodora’s laboratory set out to understand which compensatory mechanisms are in place that allowed mangabeys to immunologically function with very low levels of this key immune cell. What they found was that a understudied immune T cell subset, double-negative T cells, have the potential to compensate for CD4 T cell loss and can provide essential immune functions in sooty mangabeys. These cells are called “Double negative,” because they lack two proteins normally associated with T cell function, CD4 and CD8. What is particularly fascinating with regard to utilizing these cells to compensate for the absence of CD4 cells, is that double-negative T cells are resistant to HIV infection (because they lack the CD4 protein). Currently, our lab focuses on characterizing double-negative T cells in humans and determining the potential of these cells to improve immune responses during HIV infection. We believe that harnessing the full potential of double-negative T cells will assist in the restoration of immune competence and decrease the risk of opportunistic pathogens in HIV-infected patients.