The 7.5-million grant from the NIH National Institute of Allergy and Infectious Diseases will help researchers pinpoint specific factors that lead to a better immune response through HIV vaccination.
CHAPEL HILL, N.C. – Kristina de Paris, PhD, professor in the Department of Microbiology and Immunology, and colleagues were awarded a grant for their project entitled “Determinants of HIV broadly-neutralizing antibody precursor induction in infants.”
The grant, sponsored by the NIH National Institute of Allergy and Infectious Diseases (NIAID), will provide them with $7.5 million in funding over the next five years.
Using the grant, the research team will study changes in the infant rhesus macaque’s antibody response after receiving different HIV vaccine components called adjuvants. They will also be studying the interactions between host immunity and naturally occurring bacteria in the microbiome, in response to vaccination.
“Our goal is to identify innate and microbial factors that impact B cell lineage selection and maturation after vaccination,” said de Paris.
De Paris will be collaborating with Permar from Cornell University, Surana from Duke University, and van Gils from the University of Amsterdam to perform the study.
The human immunodeficiency virus (HIV) is a retrovirus that has numerous strains, or variants, across the world. Once the virus has infected a person, it integrates into the host’s DNA, allowing it to continue to circulate in a dormant state in the host.
When we become infected with a virus, our immune systems respond by producing neutralizing antibodies that can recognize the virus’s primary surface protein. Broadly-neutralizing antibodies, or bNAbs, are specific antibodies that can recognize numerous different strains; however, they are only produced by a small percentage of infected individuals.
A universal HIV vaccine should, in theory, be able to trigger bNAbs, which could then neutralize all strains of the virus that are circulating in the body. Although HIV researchers have attempted to replicate body’s bNAb response through vaccination, few strategies have been successful. According to De Paris, bNAbs are challenging to induce in adults because they are only created by rare mutations in B cells and take many years to develop.
“Chances are low that the early B cells will eventually produce these partly neutralizing antibodies,” said de Paris. “It’s like one in a million. We need to design a vaccine immunogen that can engage the original B cell receptor and cause it to undergo additional mutations to develop that kind of breadth.”
While bNAbs take years to develop in adults, research has repeatedly shown that infants with HIV can develop bNAbs as early as one year post-infection – and at higher rates. De Paris and colleagues hypothesize that the infant’s developing immune system and microbiome could be playing a hand in their formidable antibody response.
Post-birth, infants are only just establishing their microbiomes and their immune systems. A number of factors, including breastfeeding and malnutrition, can impact the microbiota, which, in turn, impacts the development of the immune system.
“We are suggesting that the microbiota, through its interaction with the adjuvanted vaccine, could be facilitating the development of bNAbs, and that there might be specific microbial species that are more helpful at promoting certain immune responses than others,” said De Paris.
To gain such insights, De Paris will be working with experts in HIV vaccine immunology, transcriptomics, BCR sequencing, microbiome and metagenomics, and in statistical analysis and bioinformatics to study the effects of the HIV envelope trimer BG505 GT1.1 vaccine in infant rhesus macaques.
Starting HIV vaccination in early life would also provide the necessary time for the maturation of these bNAbs, so that by the time adolescence is reached, protective bNAbs would prevent HIV infection. Teenagers and young adults account for most new infections.
In future studies, they hope to take advantage of these factors to optimize HIV vaccine strategies and may be able to one day screen vaccine candidates for the potential of bNAb development in human clinical trials.
Media contact: Kendall Daniels, Communications Specialist, UNC Health | UNC School of Medicine