Our Research

HIV Research

Antiretroviral therapy has transformed the HIV/AIDS epidemic. Yet, globally, access to ART is still limited for many vulnerable populations. In 2020 alone, we had 1.5 million new HIV infection, the vast majority in low- and middle-income countries. In the De Paris lab, our HIV research is focused (1) on early live HIV vaccines and (2) on the impact of HIV infection on pregnancy.  

HIV Vaccines

Adolescents (age 14-19 years) and young adults (age 15-24years) continue to represent one of the highest risk group for HIV infection. To decrease HIV-1 transmission in the adolescent age group, an effective vaccine needs to elicit protective immunity during pre-adolescence before this population reaches sexual maturity. Broadly neutralizing antibodies (bnAb), antibodies that can recognize conserved epitopes on the HIV envelope (Env) from distinct clades, have emerged as a key goal in HIV vaccine design. These antibodies, however, only develop after years of HIV infection and in only in a fraction of individuals. Interestingly, infants with HIV develop bnAb faster, more frequently, and these bnAb exhibit lower rates of somatic hypermutation compared to bnAb isolated in adults. These data imply that the infant immune system may provide a more favorable environment for the development of bnAb. Therefore, we are testing whether the introduction of HIV Env vaccines in early life – with potential boosting during childhood – would provide the necessary time and immune conditions to can elicit bnAb responses that could then protect adolescents against HIV infection. Towards this goal, we are exploring HIV Env mRNA vaccines and stabilized germline BCR-targeting HIV Env trimers. We employ numerous immunological techniques to assess phenotype and function of B cells, single cell sequencing to define the BCR repertoire evolution post immunization, and test how modulation of innate responses to the vaccine prime impact vaccine-induced antibody responses.

HIV and Pregnancy

Globally, about 15 million babies are born preterm every year. HIV is a known risk factor for adverse pregnancy outcomes, including preterm birth. In sub-Saharan Africa, the epidemics of HIV and PTB collide. The etiology of PTB is multifactorial, with inflammation being a common component. However, the exact maternal mechanisms underlying sPTB are not well understood. We participate in a large multi-omics project to identify metabolic, microbial, and inflammatory signatures associated with spontaneous preterm birth. Using samples from pregnant women with and without HIV of the Zambian Preterm Birth Prevention Study (ZAPPS) and Improving Pregnancy Outcomes with progesterone (IPOP) trial, we are testing longitudinal changes in the metabolome and vaginal milieu that may inform mechanistic studies into PTB-related causes.

COVID-19 Research

The emergence of the novel coronavirus SARS-CoV-2 in early 2020 – leading to the global pandemic – drastically changed all our lives. In 2020, we started two different projects related to SARS-CoV-2. Early in the pandemic, the risk of severe disease in elderly patients and adults with co-morbidities was well defined while less was known about the impact of SARS-CoV-2 on young children. Our group set out to use our expertise of the infant immune system and early life HIV vaccines to assess the infant response to SARS-CoV-2 vaccines. Many short-term challenge studies were underway due to the urgency of vaccine testing and the emerging nature of the pandemic. However, less was understood about long-term vaccine-mediated protection against SARS-CoV-2 infection, especially as it applied to the pediatric population. We vaccinated two groups of infant rhesus macaques, one with a pre-clinical version of the Moderna vaccine and a second group with a stabilized protein vaccine. We followed these animals for a year and then challenged them with the heterologous Delta variant to evaluate vaccine protection.

In addition to our NHP vaccine study, we collaborate with physicians at Duke to characterize T cell responses of patients with X-linked agammaglobulinemia (XLA). Patients with XLA do not make B cell responses due to a defect in a gene that codes for the protein Bruton tyrosine kinase (BTK). Arrest of B cells in an early developmental stage, prevents XLA subjects from producing antibodies. Therefore,  there was little guidance about these patients receiving the SARS-CoV-2 vaccines. In our study, stimulate processed blood samples from these patients with various SARS-CoV-2 related peptides to determine if they could mount a T-cell mediated immune response.

Non-human Primate Research

Much of the research we do in the De Paris lab uses nonhuman primates, specifically, rhesus macaques, as our model organism. We collaborate with the California National Primate Research Center (CNPRC) at the University of California at Davis for our animal care and housing. The CNPRC is one of seven centers across the country that cares for primates providing invaluable resources for investigators. Scientific research greatly relies on animal models to better understand human physiology and disease. Knowledge gained through animal research has transformed our society and the way we treat disease. Nonhuman primates provide one the best comparisons to humans because of their close genetic relationship. Important for our pediatric disease studies, infant immune development in rhesus macaques is highly similar to that in human infants.