Alexandra Morrison Poster 2025

Dr Alexandra Morrison

UK Health Security Agency, UK

Could new tuberculosis vaccines increase the risk of HIV transmission? Investigations using intravenously delivered BCG vaccine and rectal/vaginal swabs and biopsies in macaques

Poster Abstract

HIV/AIDS results in heightened susceptibility to tuberculosis (TB), where risk increases 20-fold (WHO, 2020). One obstacle in developing an HIV/AIDS vaccine is that immunisation may increase numbers of HIV-target cells, activated CD4 T cells, increasing susceptibility to infection. Due to the dual burden of HIV/AIDS and tuberculosis, this phenomenon should be considered for TB vaccines. Vaccinating for TB protection is thought to be dependent on CD4 T cell responses, and the frequency of these cells increases at mucosal surfaces of the lung after intravenous BCG (Darrah, 2019). Therefore, intravenous BCG is an ideal tool to investigate whether vaccination enriches these cells in the mucosal surfaces of the rectum and vagina. A two-phase study was undertaken to investigate this question.

In phase one we successfully optimised protocols to isolate cells from rectal and vaginal cytobrush swabs, a minimally invasive alternative to biopsies, in cynomolgus macaques and investigated CD4 T cell frequency and phenotype in these locations. In naïve macaques the median proportion of CD4 T cells in rectal swabs that were CCR5+ was 20% and in vaginal swabs was 11%. Cell proportions and phenotypes were observed between swabs, rectal biopsies, and full thickness rectum samples. Phase two utilised protocols at multiple timepoints prior to and after IV BCG vaccination, tracking changes in cell populations at rectal and vaginal surfaces over time. Additionally, blood and bronchoalveolar lavage (BAL) samples were collected and analysed to investigate relationships between mucosal and systemic compartments. Phase two findings will be available from March 2025.

What is advantageous for one infection, may result in adverse outcomes for another. It is important to understand host responses to TB vaccines, especially in areas where both TB and HIV/AIDS remain endemic.