Immune Correlates of Disease Progression in Linked HIV-1 Infection—Tuen 2019
Genetic and immunologic investigations of epidemiologically-linked HIV transmission reveal how immune responses affect clinical outcomes. Immune correlates of protection have been found in HIV-1 vaccine trials and animal research, but their relevance in spontaneous infection is uncertain. Over 15 years, four HIV-1+ Cameroonians—three epidemiologically linked in a polygamous heterosexual relationship and one incidence-matched case—were studied for heterologous and cross-neutralizing antibody responses, antibody binding, IgA/IgG levels, antibody-dependent cellular cytotoxicity (ADCC) against cells expressing wild-type or CD4-bound Env, viral evolution, Env epitopes, and host factors like HLA-I alleles. In the absence of strongly protective HLA-I or CCR5-32 alleles, members of the transmission cluster had rapid advancement and long-term non-progression after viral infection with related strains. IgG antibody binding to natural Env and V1V2 antibody binding responses in viruses with residue K169 in V2 were related with slower development and higher CD4/CD8 ratios. ADCC against CD4-bound Env cells and low Env-specific IgA/IgG ratios improved clinical outcomes. For the first time, V1V2-directed antibody responses and ADCC against cells expressing open, CD4-exposed Env in the presence of low plasma IgA/IgG ratios can correlate with clinical outcome in natural infection. These factors are similar to the key correlates of protection revealed post-hoc in the RV144 vaccination trial and may alter clinical development once infected. Immune correlate analysis in natural infection may help create vaccines.
Tuen, M., Bimela, J. S., Banin, A. N., Ding, S., Harkins, G. W., Weiss, S., Itri, V., Durham, A. R., Porcella, S. F., Soni, S., Mayr, L., Meli, J., Torimiro, J. N., Tongo, M., Wang, X., Kong, X. P., Nádas, A., Kaufmann, D. E., Brumme, Z. L., Nanfack, A. J., … Duerr, R. (2019). Immune Correlates of Disease Progression in Linked HIV-1 Infection. Frontiers in immunology, 10, 1062. https://doi.org/10.3389/fimmu.2019.01062
