Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans
Kelly E. Seaton, Aaron Deal, Xue Han, Shuying S. Li, Ashley Clayton, Jack Heptinstall, Ann Duerr, Mary Allen, Xiaoying Shen, Sheetal Sawant, Nicole L. Yates, Paul Spearman, Gavin Churchyard, Paul Goepfert, Janine Maenza, Glenda Gray, Giuseppe Pantaleo, Laura Polakowski, Harriet L. Robinson, Shannon Grant, April K. Randhawa, Ying Huang, Cecilia Morgan, Nicole Grunenberg, Shelly Karuna, Peter B. Gilbert, M. Juliana McElrath, Yunda Huang, Georgia D. Tomaras, NIAID HIV Vaccine Trials Network (HVTN) 076, 088, 086, 096, 097, 205 Study Teams
Abstract
We studied mucosal immune responses in six HIV-1 vaccine trials investigating different envelope (Env)-containing immunogens. Regimens were classified into four categories: DNA/vector, DNA/vector plus protein, protein alone, and vector alone. We measured HIV-1-specific IgG and IgA in secretions from cervical (n = 111) and rectal swabs (n = 154), saliva (n = 141), and seminal plasma (n = 124) and compared to corresponding blood levels. Protein-containing regimens had up to 100% response rates and the highest Env-specific IgG response rates. DNA/vector groups elicited mucosal Env-specific IgG response rates of up to 67% that varied across specimen types. Little to no mucosal IgA responses were observed. Overall, gp41- and gp140-specific antibodies dominated gp120 mucosal responses. In one trial, prior vaccination with a protein-containing immunogen maintained durability of cervical and rectal IgG for up to 17 years. Mucosal IgG responses were boosted after revaccination. These findings highlight a role for protein immunization in eliciting HIV-1-specific mucosal antibodies and the ability of HIV-1 vaccines to elicit durable HIV-1-specific mucosal IgG.