NPJ Vaccines. 2021 Apr 15; 6(1):56.

PubMed ID: 33859204

Meta-analysis of HIV-1 vaccine elicited mucosal antibodies in humans

Seaton KE, Deal A, Han X, Li SS, Clayton A, Heptinstall J, Duerr A, Allen MA, Shen X, Sawant S, Yates NL, Spearman P, Churchyard G, Goepfert PA, Maenza J, Gray G, Pantaleo G, Polakowski L, Robinson HL, Grant S, Randhawa AK, Huang Y, Morgan C, Grunenberg N, Karuna S, Gilbert PB, McElrath MJ, Huang Y, Tomaras GD, NIAID HIV Vaccine Trials Network (HVTN) 076, 088, 086, 096, 097, 205 Study Teams

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.