Seaton Kelly E, Deal Aaron, Han Xue, Li Shuying S, Clayton Ashley, Heptinstall Jack, Duerr Ann, Allen Mary A, Shen Xiaoying, Sawant Sheetal, Yates Nicole L, Spearman Paul, Churchyard Gavin, Goepfert Paul A, Maenza Janine, Gray Glenda, Pantaleo Giuseppe, Polakowski Laura, Robinson Harriet L, Grant Shannon, Randhawa April K, Huang Ying, Morgan Cecilia, Grunenberg Nicole, Karuna Shelly, Gilbert Peter B, McElrath M Juliana, Huang Yunda, Tomaras Georgia D
Duke Human Vaccine Institute, Durham, NC, USA.
Department of Surgery, Duke University, Durham, NC, USA.
NPJ Vaccines. 2021 Apr 15;6(1):56. doi: 10.1038/s41541-021-00305-8.
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.
我们在六项研究不同含包膜(Env)免疫原的HIV-1疫苗试验中研究了黏膜免疫反应。方案分为四类:DNA/载体、DNA/载体加蛋白质、单独蛋白质和单独载体。我们测量了来自宫颈拭子(n = 111)、直肠拭子(n = 154)、唾液(n = 141)和精液(n = 124)分泌物中的HIV-1特异性IgG和IgA,并与相应的血液水平进行比较。含蛋白质的方案有高达100%的应答率和最高的Env特异性IgG应答率。DNA/载体组引发的黏膜Env特异性IgG应答率高达67%,且因标本类型而异。几乎未观察到黏膜IgA应答。总体而言,gp41和gp140特异性抗体在gp120黏膜应答中占主导。在一项试验中,先前接种含蛋白质免疫原可使宫颈和直肠IgG的持久性维持长达17年。再次接种后黏膜IgG应答增强。这些发现突出了蛋白质免疫在引发HIV-1特异性黏膜抗体中的作用以及HIV-1疫苗引发持久的HIV-1特异性黏膜IgG的能力。