HIV-1 Env DNA vaccine plus protein boost delivered by EP expands B- and T-cell responses and neutralizing phenotype in vivo

• Published in: PloS one Vol. 8; no. 12; p. e84234
• Main Authors: Muthumani, Kar, Wise, Megan C, Broderick, Kate E, Hutnick, Natalie, Goodman, Jonathan, Flingai, Seleeke, Yan, Jian, Bian, Chaoran B, Mendoza, Janess, Tingey, Colleen, Wilson, Christine, Wojtak, Krzysztof, Sardesai, Niranjan Y, Weiner, David B
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.12.2013; Public Library of Science (PLoS)
• Subjects: Acquired immune deficiency syndrome; AIDS; AIDS vaccines; AIDS Vaccines - immunology; AIDS Vaccines - pharmacology; Animals; Antibodies; Antibodies, Neutralizing - immunology; B cells; Binding; Biocompatibility; Biology; Cell Line; Collaboration; Cytokines; Cytotoxicity; Deoxyribonucleic acid; DNA; DNA vaccines; Drug delivery systems; Electroporation; env Gene Products, Human Immunodeficiency Virus - genetics; env Gene Products, Human Immunodeficiency Virus - immunology; Enzyme-Linked Immunosorbent Assay; Enzyme-Linked Immunospot Assay; Flow Cytometry; Gene sequencing; Genetic aspects; Glycoprotein gp120; Guinea Pigs; HIV; Human immunodeficiency virus; Humans; Immune response; Immune response (cell-mediated); Immunity, Cellular - immunology; Immunization; Immunogenicity; Immunoglobulins; Laboratory animals; Lymphocytes B; Lymphocytes T; Medicine; Mice; Mice, Inbred BALB C; Neutralization; Neutralization Tests; Neutralizing; Nucleotide sequence; Pathology; Pharmaceuticals; Plasmids; Protein binding; Proteins; Recombinant Proteins - pharmacology; T cells; Toxicity; Vaccines; Viral envelope proteins; Virology; Viruses; United States > US
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0084234

An effective HIV vaccine will most likely require the induction of strong T-cell responses, broadly neutralizing antibodies (bNAbs), and the elicitation of antibody-dependent cellular cytotoxicity (ADCC). Previously, we demonstrated the induction of strong HIV/SIV cellular immune responses in macaques and humans using synthetic consensus DNA immunogens delivered via adaptive electroporation (EP). However, the ability of this improved DNA approach to prime for relevant antibody responses has not been previously studied. Here, we investigate the immunogenicity of consensus DNA constructs encoding gp140 sequences from HIV-1 subtypes A, B, C and D in a DNA prime-protein boost vaccine regimen. Mice and guinea pigs were primed with single- and multi-clade DNA via EP and boosted with recombinant gp120 protein. Sera were analyzed for gp120 binding and induction of neutralizing antibody activity. Immunization with recombinant Env protein alone induced low-titer binding antibodies with limited neutralization breath. In contrast, the synthetic DNA prime-protein boost protocol induced significantly higher antibody binding titers. Furthermore, sera from DNA prime-protein boost groups were able to neutralize a broader range of viruses in a panel of tier 1 clade B viruses as well as multiple tier 1 clade A and clade C viruses. Further investigation of synthetic DNA prime plus adaptive EP plus protein boost appears warranted.