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Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge
Journal article   Open access   Peer reviewed

Chemokine-adjuvanted electroporated DNA vaccine induces substantial protection from simian immunodeficiency virus vaginal challenge

M A Kutzler, M C Wise, N A Hutnick, Z Moldoveanu, M Hunter, M Reuter, S Yuan, J Yan, A Ginsberg, A Sylvester, …
Mucosal immunology, v 9(1), pp 13-23
Jan 2016
PMID: 25943275
url
https://doi.org/10.1038/mi.2015.31View
Published, Version of Record (VoR) Open

Abstract

Receptors, CCR10 - genetics Vaccines, DNA - genetics Chemokines - administration & dosage Adjuvants, Immunologic - administration & dosage Vagina - drug effects Vaccination AIDS Vaccines - immunology Vaccines, DNA - immunology Vagina - immunology Macaca mulatta Vaccines, DNA - administration & dosage Immunity, Mucosal - drug effects Simian Acquired Immunodeficiency Syndrome - virology Immunity, Cellular - drug effects Female Chemokines - immunology Simian Immunodeficiency Virus - immunology Antibodies, Viral - biosynthesis Plasmids - immunology Receptors, CCR - genetics Chemokines - genetics Receptors, CCR10 - immunology Simian Acquired Immunodeficiency Syndrome - prevention & control Animals Receptors, CCR - immunology Simian Acquired Immunodeficiency Syndrome - immunology Plasmids - chemistry Vagina - virology AIDS Vaccines - genetics Ligands AIDS Vaccines - administration & dosage Simian Immunodeficiency Virus - drug effects
There have been encouraging results for the development of an effective HIV vaccine. However, many questions remain regarding the quality of immune responses and the role of mucosal antibodies. We addressed some of these issues by using a simian immunodeficiency virus (SIV) DNA vaccine adjuvanted with plasmid-expressed mucosal chemokines combined with an intravaginal SIV challenge in rhesus macaque (RhM) model. We previously reported on the ability of CCR9 and CCR10 ligand (L) adjuvants to enhance mucosal and systemic IgA and IgG responses in small animals. In this study, RhMs were intramuscularly immunized five times with either DNA or DNA plus chemokine adjuvant delivered by electroporation followed by challenge with SIVsmE660. Sixty-eight percent of all vaccinated animals (P<0.01) remained either uninfected or had aborted infection compared with only 14% in the vaccine naïve group. The highest protection was observed in the CCR10L chemokines group, where six of nine animals had aborted infection and two remained uninfected, leading to 89% protection (P<0.001). The induction of mucosal SIV-specific antibodies and neutralization titers correlated with trends in protection. These results indicate the need to further investigate the contribution of chemokine adjuvants to modulate immune responses and the role of mucosal antibodies in SIV/HIV protection.

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Web of Science research areas
Immunology
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