SIVmac239 MVA vaccine with and without a DNA prime, similar prevention of infection by a repeated dose SIVsmE660 challenge despite different immune responses

• Type of Material: Article
• Authors: Lilin Lai, Emory University; Sue-Fen Kwa, Emory University; Pamela A. Kozlowski, Louisiana State University; David C. Montefiori, Duke University Medical Center; Tracy Nolen, University of North Carolina; Michael G. Hudgens, University of North Carolina; Welkin E. Johnson, Harvard University; Guido Ferrari, Duke University; Vanessa M. Hirsch, National Institute of Allergy and Infectious Diseases; Barbara K. Felber, National Cancer Institute; George N. Pavlakis, National Cancer Institute; Patricia L. Earl, National Institute of Allergy and Infectious Diseases; Bernard Moss, National Institute of Allergy and Infectious Diseases; Rama Rao Amara, Emory University; Harriet Robinson, Emory University
• Language: English
• Date: 2012-02-21
• Publisher: Elsevier: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2011 Elsevier Ltd.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.vaccine.2011.12.026
• Title of Journal or Parent Work: Vaccine
• ISSN: 0264-410X
• Volume: 30
• Issue: 9
• Start Page: 1737
• End Page: 1745
• Keywords: DOMAIN; Medicine, Research & Experimental; RHESUS MACAQUES; DNA vaccine; Science & Technology; GP41 CYTOPLASMIC TAIL; MVA vaccine; Life Sciences & Biomedicine; MUCOSAL CHALLENGE; IMMUNODEFICIENCY VIRUS-VACCINE; HIV-1; ANTIBODY-RESPONSES; ENVELOPE PROTEIN; Simian immunodeficiency virus; Immunology; TRUNCATION; Avidity in protection; Vaccine; IMMUNOGENICITY; Immunodeficiency virus; Research & Experimental Medicine
• Research Categories: Biology, Virology; Health Sciences, Immunology

Abstract

Background: Vaccine regimens using different agents for priming and boosting have become popular for enhancing T cell and Ab responses elicited by candidate HIV/AIDS vaccines. Here we use a simian model to evaluate immunogenicity and protective efficacy of a recombinant modified vaccinia Ankara (MVA) vaccine in the presence and absence of a recombinant DNA prime. The simian vaccines and regimens represent prototypes for candidate HIV vaccines currently undergoing clinical testing. Method: Recombinant DNA and MVA immunogens expressed simian immunodeficiency virus (SIV)mac239 Gag, PR, RT, and Env sequences. Vaccine schedules tested inoculations of MVA at months 0, 2, and 6 (MMM regimen) or priming with DNA at months 0 and 2 and boosting with MVA at months 4 and 6 (DDMM regimen). Twelve weekly rectal challenges with the heterologous SIV smE660 were initiated at 6 months following the last immunization. Results: Both regimens elicited similar 61-64% reductions in the per challenge risk of SIVsmE660 transmission despite raising different patterns of immune responses. The DDMM regimen elicited higher magnitudes of CD4 T cells whereas the MMM regimen elicited higher titers and greater avidity Env-specific IgG and more frequent and higher titer SIV-specific IgA in rectal secretions. Both regimens elicited similar magnitudes of CD8 T cells. Magnitudes of T cell responses, specific activities of rectal IgA Ab, and the tested specificities for neutralization and antibody-dependent cellular cytotoxicity did not correlate with risk of infection. However, the avidity of Env-specific IgG had a strong correlation with the per challenge risk of acquisition, but only for the DDMM group. Conclusions: We conclude that for the tested immunogens in rhesus macaques, the simpler MMM regimen is as protective as the more complex DDMM regimen.