| Literature DB >> 23820294 |
Viraj Kulkarni1, Margherita Rosati2, Antonio Valentin2, Rashmi Jalah1, Candido Alicea1, Lei Yu3, Yongjun Guan3, Xiaoying Shen4, Georgia D Tomaras4, Celia LaBranche4, David C Montefiori4, Carmela Irene5, Rajasekhar Prattipati5, Abraham Pinter5, Sean M Sullivan6, George N Pavlakis2, Barbara K Felber1.
Abstract
We evaluated the immunogenicity and efficacy of Vaxfectin(®) adjuvanted SIV DNA vaccines in mice and macaques. Vaccination of mice with Vaxfectin(®) adjuvanted SIV gag DNA induced higher humoral immune responses than administration of unadjuvanted DNA, whereas similar levels of cellular immunity were elicited. Vaxfectin(®) adjuvanted SIVmac251 gag and env DNA immunization of rhesus macaques was used to examine magnitude, durability, and efficacy of humoral immunity. Vaccinated macaques elicited potent neutralizing antibodies able to cross-neutralize the heterologous SIVsmE660 Env. We found remarkable durability of Gag and Env humoral responses, sustained during ~2 y of follow-up. The Env-specific antibody responses induced by Vaxfectin(®) adjuvanted env DNA vaccination disseminated into mucosal tissues, as demonstrated by their presence in saliva, including responses to the V1-V2 region, and rectal fluids. The efficacy of the immune responses was evaluated upon intrarectal challenge with low repeated dose SIVmac251. Although 2 of the 3 vaccinees became infected, these animals showed significantly lower peak virus loads and lower chronic viremia than non-immunized infected controls. Thus, Vaxfectin(®) adjuvanted DNA is a promising vaccine approach for inducing potent immune responses able to control the highly pathogenic SIVmac251.Entities:
Keywords: HIV; Rhesus macaques; SIVmac239; SIVsmE660; V1 and V2 antibodies; adjuvant; antibody; avidity; mucosal immunity; neutralizing antibody; rectal fluid; saliva; systemic immunity
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Year: 2013 PMID: 23820294 PMCID: PMC3906391 DOI: 10.4161/hv.25442
Source DB: PubMed Journal: Hum Vaccin Immunother ISSN: 2164-5515 Impact factor: 3.452