Vaccination with Vaxfectin® adjuvanted SIV DNA induces long-lasting humoral immune responses able to reduce SIVmac251 Viremia

Viraj Kulkarni, Margherita Rosati, Antonio Valentin, Rashmi Jalah, Candido Alicea, Lei Yu, Yongjun Guan, Xiaoying Shen, Georgia D. Tomaras, Celia La Branche, David C. Montefiori, Carmela Irene, Rajasekhar Prattipati, Abraham Pinter, Sean M. Sullivan, George N. Pavlakis, Barbara K. Felber

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2069-2080
Number of pages12
JournalHuman Vaccines and Immunotherapeutics
Volume9
Issue number10
DOIs
StatePublished - Oct 2013
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology
  • Pharmacology

Keywords

  • Adjuvant
  • Antibody
  • Avidity
  • HIV
  • Mucosal immunity
  • Rectal fluid
  • Rhesus macaques
  • SIVmac239; neutralizing antibody
  • SIVsmE660
  • Saliva
  • Systemic immunity
  • V1 and V2 antibodies

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