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 language | English (US) |
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Pages (from-to) | 2069-2080 |
Number of pages | 12 |
Journal | Human Vaccines and Immunotherapeutics |
Volume | 9 |
Issue number | 10 |
DOIs | |
State | Published - Oct 2013 |
Externally published | Yes |
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