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Hum Vaccin Immunother. 2013 Oct;9(10):2069-80. doi: 10.4161/hv.25442. Epub 2013 Jul 2.

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

Author information

1
Human Retrovirus Pathogenesis Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
2
Human Retrovirus Section; Vaccine Branch; Center for Cancer Research; National Cancer Institute; Frederick, MD USA.
3
Institute of Human Virology and Department of Microbiology & Immunology; University of Maryland School of Medicine; Baltimore, MD USA.
4
Duke Human Vaccine Institute; Durham, NC USA.
5
Public Health Research Institute; University of Medicine and Dentistry of New Jersey; Newark, NJ USA.
6
Vical Inc.; Pharmaceutical Sciences; San Diego, CA USA.

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.

KEYWORDS:

HIV; Rhesus macaques; SIVmac239; SIVsmE660; V1 and V2 antibodies; adjuvant; antibody; avidity; mucosal immunity; neutralizing antibody; rectal fluid; saliva; systemic immunity

PMID:
23820294
PMCID:
PMC3906391
DOI:
10.4161/hv.25442
[Indexed for MEDLINE]
Free PMC Article
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