Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform

Elizabeth S. Gabitzsch, Joseph P. Balint-Junior, Younong Xu, Stephanie Balcaitis, Brigitte Sanders-Beer, Julie Karl, Kent J. Weinhold, Slobodan Paessler, Frank R. Jones

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Anti-vector immunity mitigates immune responses induced by recombinant adenovirus vector vaccines, limiting their prime-boost capabilities. We have developed a novel gene delivery and expression platform (Ad5 [E1-, E2b-]) that induces immune responses despite pre-existing and/or developed concomitant Ad5 immunity. In the present study, we evaluated if this new Ad5 platform could overcome the adverse condition of pre-existing Ad5 immunity to induce effective immune responses in prime-boost immunization regimens against two different infectious diseases in the same animal. Ad5 immune rhesus macaques (RM) were immunized multiple times with the Ad5 [E1-, E2b-] platform expressing antigens from simian immunodeficiency virus (SIV). Immunized RM developed cell-mediated immunity against SIV antigens Gag, Pol, Nef and Env as well as antibody against Env. Vaccinated and vector control RMs were challenged intra-rectally with homologous SIVmac239. During a 7-week follow-up, there was perturbation of SIV load in some immunized RM. At 7 weeks post-challenge, eight immunized animals (53%) did not have detectable SIV, compared to two RM controls (13%) (P< 0.02; log-rank Mantel-Cox test). There was no correlation of protective MHC contributing to infection control. The RM without detectable circulating SIV, now hyper immune to Ad5, were then vaccinated with the same Ad5 [E1-, E2b-] platform expressing H1N1 influenza hemagglutinin (HA). Thirty days post Ad5 [E1-, E2b-]-HA vaccination, significant levels of influenza neutralizing antibody were induced in all animals that increased after an Ad5 [E1-, E2b-]-HA homologous boost. These data demonstrate the versatility of this new vector platform to immunize against two separate disease targets in the same animal despite the presence of immunity against the delivery platform, permitting homologous repeat immunizations with an Ad5 gene delivery platform.

Original languageEnglish (US)
Pages (from-to)7265-7270
Number of pages6
JournalVaccine
Volume30
Issue number50
DOIs
StatePublished - Nov 26 2012

Fingerprint

Simian immunodeficiency virus
Simian Immunodeficiency Virus
Pandemics
pandemic
Virus Diseases
Macaca mulatta
Immunity
immunity
Hemagglutinins
hemagglutinins
infection
immune response
gene transfer
influenza
Human Influenza
Immunization
animals
immunization
Adenovirus Vaccines
env Gene Products

Keywords

  • Ad5 [E1-, E2b-]
  • Ad5 immunity
  • Adenovirus vector
  • HIV vaccine
  • SIVmac239

ASJC Scopus subject areas

  • Immunology and Microbiology(all)
  • Infectious Diseases
  • Public Health, Environmental and Occupational Health
  • veterinary(all)
  • Molecular Medicine

Cite this

Gabitzsch, E. S., Balint-Junior, J. P., Xu, Y., Balcaitis, S., Sanders-Beer, B., Karl, J., ... Jones, F. R. (2012). Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform. Vaccine, 30(50), 7265-7270. https://doi.org/10.1016/j.vaccine.2012.09.058

Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform. / Gabitzsch, Elizabeth S.; Balint-Junior, Joseph P.; Xu, Younong; Balcaitis, Stephanie; Sanders-Beer, Brigitte; Karl, Julie; Weinhold, Kent J.; Paessler, Slobodan; Jones, Frank R.

In: Vaccine, Vol. 30, No. 50, 26.11.2012, p. 7265-7270.

Research output: Contribution to journalArticle

Gabitzsch, ES, Balint-Junior, JP, Xu, Y, Balcaitis, S, Sanders-Beer, B, Karl, J, Weinhold, KJ, Paessler, S & Jones, FR 2012, 'Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform', Vaccine, vol. 30, no. 50, pp. 7265-7270. https://doi.org/10.1016/j.vaccine.2012.09.058
Gabitzsch, Elizabeth S. ; Balint-Junior, Joseph P. ; Xu, Younong ; Balcaitis, Stephanie ; Sanders-Beer, Brigitte ; Karl, Julie ; Weinhold, Kent J. ; Paessler, Slobodan ; Jones, Frank R. / Control of SIV infection and subsequent induction of pandemic H1N1 immunity in rhesus macaques using an Ad5 [E1-, E2b-] vector platform. In: Vaccine. 2012 ; Vol. 30, No. 50. pp. 7265-7270.
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