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Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine.

Publication ,  Journal Article
Kannanganat, S; Nigam, P; Velu, V; Earl, PL; Lai, L; Chennareddi, L; Lawson, B; Wilson, RL; Montefiori, DC; Kozlowski, PA; Moss, B; Amara, RR ...
Published in: J Immunol
December 15, 2010

The influence of preexisting immunity to viral vectors is a major issue for the development of viral-vectored vaccines. In this study, we investigate the effect of preexisting vaccinia virus immunity on the immunogenicity and efficacy of a DNA/modified vaccinia Ankara (MVA) SIV vaccine in rhesus macaques using a pathogenic intrarectal SIV251 challenge. Preexisting immunity decreased SIV-specific CD8 and CD4 T cell responses but preserved the SIV-specific humoral immunity. In addition, preexisting immunity did not diminish the control of an SIV challenge mediated by the DNA/MVA vaccine. The peak and set point viremia was 150- and 17-fold lower, respectively, in preimmune animals compared with those of control animals. The peak and set point viremia correlated directly with colorectal virus at 2 wk postchallenge suggesting that early control of virus replication at the site of viral challenge was critical for viral control. Factors that correlated with early colorectal viral control included 1) the presence of anti-SIV IgA in rectal secretions, 2) high-avidity binding Ab for the native form of Env, and 3) low magnitude of vaccine-elicited SIV-specific CD4 T cells displaying the CCR5 viral coreceptor. The frequency of SIV-specific CD8 T cells in blood and colorectal tissue at 2 wk postchallenge did not correlate with early colorectal viral control. These results suggest that preexisting vaccinia virus immunity may not limit the potential of recombinant MVA vaccines to elicit humoral immunity and highlight the importance of immunodeficiency virus vaccines achieving early control at the mucosal sites of challenge.

Duke Scholars

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2010

Volume

185

Issue

12

Start / End Page

7262 / 7273

Location

United States

Related Subject Headings

  • Virus Replication
  • Viremia
  • Vaccinia virus
  • Vaccines, DNA
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Receptors, CCR5
  • Macaca mulatta
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Kannanganat, S., Nigam, P., Velu, V., Earl, P. L., Lai, L., Chennareddi, L., … Amara, R. R. (2010). Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine. J Immunol, 185(12), 7262–7273. https://doi.org/10.4049/jimmunol.1000751
Kannanganat, Sunil, Pragati Nigam, Vijayakumar Velu, Patricia L. Earl, Lilin Lai, Lakshmi Chennareddi, Benton Lawson, et al. “Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine.J Immunol 185, no. 12 (December 15, 2010): 7262–73. https://doi.org/10.4049/jimmunol.1000751.
Kannanganat S, Nigam P, Velu V, Earl PL, Lai L, Chennareddi L, et al. Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine. J Immunol. 2010 Dec 15;185(12):7262–73.
Kannanganat, Sunil, et al. “Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine.J Immunol, vol. 185, no. 12, Dec. 2010, pp. 7262–73. Pubmed, doi:10.4049/jimmunol.1000751.
Kannanganat S, Nigam P, Velu V, Earl PL, Lai L, Chennareddi L, Lawson B, Wilson RL, Montefiori DC, Kozlowski PA, Moss B, Robinson HL, Amara RR. Preexisting vaccinia virus immunity decreases SIV-specific cellular immunity but does not diminish humoral immunity and efficacy of a DNA/MVA vaccine. J Immunol. 2010 Dec 15;185(12):7262–7273.

Published In

J Immunol

DOI

EISSN

1550-6606

Publication Date

December 15, 2010

Volume

185

Issue

12

Start / End Page

7262 / 7273

Location

United States

Related Subject Headings

  • Virus Replication
  • Viremia
  • Vaccinia virus
  • Vaccines, DNA
  • Simian immunodeficiency virus
  • Simian Immunodeficiency Virus
  • Simian Acquired Immunodeficiency Syndrome
  • SAIDS Vaccines
  • Receptors, CCR5
  • Macaca mulatta