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Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection.

Publication ,  Journal Article
Fouts, TR; Bagley, K; Prado, IJ; Bobb, KL; Schwartz, JA; Xu, R; Zagursky, RJ; Egan, MA; Eldridge, JH; LaBranche, CC; Montefiori, DC; Zagury, D ...
Published in: Proc Natl Acad Sci U S A
March 3, 2015

A guiding principle for HIV vaccine design has been that cellular and humoral immunity work together to provide the strongest degree of efficacy. However, three efficacy trials of Ad5-vectored HIV vaccines showed no protection. Transmission was increased in two of the trials, suggesting that this vaccine strategy elicited CD4+ T-cell responses that provide more targets for infection, attenuating protection or increasing transmission. The degree to which this problem extends to other HIV vaccine candidates is not known. Here, we show that a gp120-CD4 chimeric subunit protein vaccine (full-length single chain) elicits heterologous protection against simian-human immunodeficiency virus (SHIV) or simian immunodeficiency virus (SIV) acquisition in three independent rhesus macaque repeated low-dose rectal challenge studies with SHIV162P3 or SIVmac251. Protection against acquisition was observed with multiple formulations and challenges. In each study, protection correlated with antibody-dependent cellular cytotoxicity specific for CD4-induced epitopes, provided that the concurrent antivaccine T-cell responses were minimal. Protection was lost in instances when T-cell responses were high or when the requisite antibody titers had declined. Our studies suggest that balance between a protective antibody response and antigen-specific T-cell activation is the critical element to vaccine-mediated protection against HIV. Achieving and sustaining such a balance, while enhancing antibody durability, is the major challenge for HIV vaccine development, regardless of the immunogen or vaccine formulation.

Duke Scholars

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Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 3, 2015

Volume

112

Issue

9

Start / End Page

E992 / E999

Location

United States

Related Subject Headings

  • Recombinant Fusion Proteins
  • Male
  • Macaca mulatta
  • Immunity, Humoral
  • Immunity, Cellular
  • Humans
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Female
 

Citation

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Fouts, T. R., Bagley, K., Prado, I. J., Bobb, K. L., Schwartz, J. A., Xu, R., … Gallo, R. C. (2015). Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection. Proc Natl Acad Sci U S A, 112(9), E992–E999. https://doi.org/10.1073/pnas.1423669112
Fouts, Timothy R., Kenneth Bagley, Ilia J. Prado, Kathryn L. Bobb, Jennifer A. Schwartz, Rong Xu, Robert J. Zagursky, et al. “Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection.Proc Natl Acad Sci U S A 112, no. 9 (March 3, 2015): E992–99. https://doi.org/10.1073/pnas.1423669112.
Fouts TR, Bagley K, Prado IJ, Bobb KL, Schwartz JA, Xu R, et al. Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection. Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E992–9.
Fouts, Timothy R., et al. “Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection.Proc Natl Acad Sci U S A, vol. 112, no. 9, Mar. 2015, pp. E992–99. Pubmed, doi:10.1073/pnas.1423669112.
Fouts TR, Bagley K, Prado IJ, Bobb KL, Schwartz JA, Xu R, Zagursky RJ, Egan MA, Eldridge JH, LaBranche CC, Montefiori DC, Le Buanec H, Zagury D, Pal R, Pavlakis GN, Felber BK, Franchini G, Gordon S, Vaccari M, Lewis GK, DeVico AL, Gallo RC. Balance of cellular and humoral immunity determines the level of protection by HIV vaccines in rhesus macaque models of HIV infection. Proc Natl Acad Sci U S A. 2015 Mar 3;112(9):E992–E999.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

EISSN

1091-6490

Publication Date

March 3, 2015

Volume

112

Issue

9

Start / End Page

E992 / E999

Location

United States

Related Subject Headings

  • Recombinant Fusion Proteins
  • Male
  • Macaca mulatta
  • Immunity, Humoral
  • Immunity, Cellular
  • Humans
  • HIV Infections
  • HIV Envelope Protein gp120
  • HIV Antibodies
  • Female