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Systemic immunization with an ALVAC-HIV-1/protein boost vaccine strategy protects rhesus macaques from CD4(+) T-cell loss and reduces both systemic and mucosal simian-human immunodeficiency virus SHIVKU2 RNA levels

  1. Author:
    Pal, R.
    Venzon, D.
    Santra, S.
    Kalyanaraman, V. S.
    Montefiori, D. C.
    Hocker, L.
    Hudacik, L.
    Rose, N.
    Nacsa, J.
    Edghill-Smith, Y.
    Moniuszko, M.
    Hel, Z.
    Belyakov, I. M.
    Berzofsky, J. A.
    Parks, R. W.
    Markham, P. D.
    Letvin, N. L.
    Tartaglia, J.
    Franchini, G.

  2. Author Address

    NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, Bethesda, MD 20892 USA. Adv Biosci Labs Inc, Kensington, MD 20895 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Div Viral Pathogenesis, Beth Israel Deaconess Med Ctr,Dept Med, Boston, MA 02215 USA. Duke Univ, Med Ctr, Dept Surg, Ctr AIDS Res, Durham, NC 27710 USA. Med Univ Bialystok, Dept Allergol & Internal Dis, PL-15276 Bialystok, Poland. So Res Inst, Frederick, MD 21701 USA. Univ Alabama, Dept Pathol, Ctr AIDS Res, Birmingham, AL 35249 USA. NCI, Mol Immunogenet & Vaccine Res Sect, Vaccine Branch, Bethesda, MD 20892 USA. Sanofi Pasteur, Toronto, ON M2R 3T4, Canada.;Franchini, G, NCI, Anim Models & Retroviral Vaccines Sect, Vaccine Branch, 41-D804, Bethesda, MD 20892 USA.;franchig@mail.nih.gov
    1. Year: 2006
    2. Date: Apr
  2. Journal: Journal of Virology
    1. 80
    2. 8
    3. Pages: 3732-3742
  4. Type of Article: Article
  5. ISSN: 0022-538X
  1. Abstract:

    Transmission of human immunodeficiency virus type 1 (HIV-1) occurs primarily via the mucosal route, suggesting that HIV-1 vaccines may need to elicit mucosal immune responses. Here, we investigated the immunogenicity and relative efficacy of systemic immunization with two human ALVAC-HIV-1 recombinant vaccines expressing Gag, Pol, and gp120 (vCP250) or Gag, Pol, and gp160 (vCP1420) in a prime-boost protocol with their homologous vaccine native Env proteins. The relative efficacy was measured against a high-dose mucosal exposure to the pathogenic neutralization-resistant variant SHIVKU2 (simian-human immunodeficiency virus). Systemic immunization with both vaccine regimens decreased viral load levels not only in blood but unexpectedly also in mucosal sites and protected macaques from peripheral CD4(+) T-cell loss. This protective effect was stronger when the gp120 antigen was included in the vaccine. Inclusion of recombinant Tat protein in the boosting phase along with the Env protein did not contribute further to the preservation of CD4(+) T cells. Thus, systemic immunization with ALVAC-HIV-1 vaccine candidates elicits anti-HIV-1 immune responses able to contain virus replication also at mucosal sites in macaques.

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  2. DOI: 10.1128/jvi.80.8.3732-3742.2006
  3. View record in Web of Science®
  4. WOS: 000236685600005

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