Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques

L Jean Patterson; Jennifer Beal; Thorsten Demberg; Ruth H Florese; Nina Malkevich; David Venzon; Kris Aldrich; Ersell Richardson; V S Kalyanaraman; Irene Kalisz; Eun Mi Lee; David C Montefiori; Frank A Robey; Marjorie Robert-Guroff

doi:10.1016/j.virol.2007.12.037

Replicating adenovirus HIV/SIV recombinant priming alone or in combination with a gp140 protein boost results in significant control of viremia following a SHIV89.6P challenge in Mamu-A*01 negative rhesus macaques

Virology. 2008 May 10;374(2):322-37. doi: 10.1016/j.virol.2007.12.037. Epub 2008 Feb 5.

Authors

L Jean Patterson¹, Jennifer Beal, Thorsten Demberg, Ruth H Florese, Nina Malkevich, David Venzon, Kris Aldrich, Ersell Richardson, V S Kalyanaraman, Irene Kalisz, Eun Mi Lee, David C Montefiori, Frank A Robey, Marjorie Robert-Guroff

Affiliation

¹ Vaccine Branch, National Cancer Institute, Bethesda, MD 20892, USA.

PMID: 18252262
DOI: 10.1016/j.virol.2007.12.037

Abstract

Previously, replicating adenovirus type 5 host range (Ad5hr)-HIV/SIV recombinant priming in combination with SIV envelope boosting, resulted in significant, durable protection in 39% of rhesus macaques after SIVmac251 challenge. Both Env-specific antibody mediating ADCC, and cellular immunity correlated with protection. Here we evaluate the relative immunogenicities of novel HIV proteins and their contribution to protection in a SHIV89.6P model. All groups were primed with Ad-HIVenv89.6P, SIVgag239, and SIVnef239 recombinants. One group was not boosted, one received HIV89.6Pgp140DeltaCFI protein, and one a novel HIV-1 poly-peptide "peptomer". The HIV89.6Pgp140DeltaCFI protein in adjuvant strongly boosted Env-specific antibody and memory T cell responses in blood and tissue, resulting in significant reductions in acute and set point viremia. Macaques not boosted, showed a significant reduction in set point viremia, a full 32 weeks after the last Ad priming immunization. The HIV peptomer-boosted group showed a trend toward chronic viremia reduction, but was not protected.

Publication types

Research Support, N.I.H., Extramural

MeSH terms

AIDS Vaccines / administration & dosage
AIDS Vaccines / immunology
Adenoviridae / genetics
Adenoviridae / physiology*
Animals
Genetic Vectors*
HIV Antibodies / blood
HIV Infections / prevention & control
HIV-1 / genetics
HIV-1 / immunology*
HIV-1 / pathogenicity
Histocompatibility Antigens Class I / metabolism
Humans
Immunization
Immunization, Secondary
Macaca mulatta
Male
Recombination, Genetic
SAIDS Vaccines / administration & dosage
SAIDS Vaccines / immunology
Simian Acquired Immunodeficiency Syndrome / prevention & control
Simian Immunodeficiency Virus / genetics
Simian Immunodeficiency Virus / immunology*
Simian Immunodeficiency Virus / pathogenicity
Simian Immunodeficiency Virus / radiation effects
T-Lymphocytes / immunology
Viremia / prevention & control*
Virus Replication
env Gene Products, Human Immunodeficiency Virus / administration & dosage
env Gene Products, Human Immunodeficiency Virus / immunology*

Substances

AIDS Vaccines
HIV Antibodies
Histocompatibility Antigens Class I
Mamu-A 01 antigen
SAIDS Vaccines
env Gene Products, Human Immunodeficiency Virus
gp140 envelope protein, Human immunodeficiency virus 1

Grants and funding

AI 30034/AI/NIAID NIH HHS/United States