Antibodies to gp120 and PD-1 expression on virus-specific CD8+ T cells in protection from simian AIDS.

Abstract

We compared the relative efficacies against simian immunodeficiency virus (SIV) challenge of three vaccine regimens that elicited similar frequencies of SIV-specific CD4(+) and CD8(+) T-cell responses but differed in the level of antibody responses to the gp120 envelope protein. All macaques were primed with DNA plasmids expressing SIV gag, pol, env, and Retanef genes and were boosted with recombinant modified vaccinia Ankara virus (MVA) expressing the same genes, either once (1 × MVA) or twice (2 × MVA), or were boosted once with MVA followed by a single boost with replication-competent adenovirus (Ad) type 5 host range mutant (Ad5 h) expressing SIV gag and nef genes but not Retanef or env (1 × MVA/Ad5). While two of the vaccine regimens (1 × MVA and 1 × MVA/Ad5) protected from high levels of SIV replication only during the acute phase of infection, the 2 × MVA regimen, with the highest anti-SIV gp120 titers, protected during the acute phase and transiently during the chronic phase of infection. Mamu-A*01 macaques of this third group exhibited persistent Gag CD8(+)CM9(+) effector memory T cells with low expression of surface Programmed death-1 (PD-1) receptor and high levels of expression of genes associated with major histocompatibility complex class I (MHC-I) and MHC-II antigen. The fact that control of SIV replication was associated with both high titers of antibodies to the SIV envelope protein and durable effector SIV-specific CD8(+) T cells suggests the hypothesis that the presence of antibodies at the time of challenge may increase innate immune recruiting activity by enhancing antigen uptake and may result in improvement of the quality and potency of secondary SIV-specific CD8(+) T-cell responses.

• Authors: Monica Vaccari, Rabih Halwani, L Jean Patterson, Adriano Boasso, Jennifer Beal, Elzbieta Tryniszewska, Anna Hryniewicz, David Venzon, Elias K Haddad, Mohamed El-Far, Margherita Rosati, George N Pavlakis, Barbara K Felber, Saleh Al-Muhsen, Marjorie Robert-Guroff, Rafick-Pierre Sekaly, Genoveffa Franchini
• Journal: Journal of virology (J Virol) Vol. 87 Issue 6 Pg. 3526-37 (Mar 2013) ISSN: 1098-5514 [Electronic] United States
• PMID: 23325679 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)

Chemical References

• Antibodies, Viral
• Membrane Glycoproteins
• Programmed Cell Death 1 Receptor
• SAIDS Vaccines
• Vaccines, DNA
• Vaccines, Synthetic
• Viral Envelope Proteins
• gp120 protein, Simian immunodeficiency virus

Topics

• Animals
• Antibodies, Viral (blood)
• CD8-Positive T-Lymphocytes (immunology)
• Immunologic Memory
• Macaca
• Membrane Glycoproteins (immunology)
• Programmed Cell Death 1 Receptor (immunology)
• SAIDS Vaccines (administration & dosage, immunology)
• Simian Acquired Immunodeficiency Syndrome (immunology, prevention & control)
• Simian Immunodeficiency Virus (immunology)
• Vaccination (methods)
• Vaccines, DNA (administration & dosage, immunology)
• Vaccines, Synthetic (administration & dosage, immunology)
• Viral Envelope Proteins (immunology)