Immunogenicity and Efficacy of a Novel Multi-Antigenic Peptide Vaccine Based on Cross-Reactivity between Feline and Human Immunodeficiency Viruses
Bikash Sahay,
Alek M. Aranyos,
Meerambika Mishra,
Andrew C. McAvoy,
Marcus M. Martin,
Riuyu Pu,
Sayaka Shiomitsu,
Keijiro Shiomitsu,
Michael J. Dark,
Missa P. Sanou,
Shannon R. Roff,
Mobeen H. Rathore,
Janet K. Yamamoto
Affiliations
Bikash Sahay
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
Alek M. Aranyos
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
Meerambika Mishra
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
Andrew C. McAvoy
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
Sayaka Shiomitsu
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
Keijiro Shiomitsu
Department of Small Animal Clinical Sciences, College of Veterinary Medicine, University of Florida, P.O. Box 100116, Gainesville, FL 32610, USA
Michael J. Dark
Department of Comparative, Diagnostic & Population Medicine, College of Veterinary Medicine, University of Florida, P.O. Box 100123, Gainesville, FL 32610-0123, USA
Missa P. Sanou
Merck & Co., 770 Sumneytown Pike, North Wales, PA 19486, USA
Shannon R. Roff
Charles River Laboratories Inc., 15 Worman’s Mill Court, Suite I, Frederick, MD 21701, USA
Mobeen H. Rathore
Education, and Service (UF CARES), University of Florida Center for HIV/AIDS Research, Jacksonville, FL 32209-6810, USA
Janet K. Yamamoto
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, P.O. Box 110880, Gainesville, FL 32611-0880, USA
For the development of an effective HIV-1 vaccine, evolutionarily conserved epitopes between feline and human immunodeficiency viruses (FIV and HIV-1) were determined by analyzing overlapping peptides from retroviral genomes that induced both anti-FIV/HIV T cell-immunity in the peripheral blood mononuclear cells from the FIV-vaccinated cats and the HIV-infected humans. The conserved T-cell epitopes on p24 and reverse transcriptase were selected based on their robust FIV/HIV-specific CD8+ cytotoxic T lymphocyte (CTL), CD4+ CTL, and polyfunctional T-cell activities. Four such evolutionarily conserved epitopes were formulated into four multiple antigen peptides (MAPs), mixed with an adjuvant, to be tested as FIV vaccine in cats. The immunogenicity and protective efficacy were evaluated against a pathogenic FIV. More MAP/peptide-specific CD4+ than CD8+ T-cell responses were initially observed. By post-third vaccination, half of the MAP/peptide-specific CD8+ T-cell responses were higher or equivalent to those of CD4+ T-cell responses. Upon challenge, 15/19 (78.9%) vaccinated cats were protected, whereas 6/16 (37.5%) control cats remained uninfected, resulting in a protection rate of 66.3% preventable fraction (p = 0.0180). Thus, the selection method used to identify the protective FIV peptides should be useful in identifying protective HIV-1 peptides needed for a highly protective HIV-1 vaccine in humans.
