Vaccination with gp120-depleted HIV-1 plus immunostimulatory CpG oligodeoxynucleotides in incomplete Freund's adjuvant stimulates cellular and humoral immunity in rhesus macaques

• Published in: Vaccine Vol. 23; no. 6; pp. 827 - 839
• Main Authors: Silvera, Peter, Savary, Jay R., Livingston, Virginia, White, Jessica, Manson, Kelledy H., Wyand, Michael H., Salk, Peter L., Moss, Ronald B., Lewis, Mark G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 21.12.2004; Elsevier; Elsevier Limited
• Subjects: AIDS Vaccines - administration & dosage; AIDS Vaccines - immunology; Amino acids; Animals; Antibody Formation; Antiretroviral drugs; Applied microbiology; Biological and medical sciences; CpG Islands - immunology; CpG ODN; Freund's Adjuvant - immunology; Fundamental and applied biological sciences. Psychology; HIV; HIV Antibodies - biosynthesis; HIV Envelope Protein gp120 - genetics; HIV Infections - immunology; HIV Infections - prevention & control; HIV-1 - genetics; HIV-1 - immunology; HIV-1 vaccine; Human immunodeficiency virus; Human immunodeficiency virus 1; Immune system; Immunity, Cellular; Immunization; Immunogenicity; Interferon-gamma - immunology; Laboratory animals; Lymphocytes; Macaca mulatta; Microbiology; Miscellaneous; Peptides; Studies; Vaccination; Vaccines; Vaccines, antisera, therapeutical immunoglobulins and monoclonal antibodies (general aspects); Viral infections; Virology; Immunogenicity; HIV-1 vaccine; CpG ODN; Drug combination; HIV-1 virus; Vaccination; Retroviridae; Cellular immunity; Macaca mulatta; Vaccine; Lentivirus; Virus; Vertebrata; Mammalia; Immunological adjuvant; Primates; Simioidea; Human immunodeficiency virus; Humoral immunity
• ISSN: 0264-410X; 1873-2518
• DOI: 10.1016/j.vaccine.2004.06.045

Whole killed human immunodeficiency virus type 1 (HIV-1) immunogens contain the more conserved epitopes of HIV-1 and therefore may provide some utility as potential HIV-1 vaccine candidates. Previous studies have shown that synthetic oligodeoxynucleotides (ODN) containing unmethylated cytosine–guanine (CpG) dinucleotides trigger rapid stimulation of both CD4+ and CD8+ T cells. Here, we investigated whether immunization of rhesus macaques with an inactivated gp120-depleted HIV-1 immunogen, emulsified in incomplete Freund's adjuvant (IFA) together with immunostimulatory CpG-containing ODN (ODN 2006), would elicit HIV-specific cellular and humoral immune responses. High titer anti-p24 antibody levels were induced in all four immunized animals that were sustained 6 weeks after the fifth and final boost at 23 months. These anti-gag antibodies mapped to linear B-cell epitopes within the matrix (MA), capsid (CA), p2, nucleocapsid (NC) and p6 proteins of HIV-1 gag. HIV-specific interferon-γ-producing CD4+ and CD8+ T-cell responses were measured before and after the fourth and fifth immunizations by both intracellular cytokine (ICC) and ELISPOT techniques; responses were detected in three of the four immunized animals. CD4+ T-cell epitopes appear to map within amino acids 261–290 and 291–320 of p24 CA protein. Immunizations were well tolerated both locally and systemically. Based on these results, further studies of this approach are warranted.