Intranasal HIV-1-gp160-DNA/gp41 peptide prime-boost immunization regimen in mice results in long-term HIV-1 neutralizing humoral mucosal and systemic immunity.
An intranasal DNA vaccine prime followed by a gp41 peptide booster immunization was compared with gp41 peptide and control immunizations. Serum HIV-1-specific IgG and IgA as well as IgA in feces and vaginal and lung secretions were detected after immunizations. Long-term humoral immunity was studied for up to 12 mo after the booster immunization by testing the presence of HIV-1 gp41- and CCR5-specific Abs and IgG/IgA-secreting B lymphocytes in spleen and regional lymph nodes in immunized mice. A long-term IgA-specific response in the intestines, vagina, and lungs was obtained in addition to a systemic immune response. Mice immunized only with gp41 peptides and L3 adjuvant developed a long-term gp41-specific serum IgG response systemically, although over a shorter period (1-9 mo), and long-term mucosal gp41-specific IgA immunity. HIV-1-neutralizing serum Abs were induced that were still present 12 mo after booster immunization. HIV-1 SF2-neutralizing fecal and lung IgA was detectable only in the DNA-primed mouse groups. Intranasal DNA prime followed by one peptide/L3 adjuvant booster immunization, but not a peptide prime followed by a DNA booster, was able to induce B cell memory and HIV-1-neutralizing Abs for at least half of a mouse's life span.
Devito
Claudia
C
Swedish Institute for Infectious Disease Control and Microbiology and Tumorbiology Center, Department of Virology, Karolinska Institute, Solna, Sweden.
Zuber
Bartek
B
Schröder
Ulf
U
Benthin
Reinhold
R
Okuda
Kenji
K
Broliden
Kristina
K
Wahren
Britta
B
Hinkula
Jorma
J
D016915:AIDS Vaccines / Q000008:administration & dosage* / Q000276:immunology; D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology / Q000821:virology; D005243:Feces / Q000821:virology; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis*; D019302:HIV Envelope Protein gp160 / Q000008:administration & dosage* / Q000276:immunology; D015700:HIV Envelope Protein gp41 / Q000008:administration & dosage* / Q000276:immunology; D015497:HIV-1 / Q000276:immunology*; D007110:Immunity, Active; D018928:Immunity, Mucosal; D007117:Immunization, Secondary / Q000379:methods; D007070:Immunoglobulin A / Q000096:biosynthesis; D007074:Immunoglobulin G / Q000096:biosynthesis; D007156:Immunologic Memory; D007421:Intestine, Small / Q000276:immunology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009297:Nasal Mucosa / Q000276:immunology* / Q000821:virology; D009500:Neutralization Tests; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology; D019444:Vaccines, DNA / Q000008:administration & dosage* / Q000276:immunology; D022223:Vaccines, Subunit / Q000008:administration & dosage* / Q000276:immunology; D014621:Vagina / Q000276:immunology / Q000378:metabolism / Q000821:virology
D016915:AIDS Vaccines; D015483:HIV Antibodies; D019302:HIV Envelope Protein gp160; D015700:HIV Envelope Protein gp41; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D019444:Vaccines, DNA; D022223:Vaccines, Subunit