Induction of HIV-specific antibody response and protection against vaginal SHIV transmission by intranasal immunization with inactivated SHIV-capturing nanospheres in macaques.
We have previously reported that concanavalin A-immobilized polystyrene nanospheres (Con A-NS) could efficiently capture HIV-1 particles and that intranasal immunization with inactivated HIV-1-capturing nanospheres (HIV-NS) induced vaginal anti-HIV-1 IgA antibody response in mice. In this study, to evaluate the protective effect of immunization, each three macaques was intranasally immunized with Con A-NS or inactivated simian/human immunodeficiency virus KU-2-capturing nanospheres (SHIV-NS) and then intravaginally challenged with a pathogenic virus, SHIV KU-2. After a series of six immunizations, vaginal anti-HIV-1 gp120 IgA and IgG antibodies were detected in all SHIV-NS-immunized macaques. After intravaginal challenge, one of the three macaques in each of the Con A-NS- and SHIV-NS-immunized groups was infected. Plasma viral RNA load of infected macaque in SHIV-NS-immunized macaques was substantially less than that in unimmunized control macaque and reached below the detectable level. However, it could not be determined whether intranasal immunization with SHIV-NS is effective in giving complete protection against intravaginal challenge. To explore the effect of the SHIV-NS vaccine, the remaining non-infected macaques were rechallenged intravenously with SHIV KU-2. After intravenous challenge, all macaques became infected. However, SHIV-NS-immunized macaques had lower viral RNA loads and higher CD4(+) T cell counts than unimmunized control macaques. Plasma anti-HIV-1 gp120 IgA and IgG antibodies were induced more rapidly in the SHIV-NS-immunized macaques than in the controls. The rapid antibody responses having neutralizing activity might contribute to the clearance of the challenge virus. Thus, SHIV-NS-immunized macaques exhibited partial protection to vaginal and systemic challenges with SHIV KU-2.
Miyake
Ariko
A
Laboratory of Primate Model, Experimental Research Center for Infectious Disease, Institute for Virus Research, Kyoto University, Kyoto, Japan.
Akagi
Takami
T
Enose
Yoshimi
Y
Ueno
Masamichi
M
Kawamura
Masaki
M
Horiuchi
Reii
R
Hiraishi
Katsuya
K
Adachi
Masakazu
M
Serizawa
Takeshi
T
Narayan
Opendra
O
Akashi
Mitsuru
M
Baba
Masanori
M
Hayami
Masanori
M
D016915:AIDS Vaccines / Q000276:immunology*; D000281:Administration, Intranasal; D000818:Animals; D003208:Concanavalin A; D005260:Female; D041981:Gastrointestinal Tract / Q000276:immunology; D015483:HIV Antibodies / Q000097:blood* / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015658:HIV Infections / Q000517:prevention & control / Q000635:transmission*; D018928:Immunity, Mucosal; D007136:Immunoglobulins; D008253:Macaca mulatta; D043942:Nanotubes; D010949:Plasma / Q000276:immunology; D011137:Polystyrenes; D012367:RNA, Viral / Q000097:blood; D018449:SAIDS Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016097:Simian Acquired Immunodeficiency Syndrome / Q000517:prevention & control / Q000635:transmission*; D015302:Simian Immunodeficiency Virus / Q000276:immunology* / Q000472:pathogenicity; D014611:Vaccination; D015164:Vaccines, Inactivated; D014621:Vagina / Q000276:immunology; D019562:Viral Load
D016915:AIDS Vaccines; D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D011137:Polystyrenes; D012367:RNA, Viral; D018449:SAIDS Vaccines; D015164:Vaccines, Inactivated; D003208:Concanavalin A