Influence of glycosylation on the efficacy of an Env-based vaccine against simian immunodeficiency virus SIVmac239 in a macaque AIDS model.
The envelope glycoprotein (Env) of human immunodeficiency viruses (HIVs) and simian immunodeficiency viruses (SIVs) is heavily glycosylated, and this feature has been speculated to be a reason for the insufficient immune control of these viruses by their hosts. In a macaque AIDS model, we demonstrated that quintuple deglycosylation in Env altered a pathogenic virus, SIVmac239, into a novel attenuated mutant virus (delta5G). In delta5G-infected animals, strong protective immunity against SIVmac239 was elicited. These HIV and SIV studies suggested that an understanding of the role of glycosylation is critical in defining not only the virological properties but also the immunogenicity of Env, suggesting that glycosylation in Env could be modified for the development of effective vaccines. To examine the effect of deglycosylation, we constructed prime-boost vaccines consisting of Env from SIVmac239 and delta5G and compared their immunogenicities and vaccine efficacies by challenge infection with SIVmac239. Vaccination-induced immune responses differed between the two vaccine groups. Both Env-specific cellular and humoral responses were higher in wild-type (wt)-Env-immunized animals than in delta5G Env-immunized animals. Following the challenge, viral loads in SIVmac239 Env (wt-Env)-immunized animals were significantly lower than in vector controls, with controlled viral replication in the chronic phase. Unexpectedly, viral loads in delta5G Env-immunized animals were indistinguishable from those in vector controls. This study demonstrated that the prime-boost Env vaccine was effective against homologous SIVmac239 challenge. Changes in glycosylation affected both cell-mediated and humoral immune responses and vaccine efficacy.
Mori
Kazuyasu
K
AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. mori@nibio.go.jp
Sugimoto
Chie
C
Ohgimoto
Shinji
S
Nakayama
Emi E
EE
Shioda
Tatsuo
T
Kusagawa
Shigeru
S
Takebe
Yutaka
Y
Kano
Munehide
M
Matano
Tetsuro
T
Yuasa
Takae
T
Kitaguchi
Daisuke
D
Miyazawa
Masaaki
M
Takahashi
Yumiko
Y
Yasunami
Michio
M
Kimura
Akinori
A
Yamamoto
Naoki
N
Suzuki
Yasuo
Y
Nagai
Yoshiyuki
Y
D000818:Animals; D000914:Antibodies, Viral / Q000097:blood; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D015686:Gene Products, env / Q000276:immunology*; D006031:Glycosylation; D007114:Immunization; D008253:Macaca mulatta; D012107:Research Design; D018449:SAIDS Vaccines / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D019562:Viral Load; D014779:Virus Replication
D000914:Antibodies, Viral; D015686:Gene Products, env; D018449:SAIDS Vaccines