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Journal of Virology, August 2005, p. 10386-10396, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10386-10396.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Influence of Glycosylation on the Efficacy of an Env-Based Vaccine against Simian Immunodeficiency Virus SIVmac239 in a Macaque AIDS Model

Kazuyasu Mori,1,2,3* Chie Sugimoto,1,2,3 Shinji Ohgimoto,4 Emi E. Nakayama,5 Tatsuo Shioda,5 Shigeru Kusagawa,1 Yutaka Takebe,1 Munehide Kano,1 Tetsuro Matano,6 Takae Yuasa,7 Daisuke Kitaguchi,7 Masaaki Miyazawa,7 Yumiko Takahashi,8 Michio Yasunami,8 Akinori Kimura,8 Naoki Yamamoto,1 Yasuo Suzuki,3,9 and Yoshiyuki Nagai10

AIDS Research Center, National Institute of Infectious Diseases, Shinjuku-ku, Tokyo 162-8640,1 Tsukuba Primate Research Center, National Institute of Biomedical Innovation, Tsukuba, Ibaraki 305-0843,2 CREST, Japan Science and Technology Agency, Kawaguchi, Saitama 332-0012,3 Microbiology and Genomics, Department of Genome Sciences, Kobe University School of Medicine, Kobe, Hyogo 650-0017,4 Department of Viral Infections, Research Institute for Microbial Diseases, Osaka University, Suita, Osaka 565-0871,5 Department of Microbiology, Graduate School of Medicine, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033,6 Department of Immunology, Kinki University School of Medicine, Osaka-Sayama, Osaka 589-8511,7 Department of Molecular Pathogenesis, Division of Medical Science, Medical Research Institute, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo 101-0062,8 Department of Biochemistry, University of Shizuoka School of Pharmaceutical Sciences and COE Program in the 21st Century, Shizuoka, Shizuoka 422-8526,9 Toyama Institute of Health, Kosugi, Toyama 939-0363, Japan,10

Received 8 December 2004/ Accepted 2 May 2005

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 ({Delta}5G). In {Delta}5G-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 {Delta}5G 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 {Delta}5G 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 {Delta}5G 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.

* Corresponding author. Mailing address: Tsukuba Primate Research Center, National Institute of Biomedical Innovation, 1 Hachimandai, Tsukuba, Ibaraki 305-0843, Japan. Phone: 81-29-837-2121. Fax: 81-29-837-0218. E-mail: mori{at}nibio.go.jp.

Journal of Virology, August 2005, p. 10386-10396, Vol. 79, No. 16
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.16.10386-10396.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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