CD8 T Cells Show Protection against Highly Pathogenic Simian Immunodeficiency Virus (SIV) after Vaccination with SIV Gene-Expressing BCG Prime and Vaccinia Virus/Sendai Virus Vector Boosts

Author:

Kato Seiichi12,Shida Hisatoshi34,Okamura Tomotaka1,Zhang Xianfeng3,Miura Tomoyuki4,Mukai Tetsu5,Inoue Makoto6,Shu Tsugumine6,Naruse Taeko K.78,Kimura Akinori7,Yasutomi Yasuhiro1,Matsuo Kazuhiro2ORCID

Affiliation:

1. Tsukuba Primate Research Center, National Institutes of Biomedical Innovation, Health and Nutrition, Ibaraki, Japan

2. Research & Development Department, Japan BCG Laboratory, Tokyo, Japan

3. Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan

4. Institute for Frontier Life and Medical Sciences, Kyoto University, Kyoto, Japan

5. Leprosy Research Center, National Institute of Infectious Diseases, Tokyo, Japan

6. ID Pharma Co., Ltd., Ibaraki, Japan

7. Tokyo Medical and Dental University, Tokyo, Japan

8. Department of Immunogenetics, Institute of Tropical Medicine, Nagasaki University, Nagasaki, Japan

Abstract

Because both AIDS and tuberculosis are serious health threats in middle/low-income countries, development of a dual vaccine against them would be highly beneficial. To approach the goal, here we first assessed a urease-deficient bacillus Calmette-Guérin (BCG) for improvement of immunogenicity against both Mycobacterium tuberculosis and SIV. Second, we demonstrated the usefulness of Asian-origin cynomolgus monkeys for development of a preclinical AIDS vaccine by direct comparison with Indian rhesus macaques as the only validated hosts that identically mirror the outcomes of clinical trials, since the availability of Indian rhesus macaques is limited in countries other than the United States. Finally, we report the protective effect of a vaccination regimen comprising BCG, the highly attenuated vaccinia virus LC16m8Δ strain, and nontransmissible Sendai virus as safe vectors expressing SIV genes using repeated mucosal challenge with highly pathogenic SIVmac251. Identification of CD8 + T cells as a protective immunity suggests a future direction of AIDS vaccine development.

Funder

MEXT | Japan Society for the Promotion of Science

MEXT | Japan Science and Technology Agency

Japan Health Foundation

Publisher

American Society for Microbiology

Subject

Virology,Insect Science,Immunology,Microbiology

Reference55 articles.

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