Prophylactic vaccination inducing anti-Env antibodies can result in protection against HTLV-1 challenge in macaques

• Published in: Molecular therapy Vol. 32; no. 7; pp. 2328 - 2339
• Main Authors: Nakamura-Hoshi, Midori, Ishii, Hiroshi, Nomura, Takushi, Nishizawa, Masako, Hau, Trang Thi Thu, Kuse, Nozomi, Okazaki, Midori, Ainai, Akira, Suzuki, Tadaki, Hasegawa, Hideki, Yoshida, Takeshi, Yonemitsu, Kenzo, Suzaki, Yuriko, Ami, Yasushi, Yamamoto, Hiroyuki, Matano, Tetsuro
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.07.2024
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; CD8-Positive T-Lymphocytes - immunology; cell-to-cell transmission; Disease Models, Animal; Gene Products, env - immunology; HTLV-1; HTLV-I Infections - immunology; HTLV-I Infections - prevention & control; Human T-lymphotropic virus 1 - immunology; Humans; Macaca fascicularis; macaque model; neutralizing antibody; Vaccination; vaccine; Viral Load; Viral Vaccines - administration & dosage; Viral Vaccines - immunology; neutralizing antibody; macaque model; vaccine; HTLV-1; cell-to-cell transmission
• ISSN: 1525-0016; 1525-0024; 1525-0024
• DOI: 10.1016/j.ymthe.2024.05.020

Human T cell leukemia/T-lymphotropic virus type 1 (HTLV-1) infection occurs by cell-to-cell transmission and can induce fatal adult T cell leukemia. Vaccine development is critical for the control of HTLV-1 transmission. However, determining whether vaccine-induced anti-Env antibodies can prevent cell-to-cell HTLV-1 transmission is challenging. Here, we examined the protective efficacy of a vaccine inducing anti-Env antibodies against HTLV-1 challenge in cynomolgus macaques. Eight of 10 vaccinated macaques produced anti-HTLV-1 neutralizing antibodies (NAbs) and were protected from an intravenous challenge with 108 HTLV-1-producing cells. In contrast, the 2 vaccinated macaques without NAb induction and 10 unvaccinated controls showed HTLV-1 infection with detectable proviral load after challenge. Five of the eight protected macaques were administered with an anti-CD8 monoclonal antibody, but proviruses remained undetectable and no increase in anti-HTLV-1 antibodies was observed even after CD8+ cell depletion in three of them. Analysis of Env-specific T cell responses did not suggest involvement of vaccine-induced Env-specific T cell responses in the protection. These results indicate that anti-Env antibody induction by vaccination can result in functionally sterile HTLV-1 protection, implying the rationale for strategies aimed at anti-Env antibody induction in prophylactic HTLV-1 vaccine development. [Display omitted] Matano and colleagues indicate that anti-Env antibody induction by vaccination can result in functionally sterile HTLV-1 protection. Results highlight the rationale for strategies aimed at anti-Env antibody induction in prophylactic HTLV-1 vaccine development.