Adeno-associated virus-based malaria booster vaccine following attenuated replication-competent vaccinia virus LC16m8Δ priming |
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| Institution: | 1. Laboratory of Vaccinology and Applied Immunology, Kanazawa University School of Pharmacy, Kanazawa, Ishikawa 920-1192, Japan;2. Department of Global Infectious Diseases, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Ishikawa 920-0934, Japan;3. Division of Gene Therapy, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan;4. Department of Parasitology, Faculty of Medicine, Hasanuddin University, Makassar, Sulawesi Selatan 90245, Indonesia;5. Institute for Genetic Medicine, Hokkaido University, Sapporo, Hokkaido 060-0815, Japan;1. Laboratory of Veterinary Microbiology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan;2. Laboratory of Veterinary Parasitology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan;3. Beehive Japan Co., Ltd., Tokyo 152-0003, Japan;1. Department of Parasitology, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka;2. CSIR-Indian Institute of Chemical Biology, Kolkata, West Bengal 700032, India;3. Department of Biochemistry and Molecular Biology, Faculty of Medicine, University of Colombo, Colombo 00800, Sri Lanka;1. Russian Federal Research Institute of Fisheries and Oceanography, Okruzhnoy Pr. 19, 105187 Moscow, Russia;2. Lomonosov Moscow State University, Leninskiye Gory 1, 119234 Moscow, Russia;3. Moscow representative office of A.O. Kovalevsky Institute of Biology of the Southern Seas of RAS, Leninsky Pr. 38/3, Moscow 119991, Russia;1. Severtsov Institute of Ecology and Evolution, Russian Academy of Sciences, 119071 Moscow, Russia;2. Institute of Biology, Karelian Research Centre, Russian Academy of Sciences, 185035 Petrozavodsk, Russia;3. Department of Zoology and Ecology, Petrozavodsk State University, 185910 Petrozavodsk, Russia;1. Guangdong Provincial Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, PR China;2. Guangzhou Chest hospital, Guangzhou, PR China;3. School of Life Science and Biopharmaceuticals, Guangdong Pharmaceutical University, Guangzhou, PR China;4. Division of Experimental Medicine, Department of Medicine, McGill University, Montreal, QC, Canada;1. Department of Microbiology, University of Medicine 1, No. 245, Myoma Kyaung Street, Lanmadaw Township, Yangon, Myanmar;2. Division of Parasitology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan;3. Department of Parasitology, Faculty of Veterinary Medicine, Vietnam National University of Agriculture, Hanoi 12406, Viet Nam;4. Hirakawa Zoological Park, 5669-1 Hirakawa-cho, Kagoshima-shi, Japan;5. Koshima Field Station, Wildlife Research Center, Kyoto University, 16-1 Ichiki, Kushima, Miyazaki 889-3311, Japan;6. Yokohama Zoological Gardens Zoorasia, 1171-1, Kami-Shirane-cho, Yokohama 241-0001, Japan;7. Laboratory of Veterinary Parasitic Diseases, Department of Veterinary Sciences, Faculty of Agriculture, University of Miyazaki, 1-1 Gakuen-kibanadai-nishi, 889-2192 Miyazaki, Japan;8. Center for Animal Disease Control, University of Miyazaki, 1-1 Gakuen-kibanadai-nishi, 889-2192 Miyazaki, Japan |
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| Abstract: | We previously demonstrated that boosting with adeno-associated virus (AAV) type 1 (AAV1) can induce highly effective and long-lasting protective immune responses against malaria parasites when combined with replication-deficient adenovirus priming in a rodent model. In the present study, we compared the efficacy of two different AAV serotypes, AAV1 and AAV5, as malaria booster vaccines following priming with the attenuated replication-competent vaccinia virus strain LC16m8Δ (m8Δ), which harbors the fusion gene encoding both the pre-erythrocytic stage protein, Plasmodium falciparum circumsporozoite (PfCSP) and the sexual stage protein (Pfs25) in a two-dose heterologous prime-boost immunization regimen. Both regimens, m8Δ/AAV1 and m8Δ/AAV5, induced robust anti-PfCSP and anti-Pfs25 antibodies. To evaluate the protective efficacy, the mice were challenged with sporozoites twice after immunization. At the first sporozoite challenge, m8Δ/AAV5 achieved 100% sterile protection whereas m8Δ/AAV1 achieved 70% protection. However, at the second challenge, 100% of the surviving mice from the first challenge were protected in the m8Δ/AAV1 group whereas only 55.6% of those in the m8Δ/AAV5 group were protected. Regarding the transmission-blocking efficacy, we found that both immunization regimens induced high levels of transmission-reducing activity (>99%) and transmission-blocking activity (>95%). Our data indicate that the AAV5-based multistage malaria vaccine is as effective as the AAV1-based vaccine when administered following an m8Δ-based vaccine. These results suggest that AAV5 could be a viable alternate vaccine vector as a malaria booster vaccine. |
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