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This involved priming with a highly attenuated, replication-competent vaccinia virus strain LC16m8\u0394 (m8\u0394) and boosting with adeno-associated virus type 1 (AAV1). This approach demonstrated 100% efficacy in both protection and transmission-blocking in a murine model. In this study, we compared our LC16m8\u2206\/AAV1 vaccine, which harbors a gene encoding Pfs25-PfCSP fusion protein, to RTS,S\/AS01 (RTS,S) in terms of immune responses, protective efficacy, and transmission-blocking activity (TBA) in murine models. Methods: Mice were immunized following prime-boost vaccine regimens m8\u2206\/AAV1 or RTS,S and challenged with transgenic Plasmodium berghei parasites. Immune responses were assessed via ELISA, and TB efficacy was evaluated using direct feeding assays. Results: m8\u2206\/AAV1 provided complete protection (100%) in BALB\/c mice and moderate (40%) protection in C57BL\/6 mice, similar to RTS,S. Unlike RTS,S\u2019s narrow focus (repeat region), m8\u2206\/AAV1 triggered antibodies for all PfCSP regions (N-terminus, repeat, and C-terminus) with balanced Th1\/Th2 ratios. Regarding transmission blockade, serum from m8\u2206\/AAV1-vaccinated BALB\/c mice achieved substantial transmission-reducing activity (TRA = 83.02%) and TB activity (TBA = 38.98%)\u2014attributes not observed with RTS,S. Furthermore, m8\u2206\/AAV1 demonstrated durable TB efficacy (94.31% TRA and 63.79% TBA) 100 days post-immunization. Conclusions: These results highlight m8\u2206\/AAV1\u2032s dual action in preventing sporozoite invasion and onward transmission, a significant advantage over RTS,S. Consequently, m8\u2206\/AAV1 represents an alternative and a promising vaccine candidate that can enhance malaria control and elimination strategies.<\/jats:p>","DOI":"10.3390\/vaccines12101155","type":"journal-article","created":{"date-parts":[[2024,10,10]],"date-time":"2024-10-10T12:57:47Z","timestamp":1728565067000},"page":"1155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1-Based Malaria Vaccine versus RTS,S\/AS01 in Murine Models"],"prefix":"10.3390","volume":"12","author":[{"given":"Kartika Hardianti","family":"Zainal","sequence":"first","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2799-1652","authenticated-orcid":false,"given":"Ammar Abdurrahman","family":"Hasyim","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"},{"name":"Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta 10430, Indonesia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yutaro","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3687-0174","authenticated-orcid":false,"given":"Tetsushi","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"},{"name":"Department of Global Infectious Diseases, Graduate School of Medical Sciences, Kanazawa University, Kanazawa 920-0934, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuna","family":"Sato","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sani Hadiyan","family":"Rasyid","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mamoru","family":"Niikura","sequence":"additional","affiliation":[{"name":"School of Life and Environmental Science, Azabu University, Sagamihara 252-5201, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-ichi","family":"Abe","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9940-7342","authenticated-orcid":false,"given":"Mitsuhiro","family":"Iyori","sequence":"additional","affiliation":[{"name":"Research Institute of Pharmaceutical Sciences, Musashino University, Tokyo 202-8585, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Division of Gene Therapy, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisatoshi","family":"Shida","sequence":"additional","affiliation":[{"name":"Laboratory of Primate Model, Research Center for Infectious Diseases, Institute for Frontier Life and Medical Science, Kyoto University, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8018-381X","authenticated-orcid":false,"given":"Shigeto","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Laboratory of Vaccinology and Applied Immunology, School of Pharmacy, Kanazawa University, Kanazawa 920-1192, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,10]]},"reference":[{"key":"ref_1","unstructured":"Jamison, D.T., Feachem, R.G., Makgoba, M.W., Bos, E.R., Baingana, F.K., Hofman, K.J., and Rogo, K.O. 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