Version 1
: Received: 18 September 2024 / Approved: 18 September 2024 / Online: 18 September 2024 (11:32:27 CEST)
How to cite:
Zainal, K. H.; Hasyim, A. A.; Yamamoto, Y.; Mizuno, T.; Sato, Y.; Rasyid, S. H.; Niikura, M.; Abe, Y.-I.; Iyori, M.; Mizukami, H.; Shida, H.; Yoshida, S. A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1- based Malaria Vaccine versus RTS,S/AS01 in Murine Models. Preprints2024, 2024091398. https://doi.org/10.20944/preprints202409.1398.v1
Zainal, K. H.; Hasyim, A. A.; Yamamoto, Y.; Mizuno, T.; Sato, Y.; Rasyid, S. H.; Niikura, M.; Abe, Y.-I.; Iyori, M.; Mizukami, H.; Shida, H.; Yoshida, S. A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1- based Malaria Vaccine versus RTS,S/AS01 in Murine Models. Preprints 2024, 2024091398. https://doi.org/10.20944/preprints202409.1398.v1
Zainal, K. H.; Hasyim, A. A.; Yamamoto, Y.; Mizuno, T.; Sato, Y.; Rasyid, S. H.; Niikura, M.; Abe, Y.-I.; Iyori, M.; Mizukami, H.; Shida, H.; Yoshida, S. A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1- based Malaria Vaccine versus RTS,S/AS01 in Murine Models. Preprints2024, 2024091398. https://doi.org/10.20944/preprints202409.1398.v1
APA Style
Zainal, K. H., Hasyim, A. A., Yamamoto, Y., Mizuno, T., Sato, Y., Rasyid, S. H., Niikura, M., Abe, Y. I., Iyori, M., Mizukami, H., Shida, H., & Yoshida, S. (2024). A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1- based Malaria Vaccine versus RTS,S/AS01 in Murine Models. Preprints. https://doi.org/10.20944/preprints202409.1398.v1
Chicago/Turabian Style
Zainal, K. H., Hisatoshi Shida and Shigeto Yoshida. 2024 "A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1- based Malaria Vaccine versus RTS,S/AS01 in Murine Models" Preprints. https://doi.org/10.20944/preprints202409.1398.v1
Abstract
Background/objectives: We developed a multistage Plasmodium falciparum vaccine using a heterologous prime-boost immunization strategy. This involved priming with a highly attenuated, replication-competent vaccinia virus strain LC16m8Δ (m8Δ) 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∆/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 TB activity in murine models. Methods: Mice were immunized following prime-boost vaccine regimens m8∆/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∆/AAV1 provided complete protection (100%) in BALB/c mice and moderate (40%) protection in C57BL/6 mice, similar to RTS,S. Unlike RTS,S’s narrow focus (repeat region), m8∆/AAV1 triggered antibodies for all PfCSP regions (N-terminus, repeat, and C-terminus) with balanced Th1/Th2 ratios. Regarding transmission blockade, serum from m8∆/AAV1-vaccinated BALB/c mice achieved substantial transmission-reducing activity (TRA = 83.02%) and TB activity (TBA = 38.98%)—attributes not observed with RTS,S. Furthermore, m8∆/AAV1 demonstrated durable TB efficacy (94.31% TRA and 63.79% TBA) 100 days post-immunization. Conclusions: These results highlight m8∆/AAV1's dual action in preventing sporozoite invasion and onward transmission, a significant advantage over RTS,S. Consequently, m8∆/AAV1 represents an alternative and a promising vaccine candidate that can enhance malaria control and elimination strategies.
Keywords
malaria; vaccine; RTS,S; LC16m8∆; AAV; efficacy
Subject
Biology and Life Sciences, Immunology and Microbiology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
