Vaccines (Oct 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

  • Kartika Hardianti Zainal,
  • Ammar Abdurrahman Hasyim,
  • Yutaro Yamamoto,
  • Tetsushi Mizuno,
  • Yuna Sato,
  • Sani Hadiyan Rasyid,
  • Mamoru Niikura,
  • Yu-ichi Abe,
  • Mitsuhiro Iyori,
  • Hiroaki Mizukami,
  • Hisatoshi Shida,
  • Shigeto Yoshida

DOI
https://doi.org/10.3390/vaccines12101155
Journal volume & issue
Vol. 12, no. 10
p. 1155

Abstract

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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 transmission-blocking activity (TBA) 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.

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