A Head-to-Head Comparative Study of the Replication-Competent Vaccinia Virus and AAV1-Based Malaria Vaccine versus RTS,S/AS01 in Murine Models

• Published in: Vaccines (Basel) Vol. 12; no. 10; p. 1155
• Main Authors: Zainal, Kartika Hardianti, Hasyim, Ammar Abdurrahman, Yamamoto, Yutaro, Mizuno, Tetsushi, Sato, Yuna, Rasyid, Sani Hadiyan, Niikura, Mamoru, Abe, Yu-Ichi, Iyori, Mitsuhiro, Mizukami, Hiroaki, Shida, Hisatoshi, Yoshida, Shigeto
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 10.10.2024; MDPI
• Subjects: AAV; Adjuvants; Animal models; C-Terminus; Comparative studies; Disease transmission; Effectiveness; efficacy; Enzyme-linked immunosorbent assay; Enzymes; Fusion protein; Gene fusion; Immune response; Immunization; Infections; LC16m8; Lymphocytes T; Malaria; Mosquitoes; N-Terminus; Parasites; Proteins; Replication; RTS,S; vaccine; Vaccines; Vector-borne diseases; Viruses; Belgium; Japan; LC16m8; RTS,S; vaccine; malaria; AAV; efficacy
• ISSN: 2076-393X; 2076-393X
• DOI: 10.3390/vaccines12101155

: We developed a multistage 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. Mice were immunized following prime-boost vaccine regimens m8∆/AAV1 or RTS,S and challenged with transgenic parasites. Immune responses were assessed via ELISA, and TB efficacy was evaluated using direct feeding assays. : 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. : 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.