Adeno-associated virus-based malaria booster vaccine following attenuated replication-competent vaccinia virus LC16m8Δ priming. (February 2023)

• Record Type: Journal Article
• Authors: Hasyim, Ammar A.; Iyori, Mitsuhiro; Mizuno, Tetsushi; Abe, Yu-ichi; Yamagoshi, Iroha; Yusuf, Yenni; Syafira, Intan; Sakamoto, Akihiko; Yamamoto, Yutaro; Mizukami, Hiroaki; Shida, Hisatoshi; Yoshida, Shigeto
• Is Part Of: Parasitology international. Volume 92(2023)
• Publication Date: 2023-02
• Subjects: Malaria -- Vaccine -- AAV -- Vaccinia virus -- Protection -- Transmission-blockade; Parasitology -- Periodicals; Parasites -- Periodicals; Parasitic Diseases -- Periodicals; Parasitology -- Periodicals; Parasitologie -- Périodiques; 571.99905
• DOI: 10.1016/j.parint.2022.102652
• Languages: English
• ISSNs: 1383-5769

Abstract

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. Graphical abstract: Unlabelled Image Highlights: m8Δ/AAV5-based vaccine achieves 100% protection against first sporozoite challenge. m8Δ/AAV1-based vaccine achieves 100% protection against second sporozoite challenge. m8Δ/AAV5-based vaccine confers potent malaria transmission-blocking activity. AAV5 is an alternative vaccine vector to AAV1 when re-immunization is required.