Protective Immunity Induced by Virus-Like Particle Containing Merozoite Surface Protein 9 of Plasmodium berghei

Abstract

Merozoite surface protein 9 (MSP-9) from Plasmodium has shown promise as a vaccine candidate due to its location and possible role in erythrocyte invasion. In this study, we generated virus-like particles (VLPs) targeting P. berghei MSP-9, and investigated the protection against lethal doses of P. berghei in a mouse model. We found that VLP vaccination induced a P. berghei-specific IgG antibody response in the sera and CD4+ and CD8+ T cell populations in blood compared to a naïve control group. Upon challenge infection with P. berghei, vaccinated mice showed a significant increase in CD4+ and CD8+ effector memory T cell and memory B cell populations. Importantly, MSP-9 VLP immunization inhibited levels of the pro-inflammatory cytokines IFN-γ and IL-6 in the spleen and parasite replication in blood, resulting in significantly prolonged survival time. These results suggest that the MSP-9 VLP vaccine may constitute an effective malaria vaccine.

Mucosal Administration of Recombinant Baculovirus Displaying Toxoplasma gondii ROP4 Confers Protection Against T. gondii Challenge Infection in Mice

“…Endotoxin presence in the recombinant baculoviruses was checked using Pierce™ Chromogenic Endotoxin Quant Kit (Thermo Fisher Scientific, Waltham, MA, US). To characterize the expression of ROP4 in rBVs, a polyclonal mouse anti- T. gondii antibody was used to probe T. gondii ROP4 protein in rBVs by ELISA as previously described elsewhere ( Welsh, 2011 ; Lee et al., 2020 ). Briefly, wells of 96-well plates were coated with serially diluted ROP4 rBVs overnight at 4°C.…”

Influenza virus-like particle vaccine containing both apical membrane antigen 1 and microneme-associated antigen proteins of Plasmodium berghei confers protection in mice

“…In our previous study, VLPs immunizations from Toxoplasma gondii antigenic proteins or P. berghei MSP-8 and MSP-9 significantly lessened inflammatory cytokine responses [ 2 , 5 , 28 ]. Consistent with these findings, in our current study, VLP-immunized mice showed significant reductions in pro-inflammatory cytokines IFN-γ and TNF-α compared to the naïve challenge control, which may contribute to lessened parasitemia.…”

“…Plasmodium berghei ANKA strain was maintained in BALB/c mice and used for challenge infection as described previously [ 8 ]. Spodoptera frugiperda SF9 cells were used for the production of recombinant baculovirus (rBV), and virus-like particles were maintained using serum-free SF900-II medium (Invitrogen, Carlsbad, CA, USA) as described previously [ 5 ]. Plasmodium berghei -infected sera from mice were collected through retro-orbital plexus puncture.…”

“…At 6 days post-challenge infection, spleens of mice were collected and individually processed for splenocyte isolation as previously described [ 5 ]. Supernatants were collected after centrifugation at 2000 rpm for 10 min, and subsequently used to determine the level of inflammatory cytokines interferon-gamma (IFN-γ) and tumor necrosis factor-alpha (TNF-α) in spleen supernatant using the BD OptEIA IFN-γ and TNF-α ELISA kits (BD Biosciences, San Jose, CA, USA).…”

“…In 2021, the World Health Organization (WHO) recommended the use of RTS,S/AS01 recombinant protein vaccine to immunize children residing in malaria-endemic parts of the world [ 4 ]. However, given the 26–50% protection rate demonstrated by this vaccine in children during the phase 3 clinical trial [ 5 , 6 ], there is a pressing need to improve vaccine design strategy and develop a highly efficacious malaria vaccine.…”