Protection and Alleviated Inflammation Induced by Virus-like Particle Vaccines Containing Plasmodium berghei MSP-8, MSP-9 and RAP1.

Su-Hwa Lee,Fu-Shi Quan,Hae-Ji Kang,Ki-Back Chu

doi:10.3390/vaccines10020203

Su-Hwa Lee, Fu-Shi Quan + Show 2 more

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https://doi.org/10.3390/vaccines10020203

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Abstract

Virus-like particles (VLP) are a highly efficient vaccine platform used to present multiple antigenic proteins. Merozoite surface protein 8 (MSP-8), 9 (MSP-9) and rhoptry-associated protein 1 (RAP1) of Plasmodium berghei are the important proteins in erythrocyte invasion and the replication of parasites. In this study, we generated three VLPs expressing MSP-8, MSP-9 or RAP1 together with influenza virus matrix protein M1 as a core protein, and the protection and alleviated inflammation induced by VLP immunization were investigated. Mice were immunized with a mixture of three VLPs, MSP-8, MSP-9 and RAP1, and challenge-infected with P. berghei. As a result, VLPs immunization elicited higher levels of P. berghei or VLPs-specific IgG antibody responses in the sera upon boost compared to that upon prime and naive. Upon challenge infection with P. berghei, higher levels of CD4+ T cell and memory B cell responses in the spleen were also found in VLPs-immunized mice compared to non-immunized control. Importantly, VLP immunization significantly alleviated inflammatory cytokine responses (TNF-α, IFN-γ) both in the sera and spleen. VLP vaccine immunization also assisted in diminishing the parasitic burden in the peripheral blood and prolonged the survival of immunized mice. These results indicated that a VLPs vaccine containing MSP-8, MSP-9 and RAP1 could be a vaccine candidate for P. berghei infection.

Highlights

Malaria caused by the Plasmodium parasite remains a serious disease threatening public health
Sf9 cells were co-infected with Recombinant baculovirus (rBV) expressing P. berghei rhoptry-associated protein 1 (RAP1) and influenza matrix protein 1 (M1) to generate RAP1 Virus-like particles (VLP)
Merozoite surface protein 8 (MSP-8), merozoite surface proteins (MSP)-9 or RAP1 VLPs displayed a spherical morphology with spikes on their surfaces

Summary

Introduction

Malaria caused by the Plasmodium parasite remains a serious disease threatening public health. In 2016, significant funds were invested to implement a malaria control and elimination program, which helped to reduce the burden of malaria disease [1]. Since malaria continues to cause enormous loss of life across world, there is a need for the introduction of a treatment that can prevent malaria, such as a vaccine [3]. Infection by the Plasmodium parasite can lead to death due to the severity of symptoms caused by inflammation [7,8,9]. Because the pathological symptoms of malaria disease begin to appear at the blood stage, we prioritized limiting the invasion of parasites in erythrocytes and the growth of invading parasites in vaccine design [10,11]

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