Effect of chemokine adjuvants on immunogenicity and cross-protective efficacy of serine repeat antigen (SERA) DNA vaccine candidate against Plasmodium berghei in mice

Abstract

Malaria remains a major global health challenge with more than 300 million reported clinical cases and between one and three million deaths per year despite concerted efforts to disrupt the mosquito-Plasmodium-human triad. This has prompted interest in developing a safe, efficacious, affordable and accessible vaccine to complement other malaria control measures. Plasmodiumderived antigens expressed during the asexual blood stage, such as serine repeat antigen (SERA), are viable vaccine candidates. It has been shown that antibodies raised against SERA inhibit growth of malaria parasites in vitro. However, there is a need to come up with safe and appropriate adjuvants to improve immunogenicity of such subunit vaccines. In this study the effect of CCL5 and CCL20 as adjuvants, on immunogenicity and cross-protective efficacy of SERA DNA vaccine was evaluated in addition to their safety, in a murine malaria model. BALB/c mice (N=132) were randomly distributed in six (6) groups which were treated as follows; SERA only (n=24), SERA+CCL5 (n=24), SERA+CCL20 (n=24), pIRES plasmid backbone (plasmid control) (n=24), Tris EDTA buffer pH 7.2 (buffer control) (n=24). The remaining 12 mice were used for pre-immunization baseline data (n=6) and non-vaccinated controls (n=6). Mice were injected with 100µg of DNA intramuscularly into each anterior quadriceps muscle in three doses at 3-week intervals (days 0, 21, and 42). Immunization did not elicit any vaccine related adverse reactions at the injection site. Low cytokine and recall responses were observed from ELISA and mononuclear cell proliferation assays respectively. Three weeks after the last immunization, mice were infected with Plasmodium berghei blood stage parasites to determine cross protective efficacy. All mice developed patent parasitaemia with the SERA+CCL5 group exhibiting parasitaemia suppression of upto 68.69% and all of the SERA+CCL20 group surviving upto 9 days post-infection. These findings show cross-protection of PfSERA in addition to illustrating potential of immunomodulatory molecules such as CCL20 and CCL5 in improving protection conferred through DNA vaccines while maintaining their safety.