| dc.description.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. | en |
