Abstract
Vaccine antigens targeting specific P. falciparum parasite stages are under pre-clinical and clinical development. It seems plausible that vaccine with multiple specificities will offer higher protection. With this hypothesis, we exploited the Spy-Tag/SpyCatcher conjugation system to make a, post expression, dual antigen conjugate vaccine, comprising two clinically tested antigen candidates (CSP and VAR2CSA). The DBL1x-DBL2x-ID2a region of VAR2CSA was genetically fused with SpyTag at N-terminus. The full-length CSP antigen was genetically fused to C-terminal SpyCatcher peptide. The covalent interaction between SpyTag/SpyCatcher enables the formation of DBL1x-DBL2x-ID2a:CSP conjugate vaccine. Immunogenicity and quality of antibody responses induced by the conjugate vaccine, as well as a control CSP-SpyCatcher vaccine, was tested in BALB/c mice. Serum samples obtained from mice immunized with the conjugate vaccine were able to recognize both untagged DBL1x-DBL2x-ID2a as well as CSP antigen. Moreover, the geometric mean anti-CSP antibody titer was 1.9-fold higher in serum (at day 35 and 55 post-first immunization) from mice immunized with the conjugate vaccine, as compared to mice receiving the control vaccine. The data obtained in this study serves as proof-of-concept for the simultaneous induction of antibodies directed against individual antigen components in a dual stage anti-malaria vaccine.
Highlights
Plasmodium falciparum malaria remains a major public health problem as it continues to claim hundreds of thousands of lives globally each year
Immunogenicity of VAR2CSA:circumsporozoite protein (CSP) and CSP-SpyCatcher vaccine Antibodies in serum from mice immunized with both the dual antigen conjugate vaccine and the CSP-SpyCatcher vaccine reacted with untagged CSP antigen coated on enzyme-linked immunosorbent assay (ELISA) plate (Fig. 2a), and full-bleed sera from mice immunized with the conjugate vaccine were able to recognize untagged DBL1x-DBL2x-ID2a antigen (Fig. 2b)
The geometric mean endpoint titres of anti-CSP antibodies in the DBL1x-DBL2x-ID2a:CSP conjugate vaccine immunized group were slightly higher on days 35, 49 as well as 55 (Fig. 3), as compared to the CSP-SpyCatcher immunized group, but the difference was not statistically significant for any of the days (p=0.20, p=0.27 and p=0.27 respectively)
Summary
Plasmodium falciparum malaria remains a major public health problem as it continues to claim hundreds of thousands of lives globally each year. Several measures have been taken by WHO to fight the disease, such as the use of long-lasting insecticide-treated nets (LLINs), It is reasonable to assume that a malaria vaccine targeting multiple stages of the parasite’s life cycle will have increased efficacy. Such multistage vaccines are ideally constructed as genetic fusions to avoid multiple productions and stability testing. It seems plausible that vaccine with multiple specificities will offer higher protection With this hypothesis, we exploited the SpyTag/SpyCatcher conjugation system to make a, post expression, dual antigen conjugate vaccine, comprising two clinically tested antigen candidates (CSP and VAR2CSA). Conclusion: The data obtained in this study serves as proof-of-concept for the simultaneous induction of antibodies directed against individual antigen components in a dual stage anti-malaria vaccine
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