A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses
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- A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses
Forlagets udgivne version, 532 KB, PDF-dokument
Sungwa Matondo, Susan Thrane, Christoph Mikkel Janitzek, Reginald Adolph Kavishe, Steven Boniface Mwakalinga, Thor Grundtvig Theander, Ali Salanti, Morten Agertoug Nielsen, Adam Frederik Sander Pedersen
Background: 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).
Methods: 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.
Results: 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.
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.
|Tidsskrift||African Health Sciences|
|Status||Udgivet - 2017|
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