TY - JOUR
T1 - A VAR2CSA:CSP conjugate capable of inducing dual specificity antibody responses
AU - Matondo, Sungwa
AU - Thrane, Susan
AU - Janitzek, Christoph Mikkel
AU - Kavishe, Reginald Adolph
AU - Mwakalinga, Steven Boniface
AU - Theander, Thor Grundtvig
AU - Salanti, Ali
AU - Nielsen, Morten Agertoug
AU - Pedersen, Adam Frederik Sander
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
KW - Bacterial superglue
KW - Circumsporozoite protein
KW - CSP-SpyCatcher
KW - DBL1x-DBL2x-ID2a:CSP conjugate
KW - Malaria vaccine
KW - SpyTag-DBL1x-DBL2x-ID2a
KW - VAR2CSA
U2 - 10.4314/ahs.v17i2.11
DO - 10.4314/ahs.v17i2.11
M3 - Journal article
C2 - 29062332
AN - SCOPUS:85025104873
SN - 1680-6905
VL - 17
SP - 373
EP - 381
JO - African Health Sciences
JF - African Health Sciences
IS - 2
ER -
