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.
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.
Authors: Selidji Todagbe Agnandji; Bertrand Lell; Solange Solmeheim Soulanoudjingar; José Francisco Fernandes; Béatrice Peggy Abossolo; Cornelia Conzelmann; Barbara Gaelle Nfono Ondo Methogo; Yannick Doucka; Arnaud Flamen; Benjamin Mordmüller; Saadou Issifou; Peter Gottfried Kremsner; Jahit Sacarlal; Pedro Aide; Miguel Lanaspa; John J Aponte; Arlindo Nhamuave; Diana Quelhas; Quique Bassat; Sofia Mandjate; Eusébio Macete; Pedro Alonso; Salim Abdulla; Nahya Salim; Omar Juma; Mwanajaa Shomari; Kafuruki Shubis; Francisca Machera; Ali Said Hamad; Rose Minja; Ali Mtoro; Alma Sykes; Saumu Ahmed; Alwisa Martin Urassa; Ali Mohammed Ali; Grace Mwangoka; Marcel Tanner; Halidou Tinto; Umberto D'Alessandro; Hermann Sorgho; Innocent Valea; Marc Christian Tahita; William Kaboré; Sayouba Ouédraogo; Yara Sandrine; Robert Tinga Guiguemdé; Jean Bosco Ouédraogo; Mary J Hamel; Simon Kariuki; Chris Odero; Martina Oneko; Kephas Otieno; Norbert Awino; Jackton Omoto; John Williamson; Vincent Muturi-Kioi; Kayla F Laserson; Laurence Slutsker; Walter Otieno; Lucas Otieno; Otsyula Nekoye; Stacey Gondi; Allan Otieno; Bernhards Ogutu; Ruth Wasuna; Victorine Owira; David Jones; Agnes Akoth Onyango; Patricia Njuguna; Roma Chilengi; Pauline Akoo; Christine Kerubo; Jesse Gitaka; Charity Maingi; Trudie Lang; Ally Olotu; Benjamin Tsofa; Philip Bejon; Norbert Peshu; Kevin Marsh; Seth Owusu-Agyei; Kwaku Poku Asante; Kingsley Osei-Kwakye; Owusu Boahen; Samuel Ayamba; Kingsley Kayan; Ruth Owusu-Ofori; David Dosoo; Isaac Asante; George Adjei; George Adjei; Daniel Chandramohan; Brian Greenwood; John Lusingu; Samwel Gesase; Anangisye Malabeja; Omari Abdul; Hassan Kilavo; Coline Mahende; Edwin Liheluka; Martha Lemnge; Thor Theander; Chris Drakeley; Daniel Ansong; Tsiri Agbenyega; Samuel Adjei; Harry Owusu Boateng; Theresa Rettig; John Bawa; Justice Sylverken; David Sambian; Alex Agyekum; Larko Owusu; Francis Martinson; Irving Hoffman; Tisungane Mvalo; Portia Kamthunzi; Ruthendo Nkomo; Albans Msika; Allan Jumbe; Nelecy Chome; Dalitso Nyakuipa; Joseph Chintedza; W Ripley Ballou; Myriam Bruls; Joe Cohen; Yolanda Guerra; Erik Jongert; Didier Lapierre; Amanda Leach; Marc Lievens; Opokua Ofori-Anyinam; Johan Vekemans; Terrell Carter; Didier Leboulleux; Christian Loucq; Afiya Radford; Barbara Savarese; David Schellenberg; Marla Sillman; Preeti Vansadia Journal: N Engl J Med Date: 2011-10-18 Impact factor: 91.245
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Authors: Thomas M Clausen; Stig Christoffersen; Madeleine Dahlbäck; Annette Eva Langkilde; Kamilla E Jensen; Mafalda Resende; Mette Ø Agerbæk; Daniel Andersen; Besim Berisha; Sisse B Ditlev; Vera V Pinto; Morten A Nielsen; Thor G Theander; Sine Larsen; Ali Salanti Journal: J Biol Chem Date: 2012-05-08 Impact factor: 5.157
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Authors: Katherine E Wright; Kathryn A Hjerrild; Jonathan Bartlett; Alexander D Douglas; Jing Jin; Rebecca E Brown; Joseph J Illingworth; Rebecca Ashfield; Stine B Clemmensen; Willem A de Jongh; Simon J Draper; Matthew K Higgins Journal: Nature Date: 2014-08-17 Impact factor: 49.962