Human Immunization With a Polymorphic Malaria Vaccine Candidate Induced Antibodies to Conserved Epitopes That Promote Functional Antibodies to Multiple Parasite Strains

Human immunization with a polymorphic malaria vaccine candidate, MSP2, induced functional cross-reactive antibodies targeting conserved epitopes. This contrasts with naturally acquired antibodies, which target polymorphic epitopes, mediating immune escape. Findings reveal potential to overcome antigenic diversity for effective malaria vaccines.

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Overcoming Antigenic Diversity by Enhancing the Immunogenicity of Conserved Epitopes on the Malaria Vaccine Candidate Apical Membrane Antigen-1

PLoS Pathogens ◽

10.1371/journal.ppat.1003840 ◽

2013 ◽

Vol 9 (12) ◽

pp. e1003840 ◽

Cited By ~ 56

Author(s):

Sheetij Dutta ◽

Lisa S. Dlugosz ◽

Damien R. Drew ◽

Xiopeng Ge ◽

Diouf Ababacar ◽

...

Keyword(s):

Malaria Vaccine ◽

Vaccine Candidate ◽

Apical Membrane ◽

Antigenic Diversity ◽

Apical Membrane Antigen 1 ◽

Apical Membrane Antigen ◽

Malaria Vaccine Candidate

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The Malaria Vaccine Candidate GMZ2 Elicits Functional Antibodies in Individuals From Malaria Endemic and Non-Endemic Areas

The Journal of Infectious Diseases ◽

10.1093/infdis/jit185 ◽

2013 ◽

Vol 208 (3) ◽

pp. 479-488 ◽

Cited By ~ 44

Author(s):

Micha Phill Grønholm Jepsen ◽

Prajakta S. Jogdand ◽

Susheel K. Singh ◽

Meral Esen ◽

Michael Christiansen ◽

...

Keyword(s):

Malaria Vaccine ◽

Vaccine Candidate ◽

Malaria Vaccine Candidate ◽

Endemic Areas ◽

Functional Antibodies

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Correction: Overcoming Antigenic Diversity by Enhancing the Immunogenicity of Conserved Epitopes on the Malaria Vaccine Candidate Apical Membrane Antigen-1

PLoS Pathogens ◽

10.1371/annotation/be0d67d1-314f-4654-8a2f-b668d1e32bbd ◽

2014 ◽

Vol 10 (1) ◽

Author(s):

Sheetij Dutta ◽

Lisa S. Dlugosz ◽

Damien R. Drew ◽

Xiaopeng Ge ◽

Diouf Ababacar ◽

...

Keyword(s):

Malaria Vaccine ◽

Vaccine Candidate ◽

Apical Membrane ◽

Antigenic Diversity ◽

Apical Membrane Antigen 1 ◽

Apical Membrane Antigen ◽

Malaria Vaccine Candidate

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Multi-functional antibodies are induced by the RTS,S malaria vaccine and associated with protection in a phase I/IIa trial

10.1101/851725 ◽

2019 ◽

Author(s):

Liriye Kurtovic ◽

Tanmaya Atre ◽

Gaoqian Feng ◽

Bruce D. Wines ◽

Jo-Anne Chan ◽

...

Keyword(s):

Malaria Vaccine ◽

Protective Efficacy ◽

Vaccine Dose ◽

Functional Activities ◽

Effector Functions ◽

Malaria Vaccines ◽

Multiple Regions ◽

Protective Antibodies ◽

Malaria Vaccine Candidate ◽

Functional Antibodies

ABSTRACTBackgroundRTS,S is the leading malaria vaccine candidate, but only confers partial efficacy against malaria in children. RTS,S is based on the major Plasmodium falciparum sporozoite surface antigen, circumsporozoite protein (CSP). The induction of anti-CSP antibodies is important for protection, however, it is unclear how protective antibodies function.MethodsWe quantified the induction of functional anti-CSP antibody responses in healthy malaria-naïve adults (N=45) vaccinated with RTS,S/AS01. This included the ability to mediate effector functions via the fragment crystallizable (Fc) region, such as interacting with human complement proteins and Fcγ-receptors (FcγRs) that are expressed on immune cells, which promote various immunological functions.ResultsOur major findings were i) RTS,S-induced antibodies mediate Fc-dependent effector functions, ii) functional antibodies were generally highest after the second vaccine dose; iii) functional antibodies targeted multiple regions of CSP, iv) participants with higher levels of functional antibodies had a reduced probability of developing parasitemia following homologous challenge (p<0.05); v) non-protected subjects had higher levels of anti-CSP IgM.ConclusionsOur data suggests a role for Fc-dependent antibody effector functions in RTS,S-induced immunity. Enhancing the induction of these functional activities may be a strategy to improve the protective efficacy of RTS,S or other malaria vaccines.

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