Assessment of humoral immune responses in malaria vaccine trials

AbstractPlasmodium falciparum apical membrane antigen 1 (PfAMA1) is a candidate malaria vaccine antigen expressed on merozoites and sporozoites. PfAMA1’s polymorphic nature impacts vaccine-induced protection. To address polymorphism, three Diversity Covering (DiCo) protein sequences were designed and tested in a staggered phase Ia/b trial. A cohort of malaria-naive adults received PfAMA1-DiCo adjuvanted with Alhydrogel® or GLA-SE and a cohort of malaria-exposed adults received placebo or GLA-SE adjuvanted PfAMA1 DiCo at weeks 0, 4 and 26. IgG and GIA levels measured 4 weeks after the third vaccination are similar in malaria-naive volunteers and placebo-immunised malaria-exposed adults, and have a similar breadth. Vaccination of malaria-exposed adults results in significant antibody level increases to the DiCo variants, but not to naturally occurring PfAMA1 variants. Moreover, GIA levels do not increase following vaccination. Future research will need to focus on stronger adjuvants and/or adapted vaccination regimens, to induce potentially protective responses in the target group of the vaccine.

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Cellular and humoral immune responses against the Plasmodium vivax MSP-119 malaria vaccine candidate in individuals living in an endemic area in north-eastern Amazon region of Brazil

Malaria Journal ◽

10.1186/1475-2875-12-326 ◽

2013 ◽

Vol 12 (1) ◽

pp. 326 ◽

Cited By ~ 14

Author(s):

Evelyn KP Riccio ◽

Paulo RR Totino ◽

Lilian R Pratt-Riccio ◽

Vitor Ennes-Vidal ◽

Irene S Soares ◽

...

Keyword(s):

Immune Responses ◽

Plasmodium Vivax ◽

Endemic Area ◽

Malaria Vaccine ◽

Vaccine Candidate ◽

Amazon Region ◽

Humoral Immune ◽

Humoral Immune Responses ◽

North Eastern ◽

Malaria Vaccine Candidate

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Analysis of Humoral Immune Responses in Vaccine Trials

Handbook of Cancer Vaccines ◽

10.1007/978-1-59259-680-5_36 ◽

2004 ◽

pp. 543-561 ◽

Cited By ~ 1

Author(s):

Rajasekharan Somasundaram ◽

Tianqian Zhang ◽

Dorothee Herlyn

Keyword(s):

Immune Responses ◽

Humoral Immune ◽

Humoral Immune Responses ◽

Vaccine Trials

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Breadth of humoral immune responses to the C-terminus of the circumsporozoite protein is associated with protective efficacy induced by the RTS,S malaria vaccine

10.1101/2020.11.15.20232033 ◽

2020 ◽

Author(s):

Sidhartha Chaudhury ◽

Randall S. MacGill ◽

Angela M. Early ◽

Jessica S. Bolton ◽

C. Richter King ◽

...

Keyword(s):

Immune Responses ◽

Malaria Vaccine ◽

Protective Efficacy ◽

Cross Reactivity ◽

Antibody Responses ◽

Circumsporozoite Protein ◽

Humoral Immune ◽

Humoral Immune Responses ◽

C Terminus ◽

Fold Reduction

AbstractThe circumsporozoite protein (CSP) is the main surface antigen of malaria sporozoites and a prime vaccine target. Responses induced by the CSP-based RTS,S vaccine towards the polymorphic C-terminal region of P.falciparum-CSP raise concerns that vaccines using single alleles may have lower efficacy against genotypic variants. We characterized the extent of C-terminal cross-reactivity of antibodies induced by RTS,S (based on the 3D7 allele) with variants representing seven circulating field isolates through a novel HTS-multiplex assay for screening closely related peptides. Reactivity to variants showed approximately 30-fold reduction in recognition relative to 3D7. The degree of reduced cross-reactivity,ranging from 21 to 69-fold, directly correlated with the number of polymorphisms between variants and 3D7. Surprisingly, protection assessed by challenge with 3D7 parasites was strongly associated with higher C-terminal antibody breadth suggesting that C-terminal specific avidity or fine-specificity may play a role in RTS,S/AS01B-mediated protection and that breadth of C-terminal CSP-specific antibody responses may be a marker of protection.

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