Apical membrane antigen 1: a malaria vaccine candidate in review

Remarque, Edmond J.; Faber, Bart W.; Kocken, Clemens H. M.; Thomas, Alan W.

doi:10.1016/j.pt.2007.12.002

Cited by 246 publications

(269 citation statements)

References 81 publications

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“…The AMA1 vaccine field has suffered from the polymorphic nature of this Ag, as well as the fact that vaccine-induced Abs inhibit growth in a vaccine-allele-specific manner (6). The IgG induced in this study by the 3D7 and FVO biallelic vaccines showed correspondingly high-level GIA against the 3D7 and FCR3 vaccine strains, especially after the AdCh63-MVA-protein and AdCh63-protein immunization regimens.…”

Section: Discussionmentioning

confidence: 57%

“…One study showed an important role for CD4 + T cells against AMA1 in mediating efficacy against blood-stage P. chabaudi infection in mice (13). The induction of such responses against epitopes within AMA1 that are common to multiple alleles bodes well for human immunization if such strain-transcending CD4 + T cells contribute significantly to protection in humans, especially given the issues surrounding the allele-specific protective effects of IgG against this Ag (6).…”

Section: Discussionmentioning

confidence: 99%

“…Blood-stage malaria vaccine development has classically focused on recombinant protein-in-adjuvant formulations, with the aim of inducing high-titer growth-inhibitory Abs against merozoite Ags involved in erythrocyte invasion, such as the widely studied merozoite surface protein 1 (MSP1) (5) and apical membrane Ag 1 (AMA1) (6). In recent years, viral-vectored blood-stage malaria vaccines have also been developed (7,8).…”

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confidence: 99%

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Enhancing Blood-Stage Malaria Subunit Vaccine Immunogenicity in Rhesus Macaques by Combining Adenovirus, Poxvirus, and Protein-in-Adjuvant Vaccines

Draper

Biswas

Spencer

et al. 2010

The Journal of Immunology

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108

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Protein-in-adjuvant formulations and viral-vectored vaccines encoding blood-stage malaria Ags have shown efficacy in rodent malaria models and in vitro assays against Plasmodium falciparum. Abs and CD4+ T cell responses are associated with protective efficacy against blood-stage malaria, whereas CD8+ T cells against some classical blood-stage Ags can also have a protective effect against liver-stage parasites. No subunit vaccine strategy alone has generated demonstrable high-level efficacy against blood-stage infection in clinical trials. The induction of high-level Ab responses, as well as potent T and B cell effector and memory populations, is likely to be essential to achieve immediate and sustained protective efficacy in humans. This study describes in detail the immunogenicity of vaccines against P. falciparum apical membrane Ag 1 in rhesus macaques (Macaca mulatta), including the chimpanzee adenovirus 63 (AdCh63), the poxvirus modified vaccinia virus Ankara (MVA), and protein vaccines formulated in Alhydrogel or CoVaccine HT adjuvants. AdCh63-MVA heterologous prime-boost immunization induces strong and long-lasting multifunctional CD8+ and CD4+ T cell responses that exhibit a central memory-like phenotype. Three-shot (AdCh63-MVA-protein) or two-shot (AdCh63-protein) regimens induce memory B cells and high-titer functional IgG responses that inhibit the growth of two divergent strains of P. falciparum in vitro. Prior immunization with adenoviral vectors of alternative human or simian serotype does not affect the immunogenicity of the AdCh63 apical membrane Ag 1 vaccine. These data encourage the further clinical development and coadministration of protein and viral vector vaccine platforms in an attempt to induce broad cellular and humoral immune responses against blood-stage malaria Ags in humans.

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Enhancing Blood-Stage Malaria Subunit Vaccine Immunogenicity in Rhesus Macaques by Combining Adenovirus, Poxvirus, and Protein-in-Adjuvant Vaccines

Draper

Biswas

Spencer

et al. 2010

The Journal of Immunology

Self Cite

108

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“…The malaria vaccine candidate AMA1 is a subunit-based vaccine against P. falciparum that induces protection (37), but only against parasite strains that are closely related to the vaccine (38)(39)(40). A recent phase 2b AMA1 vaccine trial in 1-6-y-old children in Mali found 64% efficacy against malaria caused by vaccine-like strains, underscoring its potential as a malaria vaccine (41).…”

mentioning

confidence: 99%

Simulation of B Cell Affinity Maturation Explains Enhanced Antibody Cross-Reactivity Induced by the Polyvalent Malaria Vaccine AMA1

Chaudhury

Reifman

Wallqvist

2014

The Journal of Immunology

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Polyvalent vaccines use a mixture of Ags representing distinct pathogen strains to induce an immune response that is cross-reactive and protective. However, such approaches often have mixed results, and it is unclear how polyvalency alters the fine specificity of the Ab response and what those consequences might be for protection. In this article, we present a coarse-grain theoretical model of B cell affinity maturation during monovalent and polyvalent vaccinations that predicts the fine specificity and cross-reactivity of the Ab response. We stochastically simulate affinity maturation using a population dynamics approach in which the host B cell repertoire is represented explicitly, and individual B cell subpopulations undergo rounds of stimulation, mutation, and differentiation. Ags contain multiple epitopes and are present in subpopulations of distinct pathogen strains, each with varying degrees of cross-reactivity at the epitope level. This epitope- and strain-specific model of affinity maturation enables us to study the composition of the polyclonal response in granular detail and identify the mechanisms driving serum specificity and cross-reactivity. We applied this approach to predict the Ab response to a polyvalent vaccine based on the highly polymorphic malaria Ag apical membrane antigen-1. Our simulations show how polyvalent apical membrane Ag-1 vaccination alters the selection pressure during affinity maturation to favor cross-reactive B cells to both conserved and strain-specific epitopes and demonstrate how a polyvalent vaccine with a small number of strains and only moderate allelic coverage may be broadly neutralizing. Our findings suggest that altered fine specificity and enhanced cross-reactivity may be a universal feature of polyvalent vaccines.

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“…In Plasmodium species, AMA1 is maximally expressed during the formation of merozoites in late schizogony, targeted to the microneme apical organelles and secreted onto the surface of the merozoite at the time of invasion of the host erythrocyte. AMA1-based vaccines provide protection against malaria challenge in animal models (reviewed by Remarque), 240 induce antibodies which inhibit the growth of P. falciparum in culture 241 and correlate with protection against clinical malaria in endemic areas. [242][243][244] AMA1 is also expressed in the sporozoite and liver stages of the parasite, 245 raising the possibility that immune responses to this antigen could simultaneously protect against multiple stages of the parasite life cycle.…”

Section: Antigen Designmentioning

confidence: 99%