Immunogenicity of a recombinant malaria vaccine candidate, domain I+II of AMA-1 ectodomain, from Indian P. falciparum alleles

Lalitha, P.V.; Biswas, Subrata; Pillai, C. R.; Saxena, Rajiv K.

doi:10.1016/j.vaccine.2008.06.031

Cited by 6 publications

(5 citation statements)

References 47 publications

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“…Our in vivo observations are consistent with previous results showing that immunization of rhesus monkeys with only one of two PfAMA-1 variants is sufficient to induce cross-protective antibody responses as measured by GIA and ELISA assays in vitro [52]. Our results are also consistent with another study which demonstrated that mice and rabbits immunized with two allelic variants of domain I and II of the full length AMA-1 ectodomain from Indian P. falciparum isolates were able to inhibit in vitro parasite growth, but to no greater extent than with either of the allelic variants alone [53].…”

Section: Discussionsupporting

confidence: 92%

“…Another group immunized mice and rabbits with two allelic variants of domain I and II of AMA-1 ectodomain from P. falciparum isolates. The anti-AMA-1 antibodies obtained with both proteins were active in an in vitro parasite growth invasion/inhibition assay, but to no greater extent than with either of the variants alone [53]. Together these results have raised questions about the necessity of using multi-allele vaccines.…”

Section: Introductionmentioning

confidence: 99%

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Mixed allele malaria vaccines: Host protection and within-host selection

Barclay

Chan

Anders

et al. 2008

Vaccine

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Malaria parasites are frequently polymorphic at the antigenic targets of many candidate vaccines, presumably as a consequence of selection pressure from protective immune responses. Conventional wisdom is therefore that vaccines directed against a single variant could select for non-target variants, rendering the vaccine useless. Many people have argued that a solution is to develop vaccines containing the products of more than one variant of the target. However, we are unaware of any evidence that multi-allele vaccines better protect hosts against parasites or morbidity. Moreover, selection of antigen-variants is not the only evolution that could occur in response to vaccination. Increased virulence could also be favored if more aggressive strains are less well controlled by vaccine-induced immunity. Virulence and antigenic identity have been confounded in all studies so far, and so we do not know formally from any animal or human studies whether vaccine failure has been due to evasion of protective responses by variants at target epitopes, or whether vaccines are just less good at protecting against more aggressive strains.Using the rodent malaria model Plasmodium chabaudi and recombinant apical membrane antigen-1 (AMA-1), we tested whether a bi-allelic vaccine afforded greater protection from parasite infection and morbidity than did vaccination with the component alleles alone. We also tested the effect of mono- and bi-allelic vaccination on within-host selection of mixed P. chabaudi infections, and whether parasite virulence mediates pathogen titres in immunized hosts. We found that vaccination with the bi-allelic AMA-1 formulation did not afford the host greater protection from parasite infection or morbidity than did mono-allelic AMA-1 immunization. Mono-allelic immunization increased the frequency of heterologous clones in mixed clone infections. There was no evidence that any type of immunization regime favored virulence. A single AMA-1 variant is a component of candidate malaria vaccines current in human trials; our results suggest that adding extra AMA-1 alleles to these vaccines would not confer clinical benefits, but that that mono-allelic vaccines could alter AMA-1 allele frequencies in natural populations.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Mixed allele malaria vaccines: Host protection and within-host selection

Barclay

Chan

Anders

et al. 2008

Vaccine

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“…Interestingly, it has been previously identified as the major target of the invasion-inhibitory monoclonal antibody (25,(27)(28)(29) and the invasion-inhibitory peptide (30,31). Therefore, it is likely that domains I and II are the predominant targets for inhibitory responses and immunogenicity (32)(33)(34).…”

Section: Introductionmentioning

confidence: 99%

Immunization of Cattle With Recombinant Structural Ectodomains I and II of Babesia bovis Apical Membrane Antigen 1 [BbAMA-1(I/II)] Induces Strong Th1 Immune Response

et al. 2022

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Both strong innate and adaptive immune responses are an important component of protection against intraerythrocytic protozoan parasites. Resistance to bovine babesiosis is associated with interferon (IFN)-γ mediated responses. CD4+ T cells and macrophages have been identified as major effector cells mediating the clearance of pathogens. Previously, the apical membrane antigen 1 (AMA-1) was found to significantly induce the immune response inhibiting B. bovis merozoite growth and invasion. However, a detailed characterization of both humoral and cellular immune responses against the structure of B. bovis AMA-1 (BbAMA-1) has not yet been established. Herein, the present study aimed to express the recombinant BbAMA-1 domain I+II protein [rBbAMA-1(I/II)], which is the most predominant immune response region, and to characterize its immune response. As a result, cattle vaccinated with BbAMA-1(I/II) significantly developed high titters of total immunoglobulin (Ig) G antibodies and a high ratio of IgG2/IgG1 when compared to control groups. Interestingly, the BbAMA-1(I/II)-based formulations produced in our study could elicit CD4+ T cells and CD8+ T cells producing IFN-γ and tumor necrosis factor (TNF)-α. Collectively, the results indicate that immunization of cattle with BbAMA-1(I/II) could induce strong Th1 cell responses. In support of this, we observed the up-regulation of Th1 cytokine mRNA transcripts, including IFN-γ, TNF-α, Interleukin (IL)-2 and IL-12, in contrast to down regulation of IL-4, IL-6 and IL-10, which would be indicative of a Th2 cytokine response. Moreover, the up-regulation of inducible nitric oxide synthase (iNOS) was observed. In conclusion, this is the first report on the in-depth immunological characterization of the response to BbAMA-1. According to our results, BbAMA-1 is recognized as a potential candidate vaccine against B. bovis infection. As evidenced by the Th1 cell response, it could potentially provide protective immunity. However, further challenge-exposure with virulent B. bovis strain in immunized cattle would be needed to determine its protective efficacy.

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“…The most characterized AMA‐1 protein is the one codified by Plasmodium falciparum (PfAMA; Peterson et al., 1989). This protein has been extensively studied because, among the few anti‐malarial vaccine candidates under development, it was one of the most promising erythrocyte stage candidates (Latitha et al., 2008). PfAMA‐1 is a protein of 622 residues and a molecular weight of 83 KDa and three major domains defined by eight disulphide bonds (Escalante et al., 2001; Deans et al., 1988; Hodder et al., 1996).…”

Section: Introductionmentioning

confidence: 99%

Characterization of the Apical Membrane Antigen-1 in Italian Strains of Babesia bigemina

Torina

Agnone

Sireci

et al. 2010

Transboundary and Emerging Diseases

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Babesia bigemina is a parasite endemic in different parts of the world, including Europe and the Americas. One of the few genes characterized in this species codifies for the Apical Membrane Antigen 1 (AMA-1), a trans-membrane antigen recently identified. In this research, we characterized the ama-1 gene from three Italian B. bigemina strains, two B. bigemina strains obtained from Ragusa, Sicily (ITA1 and ITA3) and a third one obtained from Benevento, Campania (ITA2). Italian sequences were compared with those of the Australian strain obtained from the Sanger Institute web site and to strains from different parts of the world. The results obtained confirmed that this newly described ama-1 gene is highly conserved among Italian and foreign strains which has implications for vaccine development.

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Immunogenicity of a recombinant malaria vaccine candidate, domain I+II of AMA-1 ectodomain, from Indian P. falciparum alleles

Cited by 6 publications

References 47 publications

Mixed allele malaria vaccines: Host protection and within-host selection

Mixed allele malaria vaccines: Host protection and within-host selection

Immunization of Cattle With Recombinant Structural Ectodomains I and II of Babesia bovis Apical Membrane Antigen 1 [BbAMA-1(I/II)] Induces Strong Th1 Immune Response

Characterization of the Apical Membrane Antigen-1 in Italian Strains of Babesia bigemina

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