Evaluation of the safety and immunogenicity of Plasmodium falciparum apical membrane antigen 1, merozoite surface protein 1 or RTS,S vaccines with adjuvant system AS02A administered alone or concurrently in rhesus monkeys

Vaccine ◽  
2009 ◽  
Vol 28 (2) ◽  
pp. 452-462 ◽  
Author(s):  
S. Pichyangkul ◽  
P. Tongtawe ◽  
U. Kum-Arb ◽  
K. Yongvanitchit ◽  
M. Gettayacamin ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Rhesus Monkeys ◽  
Apical Membrane ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Surface Protein 1 ◽  
Apical Membrane Antigen ◽  
Adjuvant System

scholarly journals Prediction of Merozoite Surface Protein 1 and Apical Membrane Antigen 1 Vaccine Efficacies against Plasmodium chabaudi Malaria Based on Prechallenge Antibody Responses

2008 ◽  
Vol 16 (3) ◽  
pp. 293-302 ◽  
Author(s):  
Michelle M. Lynch ◽  
Amy Cernetich-Ott ◽  
William P. Weidanz ◽  
James M. Burns
Keyword(s):  
Apical Membrane ◽  
Protective Efficacy ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasmodium Chabaudi ◽  
Apical Membrane Antigen 1 ◽  
Merozoite Surface Protein 1 ◽  
Apical Membrane Antigen

ABSTRACT For the development of blood-stage malaria vaccines, there is a clear need to establish in vitro measures of the antibody-mediated and the cell-mediated immune responses that correlate with protection. In this study, we focused on establishing correlates of antibody-mediated immunity induced by immunization with apical membrane antigen 1 (AMA1) and merozoite surface protein 142 (MSP142) subunit vaccines. To do so, we exploited the Plasmodium chabaudi rodent model, with which we can immunize animals with both protective and nonprotective vaccine formulations and allow the parasitemia in the challenged animals to peak. Vaccine formulations were varied with regard to the antigen dose, the antigen conformation, and the adjuvant used. Prechallenge antibody responses were evaluated by enzyme-linked immunosorbent assay and were tested for a correlation with protection against nonlethal P. chabaudi malaria, as measured by a reduction in the peak level of parasitemia. The analysis showed that neither the isotype profile nor the avidity of vaccine-induced antibodies correlated with protective efficacy. However, high titers of antibodies directed against conformation-independent epitopes were associated with poor vaccine performance and may limit the effectiveness of protective antibodies that recognize conformation-dependent epitopes. We were able to predict the efficacies of the P. chabaudi AMA1 (PcAMA1) and P. chabaudi MSP142 (PcMSP142) vaccines only when the prechallenge antibody titers to both refolded and reduced/alkylated antigens were considered in combination. The relative importance of these two measures of vaccine-induced responses as predictors of protection differed somewhat for the PcAMA1 and the PcMSP142 vaccines, a finding confirmed in our final immunization and challenge study. A similar approach to the evaluation of vaccine-induced antibody responses may be useful during clinical trials of Plasmodium falciparum AMA1 and MSP142 vaccines.

scholarly journals Vaccination of Monkeys with Recombinant Plasmodium falciparum Apical Membrane Antigen 1 Confers Protection against Blood-Stage Malaria

2002 ◽  
Vol 70 (12) ◽  
pp. 6961-6967 ◽  
Author(s):  
Anthony W. Stowers ◽  
Michael C. Kennedy ◽  
Brian P. Keegan ◽  
Allan Saul ◽  
Carole A. Long ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Malaria Vaccine ◽  
Vaccine Development ◽  
Apical Membrane ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Lethal Challenge ◽  
Apical Membrane Antigen 1 ◽  
Apical Membrane Antigen

ABSTRACT A major challenge facing malaria vaccine development programs is identifying efficacious combinations of antigens. To date, merozoite surface protein 1 (MSP1) is regarded as the leading asexual vaccine candidate. Apical membrane antigen 1 (AMA1) has been identified as another leading candidate for an asexual malaria vaccine, but without any direct in vivo evidence that a recombinant form of Plasmodium falciparum AMA1 would have efficacy. We evaluated the efficacy of a form of P. falciparum AMA1, produced in Pichia pastoris, by vaccinating Aotus vociferans monkeys and then challenging them with P. falciparum parasites. Significant protection from this otherwise lethal challenge with P. falciparum was observed. Five of six animals had delayed patency; two of these remained subpatent for the course of the infection, and two controlled parasite growth at <0.75% of red blood cells parasitized. The protection induced by AMA1 was superior to that obtained with a form of MSP1 used in the same trial. The protection induced by a combination vaccine of AMA1 and MSP1 was not superior to the protection obtained with AMA1 alone, although the immunity generated appeared to operate against both vaccine components.

scholarly journals Human Leukocyte Antigen Class II Alleles Influence Levels of Antibodies to the Plasmodium falciparum Asexual-Stage Apical Membrane Antigen 1 but Not to Merozoite Surface Antigen 2 and Merozoite Surface Protein 1

2004 ◽  
Vol 72 (5) ◽  
pp. 2762-2771 ◽  
Author(s):  
Armead H. Johnson ◽  
Rose G. F. Leke ◽  
Nancy R. Mendell ◽  
Dewon Shon ◽  
Young Ju Suh ◽  
...  
Keyword(s):  
Apical Membrane ◽  
Surface Protein ◽  
Human Leukocyte ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Apical Membrane Antigen 1 ◽  
Leukocyte Antigen ◽  
Merozoite Surface Protein 1 ◽  
Merozoite Surface Antigen ◽  
Antibody Levels

ABSTRACT The apical membrane antigen 1 (AMA1), merozoite surface antigen 2 (MSA2), and merozoite surface protein 1 (MSP1) are asexual-stage proteins currently being evaluated for inclusion in a vaccine for Plasmodium falciparum. Accordingly, it is important to understand factors that control antibody responses to these antigens. Antibody levels in plasma from residents of Etoa, Cameroon, between the ages of 5 and 70 years, were determined using recombinant AMA1, MSA2, and the N-terminal region of MSP1 (MSP1-190L). In addition, antibody responses to four variants of the C-terminal region of MSP1 (MSP119) were assessed. Results showed that all individuals produced antibodies to AMA1, MSA2, and MSP1-190L; however, a proportion of individuals never produced antibodies to the MSP119 variants, although the percentage of nonresponders decreased with age. The influence of age and human leukocyte antigen (HLA)-DRB1/DQB1 alleles on antibody levels was evaluated using two-way analysis of variance. Age was correlated with levels of antibodies to AMA1 and MSP119 but not with levels of antibodies to MSA2 and MSP1-190L. No association was found between a single HLA allele and levels of antibodies to MSA2, MSP1-190L, or any of the MSP119 variants. However, individuals positive for DRB1*1201 had higher levels of antibodies to the variant of recombinant AMA1 tested than did individuals of all other HLA types. Since the effect was seen across all age groups, HLA influenced the level but not the rate of antibody acquisition. This association for AMA1, combined with the previously reported association between HLA class II alleles and levels of antibodies to rhoptry-associated protein 1 (RAP1) and RAP2, indicates that HLA influences the levels of antibodies to three of the five vaccine candidate antigens that we have evaluated.

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