scholarly journals Antibodies Against the Plasmodium vivax Apical Membrane Antigen 1 From the Belem Strain Share Common Epitopes Among Other Worldwide Variants

Author(s):  
Ana Caroline Barbosa França ◽  
Kátia Sanches Françoso ◽  
Rodolfo Ferreira Marques ◽  
Gustavo H. G. Trossini ◽  
Renan A. Gomes ◽  
...  

Malaria is a human parasitic disease distributed in many tropical countries and caused by various Plasmodium species. Plasmodium vivax has the largest geographical distribution of the Plasmodium species and is predominant in the Americas, including Brazil. Only a small number of P. vivax vaccine formulations have successfully reached clinical trials relative to their P. falciparum counterparts. One of the candidate antigens for a blood-stage P. vivax vaccine is apical membrane antigen 1 (PvAMA-1). Due to the worldwide distribution of Plasmodium parasites, a high degree of variability has been detected in this antigen sequence, representing a considerable challenge to the development of a universal vaccine against malaria. In this study, we evaluated how PvAMA-1 polymorphisms influence vaccine-derived immune responses in P. vivax malaria. To this end, we expressed 9 recombinant protein representatives of different PvAMA-1 allelic variants in the yeast Pichia pastoris: Belem, Chesson I, Sal-1, Indonesia XIX, SK0814, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS. After protein expression and purification, we evaluated the breadth of the immune responses derived from malaria-exposed individuals from the Amazon region. From 611 serum samples of malaria-exposed individuals, 53.68% of them reacted against the PvAMA-1 Belem through ELISA. Positive samples were further tested against recombinant proteins representing the other PvAMA-1 allelic variants. Whereas Sal-1, Chesson I and SK0814 variants were highly recognized by tested serum samples, Indonesia XIX, TC103, PNG_05_ESP, PNG_62_MU, and PNG_68_MAS were only slightly recognized. Moreover, polyclonal sera derived from C57BL/6 mice immunized with the PvAMA-1 Belem protein predominantly recognized Belem, Sal-1, Chesson I, SK0814, and Indonesia XIX through ELISA. Last, ELISA-based competition assays demonstrated that a previous interaction between anti-Belem polyclonal serum and Sal-1, Chesson I, SK0814, or Indonesia XIX proteins could further inhibit antibody binding to the Belem variant. Our human and mouse data suggest the presence of common epitopes or cross-reactivity between Belem, Sal-1, Chesson I, and SK0814 variants. Although the PvAMA-1 Belem variant induces strain-transcendent antibodies, PvAMA-1 variants from Thailand and Papua New Guinea may need to be included in a universal vaccine formulation to achieve protection against P. vivax malaria.

Vaccine ◽  
2011 ◽  
Vol 29 (43) ◽  
pp. 7491-7504 ◽  
Author(s):  
Sajani Dias ◽  
Maheshika Somarathna ◽  
Aresha Manamperi ◽  
Ananias A. Escalante ◽  
Anusha M. Gunasekera ◽  
...  

2007 ◽  
Vol 366 (5) ◽  
pp. 1523-1537 ◽  
Author(s):  
Sébastien Igonet ◽  
Brigitte Vulliez-Le Normand ◽  
Grazyna Faure ◽  
Marie-Madeleine Riottot ◽  
Clemens H.M. Kocken ◽  
...  

2011 ◽  
Vol 79 (9) ◽  
pp. 3642-3652 ◽  
Author(s):  
Leoneide Érica Maduro Bouillet ◽  
Mariana Oliveira Dias ◽  
Natália Alves Dorigo ◽  
Andrew Douglas Moura ◽  
Bruce Russell ◽  
...  

ABSTRACTApical membrane antigen 1 (AMA-1) is an invasion-relatedPlasmodiumantigen that is expressed during both intracellular and extracellular asexual stages of the parasite's life cycle, making it an ideal target for induction of humoral and cellular immune responses that can protect against malaria. We show here that when it is administered as a recombinant protein (P) in Montanide ISA720 adjuvant, followed by a recombinant human type 5 adenovirus (Ad), intense and long-lastingPlasmodium vivaxAMA-1-specific antibody responses (including both IgG1 and IgG2a), as well as proliferative memory T cell responses, can be detected in immunized mice. Memory T cells displayed both central (CD44hiCD62Lhi) and effector (CD44hiCD62Llo) phenotypes, with the central memory phenotype prevailing (56% of AMA-1-specific proliferating cells). Considering the main traits of the memory immune responses induced against AMA-1, this particular sequence of immunogens (P followed by Ad), but no others (Ad/Ad, Ad/P, or P/P), displayed an optimal synergistic effect. These results give further support to the need for preclinical studies ofP. vivaxvaccine candidate AMA-1 administered in prime/boost protocols that include recombinant proteins and adenoviral vectors.


2003 ◽  
Vol 90 (4) ◽  
pp. 325-329 ◽  
Author(s):  
Joon-Yong Chung ◽  
Eui-Hyun Chun ◽  
Jin-Ho Chun ◽  
Weon-Gyu Kho

1999 ◽  
Vol 67 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Clemens H. M. Kocken ◽  
Martin A. Dubbeld ◽  
Annemarie Van Der Wel ◽  
Jack T. Pronk ◽  
Andrew P. Waters ◽  
...  

ABSTRACT The apical membrane antigen 1 (AMA-1) family is a promising family of malaria blood-stage vaccine candidates that have induced protection in rodent and nonhuman primate models of malaria. Correct conformation of the protein appears to be essential for the induction of parasite-inhibitory responses, and these responses appear to be primarily antibody mediated. Here we describe for the first time high-level secreted expression (over 50 mg/liter) of thePlasmodium vivax AMA-1 (PV66/AMA-1) ectodomain by using the methylotrophic yeast Pichia pastoris. To prevent nonnative glycosylation, a conservatively mutagenized PV66/AMA-1 gene (PV66Δglyc) lacking N-glycosylation sites was also developed. Expression of the PV66Δglyc ectodomain yielded similar levels of a homogeneous product that was nonglycosylated and was readily purified by ion-exchange and gel filtration chromatographies. Recombinant PV66Δglyc43–487 was reactive with conformation-dependent monoclonal antibodies. With the SBAS2 adjuvant,Pichia-expressed PV66Δglyc43–487 was highly immunogenic in five rhesus monkeys, inducing immunoglobulin G enzyme-linked immunosorbent assay titers in excess of 1:200,000. This group of monkeys had a weak trend showing lower cumulative parasite loads following a Plasmodium cynomolgi infection than in the control group.


2006 ◽  
Vol 74 (1) ◽  
pp. 798-801 ◽  
Author(s):  
Thilan Wickramarachchi ◽  
Prasad H. Premaratne ◽  
K. L. R. Lakshman Perera ◽  
Sumith Bandara ◽  
Clemens H. M. Kocken ◽  
...  

ABSTRACT Plasmodium vivax apical membrane antigen 1, an important malaria vaccine candidate, was immunogenic during natural malaria infections in Sri Lanka, where low transmission and unstable malaria conditions prevail. Antibody prevalence increased with exposure in areas where malaria was or was not endemic. A marked isotype switch to cytophilic (immunoglobulin G1 [IgG1]/IgG3) antibodies was evident with increasing exposure exclusively in residents from areas of endemicity.


PLoS ONE ◽  
2011 ◽  
Vol 6 (6) ◽  
pp. e21289 ◽  
Author(s):  
Lilian Lacerda Bueno ◽  
Francisco Pereira Lobo ◽  
Cristiane Guimarães Morais ◽  
Luíza Carvalho Mourão ◽  
Ricardo Andrez Machado de Ávila ◽  
...  

2007 ◽  
Vol 24 (4) ◽  
pp. 939-947 ◽  
Author(s):  
A. M. Gunasekera ◽  
T. Wickramarachchi ◽  
D. E. Neafsey ◽  
I. Ganguli ◽  
L. Perera ◽  
...  

2013 ◽  
Vol 82 (3) ◽  
pp. 1296-1307 ◽  
Author(s):  
Elaine C. Vicentin ◽  
Kátia S. Françoso ◽  
Mariana V. Rocha ◽  
Dmitri Iourtov ◽  
Fernanda L. dos Santos ◽  
...  

ABSTRACTIn a recent vaccine trial performed with African children, immunization with a recombinant protein based onPlasmodium falciparumapical membrane antigen 1 (AMA-1) conferred a significant degree of strain-specific resistance against malaria. To contribute to the efforts of generating a vaccine againstPlasmodium vivaxmalaria, we expressed the ectodomain ofP. vivaxAMA-1 (PvAMA-1) as a secreted soluble protein in the methylotrophic yeastPichia pastoris. Recognized by a high percentage of sera from individuals infected byP. vivax, this recombinant protein was found to have maintained its antigenicity. The immunogenicity of this protein was evaluated in mice using immunization protocols that included homologous and heterologous prime-boost strategies with plasmid DNA and recombinant protein. We used the following formulations containing different adjuvants: aluminum salts (Alum),Bordetella pertussismonophosphoryl lipid A (MPLA), flagellin FliC fromSalmonella entericaserovar Typhimurium, saponin Quil A, or incomplete Freund's adjuvant (IFA). The formulations containing the adjuvants Quil A or IFA elicited the highest IgG antibody titers. Significant antibody titers were also obtained using a formulation developed for human use containing MPLA or Alum plus MPLA. Recombinant PvAMA-1 produced under “conditions of good laboratory practice” provided a good yield, high purity, low endotoxin levels, and no microbial contaminants and reproduced the experimental immunizations. Most relevant for vaccine development was the fact that immunization with PvAMA-1 elicited invasion-inhibitory antibodies against different Asian isolates ofP. vivax. Our results show that AMA-1 expressed inP. pastorisis a promising antigen for use in future preclinical and clinical studies.


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