scholarly journals A comparative analysis of memory B cell and antibody responses against Plasmodium falciparum merozoite surface protein 1 in children and adults from Uganda

2021 ◽  
Author(s):  
S Jake Gonzales ◽  
Kathleen N Clarke ◽  
Gayani Batugedara ◽  
Ashley E Braddom ◽  
Rolando Garza ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
B Cells ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Antibody Responses ◽  
Amino Acid Substitutions ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
Specific Igg

Memory B cells (MBCs) and plasma antibodies against Plasmodium falciparum merozoite antigens are important components of the protective immune response against malaria. To gain understanding of how responses against P. falciparum develop in these two arms of the humoral immune system, we evaluated MBC and antibody responses against the most abundant merozoite antigen, merozoite surface protein 1 (MSP1), in individuals from a region in Uganda with high P. falciparum transmission. Our results showed that MSP1-specific B cells in adults with immunological protection against malaria were predominantly IgG+ classical MBCs, while children with incomplete protection mainly harbored IgM+ MSP1-specific classical MBCs. In contrast, anti-MSP1 plasma IgM reactivity was minimal in both children and adults. Instead, both groups showed high plasma IgG reactivity against MSP1 and whole merozoites, with broadening of the response against non-3D7 strains in adults. The antibodies encoded by MSP1-specific IgG+ MBCs carried high levels of amino acid substitutions and recognized relatively conserved epitopes on the highly variable MSP1 protein. Proteomics analysis of MSP119-specific IgG in plasma of an adult revealed a limited repertoire of anti-MSP1 antibodies, most of which were IgG1 or IgG3. Similar to MSP1-specific MBCs, anti-MSP1 IgGs had relatively high levels of amino acid substitutions and their sequences were predominantly found in classical MBCs, not atypical MBCs. Collectively, these results showed evolution of the MSP1-specific humoral immune response with cumulative P. falciparum exposure, with a shift from IgM+ to IgG+ B cell memory, diversification of B cells from germline, and stronger recognition of MSP1 variants by the plasma IgG repertoire.

scholarly journals Plasmodium falciparum Merozoite Surface Protein 1 (MSP-1)-MSP-3 Chimeric Protein: Immunogenicity Determined with Human-Compatible Adjuvants and Induction of Protective Immune Response

2009 ◽  
Vol 78 (2) ◽  
pp. 872-883 ◽  
Author(s):  
Suman Mazumdar ◽  
Paushali Mukherjee ◽  
Syed Shams Yazdani ◽  
S. K. Jain ◽  
Asif Mohmmed ◽  
...  
Keyword(s):  
Immune Response ◽  
Plasmodium Falciparum ◽  
Fusion Protein ◽  
Malaria Vaccine ◽  
Chimeric Protein ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Protective Immune Response ◽  
Merozoite Surface Protein 1

ABSTRACT A chimeric gene, MSP-Fu24 , was constructed by genetically coupling immunodominant, conserved regions of the two leading malaria vaccine candidates, Plasmodium falciparum merozoite surface protein 1 (C-terminal 19-kDa region [PfMSP-119]) and merozoite surface protein 3 (11-kDa conserved region [PfMSP-311]). The recombinant MSP-Fu24 protein was produced in Escherichia coli cells and purified to homogeneity by a two-step purification process with a yield of ∼30 mg/liter. Analyses of conformational properties of MSP-Fu24 using PfMSP-119-specific monoclonal antibody showed that the conformational epitopes of PfMSP-119 that may be critical for the generation of the antiparasitic immune response remained intact in the fusion protein. Recombinant MSP-Fu24 was highly immunogenic in mice and in rabbits when formulated with two different human-compatible adjuvants and induced an immune response against both PfMSP-119 and PfMSP-311. Purified anti-MSP-Fu24 antibodies showed invasion inhibition of P. falciparum 3D7 and FCR parasites, and this effect was found to be dependent on antibodies specific for the PfMSP-119 component. The protective potential of MSP-Fu24 was demonstrated by in vitro parasite growth inhibition using an antibody-dependent cell inhibition (ADCI) assay with anti-MSP-Fu24 antibodies. Overall, the antiparasitic activity was mediated by a combination of growth-inhibitory antibodies generated by both the PfMSP-119 and PfMSP-311 components of the MSP-Fu24 protein. The antiparasitic activities elicited by anti-MSP-Fu24 antibodies were comparable to those elicited by antibodies generated with immunization with a physical mixture of two component antigens, PfMSP-119 and PfMSP-311. The fusion protein induces a protective immune response with human-compatible adjuvants and may form a part of a multicomponent malaria vaccine.

scholarly journals Long-Lasting Protective Immune Response to the 19-Kilodalton Carboxy-Terminal Fragment of Plasmodium yoelii Merozoite Surface Protein 1 in Mice

2007 ◽  
Vol 14 (4) ◽  
pp. 342-347 ◽  
Author(s):  
Pimmada Jeamwattanalert ◽  
Yuvadee Mahakunkijcharoen ◽  
Leera Kittigul ◽  
Pakpimol Mahannop ◽  
Sathit Pichyangkul ◽  
...  
Keyword(s):  
Immune Response ◽  
Antibody Level ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Igg2a Antibody ◽  
Igg1 Antibody ◽  
Merozoite Surface Protein 1 ◽  
Antibody Levels

ABSTRACT Merozoite surface protein 1 (MSP1) is the major protein on the surface of the plasmodial merozoite, and its carboxy terminus, the 19-kDa fragment (MSP119), is highly conserved and effective in induction of a protective immune response against malaria parasite infection in mice and monkeys. However, the duration of the immune response has not been elucidated. As such, we immunized BALB/c mice with a standard four-dose injection of recombinant Plasmodium yoelii MSP119 formulated with Montanide ISA51 and CpG oligodeoxynucleotide (ODN) and monitored the MSP119-specific antibody levels for up to 12 months. The antibody titers persisted constantly over the period of time without significant waning, in contrast to the antibody levels induced by immunization with Freund's adjuvant, where the antibody levels gradually declined to significantly lower levels 12 months after immunization. Investigation of immunoglobulin G (IgG) subclass longevity revealed that only the IgG1 antibody level (Th2 type-driven response) decreased significantly by 6 months, while the IgG2a antibody level (Th1 type-driven response) did not change over the 12 months after immunization, but the boosting effect was seen in the IgG1 antibody responses but not in the IgG2a antibody responses. After challenge infection, all immunized mice survived with negligibly patent parasitemia. These findings suggest that protective immune responses to MSP119 following immunization using oil-based Montanide ISA51 and CpG ODN as an adjuvant are very long-lasting and encourage clinical trials for malaria vaccine development.

scholarly journals N-TerminalPlasmodium vivaxMerozoite Surface Protein-1, a Potential Subunit for Malaria Vivax Vaccine

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Fernanda G. Versiani ◽  
Maria E. Almeida ◽  
Luis A. Mariuba ◽  
Patricia P. Orlandi ◽  
Paulo A. Nogueira
Keyword(s):  
Immune Response ◽  
Protective Immunity ◽  
Malaria Vaccine ◽  
Natural Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Humoral Immune ◽  
Merozoite Surface Protein 1 ◽  
The Western Pacific

The human malaria is widely distributed in the Middle East, Asia, the western Pacific, and Central and South America.Plasmodium vivaxstarted to have the attention of many researchers since it is causing diseases to millions of people and several reports of severe malaria cases have been noticed in the last few years. The lack ofin vitrocultures forP. vivaxrepresents a major delay in developing a functional malaria vaccine. One of the major candidates to antimalarial vaccine is the merozoite surface protein-1 (MSP1), which is expressed abundantly on the merozoite surface and capable of activating the host protective immunity. Studies have shown that MSP-1 possesses highly immunogenic fragments, capable of generating immune response and protection in natural infection in endemic regions. This paper shows humoral immune response to different proteins of PvMSP1 and the statement of N-terminal to be added to the list of potential candidates for malaria vivax vaccine.

scholarly journals Levels of Antibody to Conserved Parts of Plasmodium falciparum Merozoite Surface Protein 1 in Ghanaian Children Are Not Associated with Protection from Clinical Malaria

1999 ◽  
Vol 67 (5) ◽  
pp. 2131-2137 ◽  
Author(s):  
Daniel Dodoo ◽  
Thor G. Theander ◽  
Jorgen A. L. Kurtzhals ◽  
Kojo Koram ◽  
Eleanor Riley ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Clinical Malaria ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Human Antibody ◽  
Merozoite Surface Protein 1 ◽  
Egf Domain ◽  
Antibody Specificities

ABSTRACT The 19-kDa conserved C-terminal part of the Plasmodium falciparum merozoite surface protein 1 (PfMSP119) is a malaria vaccine candidate antigen, and human antibody responses to PfMSP119 have been associated with protection against clinical malaria. In this longitudinal study carried out in an area of stable but seasonal malaria transmission with an estimated parasite inoculation of about 20 infective bites/year, we monitored 266 3- to 15-year-old Ghanaian children clinically and parasitologically over a period of 18 months. Blood samples were collected at the beginning of the study before the major malaria season in April and after the season in November. Using enzyme-linked immunosorbent assay, we measured antibody responses to recombinant gluthathioneS-transferase–PfMSP119 fusion proteins corresponding to the Wellcome and MAD20 allelic variants in these samples. Prevalence of antibodies recognizing the Wellcome 19 construct containing both epidermal growth factor (EGF)-like motifs in Wellcome type PfMSP119 was about 30%. Prevalence of antibodies to constructs containing only the first EGF domain from either Wellcome or MAD20 type PfMSP119 was about 15%, whereas antibodies recognizing a construct containing only the second EGF domain of MAD20 type PfMSP119 was found in only about 4% of the donors. Neither the prevalence nor the levels of any of the antibody specificities varied significantly with season, age, or sex. Significantly, and in contrast to previous reports from other parts of West Africa, we found no evidence of an association between antibody responses to PfMSP119and clinical protection against malaria.

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