scholarly journals Pathways for Potentiation of Immunogenicity during Adjuvant-Assisted Immunizations with Plasmodium falciparumMajor Merozoite Surface Protein 1

1998 ◽  
Vol 66 (11) ◽  
pp. 5329-5336 ◽  
Author(s):  
George S. N. Hui ◽  
Caryn N. Hashimoto
Keyword(s):  
Immune Responses ◽  
Animal Species ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Mouse Strains ◽  
Vaccine Adjuvants ◽  
Merozoite Surface Protein 1 ◽  
Ifn Γ ◽  
Animal Hosts

Vaccine adjuvants exert critical and unique influences on the quality of immune responses induced during active immunizations. We investigated the mechanisms of action of immunological adjuvants in terms of their requirements for cytokine-mediated pathways for adjuvanticity. Antibody responses potentiated by several adjuvants to a Plasmodium falciparum MSP1-19 (C-terminal 19-kDa processing fragment of MSP1) vaccine were studied in gamma interferon (IFN-γ) or interleukin (IL-4) knockout mice. The levels of anti-MSP1-19 antibodies and the induction of Th1- and Th2-type antibodies were analyzed. Results revealed a spectrum of requirements for cytokine-mediated pathways in the potentiation of immunogenicity, and such requirements were influenced by interactions among individual components of the adjuvant formulations. One adjuvant strictly depended on IFN-γ to induce appreciable levels of anti-MSP1-19 antibodies, while some formulations required IFN-γ only for the induction of Th1-type antibodies. Other formulations induced exclusively Th2-type antibodies and were not affected by IFN-γ knockout. There were three patterns of requirements for IL-4 by various adjuvants in the induction of Th2-type anti-MSP1-19 antibodies. Moreover, the induction of Th1-type anti-MSP1-19 antibodies by adjuvants showed two distinct patterns of regulation by IL-4. The utilization of an IL-4 regulated pathway(s) for the induction of Th2-type antibodies by the same adjuvant differed between mouse strains, suggesting that animal species variability in responses to vaccine adjuvants may be due, at least in part, to differences in the utilization of immune system pathways by an adjuvant among animal hosts.

scholarly journals Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment of Plasmodium ovale imported from Africa into China

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Qinwen Xu ◽  
Sihong Liu ◽  
Kokouvi Kassegne ◽  
Bo Yang ◽  
Jiachen Lu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Immune Responses ◽  
Expression System ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Enzyme Linked Immunosorbent Assay ◽  
High Avidity ◽  
Plasmodium Ovale ◽  
Merozoite Surface Protein 1 ◽  
Proliferation Assays

Abstract Background Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa region of MSP1 has long been considered one of the major candidate antigens for a malaria blood-stage vaccine against Plasmodium falciparum. However, there is limited information on the C-terminal 19-kDa region of Plasmodium ovale MSP1 (PoMSP119). This study aims to analyze the genetic diversity and immunogenicity of PoMSP119. Methods A total of 37 clinical Plasmodium ovale isolates including Plasmodium ovale curtisi and Plasmodium ovale wallikeri imported from Africa into China and collected during the period 2012–2016 were used. Genomic DNA was used to amplify P. ovale curtisi (poc) msp119 (pocmsp119) and P. ovale wallikeri (pow) msp119 (powmsp119) genes by polymerase chain reaction. The genetic diversity of pomsp119 was analyzed using the GeneDoc version 6 programs. Recombinant PoMSP119 (rPoMSP119)-glutathione S-transferase (GST) proteins were expressed in an Escherichia coli expression system and analyzed by western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assay. In addition, antigen-specific T cell responses were assessed by lymphocyte proliferation assays. A total of 49 serum samples from healthy individuals and individuals infected with P. ovale were used for the evaluation of natural immune responses by using protein microarrays. Results Sequences of pomsp119 were found to be thoroughly conserved in all the clinical isolates. rPoMSP119 proteins were efficiently expressed and purified as ~ 37-kDa proteins. High antibody responses in mice immunized with rPoMSP119-GST were observed. rPoMSP119-GST induced high avidity indexes, with an average of 92.57% and 85.32% for rPocMSP119 and rPowMSP119, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found in the splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for the detection of natural immune responses in patients infected with P. ovale were 89.96% and 75%, respectively. Conclusions This study revealed highly conserved gene sequences of pomsp119. In addition, naturally acquired humoral immune responses against rPoMSP1 were observed in P. ovale infections, and high immunogenicity of rPoMSP119 in mice was also identified. These instructive findings should encourage further testing of PoMSP119 for rational vaccine design. Graphical abstract

scholarly journals A Reduced Risk of Infection with Plasmodium vivax and Clinical Protection against Malaria Are Associated with Antibodies against the N Terminus but Not the C Terminus of Merozoite Surface Protein 1

2006 ◽  
Vol 74 (5) ◽  
pp. 2726-2733 ◽  
Author(s):  
Paulo Afonso Nogueira ◽  
Fabiana Piovesan Alves ◽  
Carmen Fernandez-Becerra ◽  
Oliver Pein ◽  
Neida Rodrigues Santos ◽  
...  
Keyword(s):  
Immune Responses ◽  
Plasmodium Vivax ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Risk Of Infection ◽  
Merozoite Surface Protein 1 ◽  
C Terminus ◽  
N Terminus ◽  
Clinical Protection ◽  
Reduced Risk

ABSTRACT Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. The occurrence of clinical protection in P. vivax malaria in Brazil was first reported among residents of the riverine community of Portuchuelo, in Rondônia, western Amazon. We thus analyzed immune sera from this same human population to determine if naturally acquired humoral immune responses against the merozoite surface protein 1 of P. vivax, PvMSP1, could be associated with reduced risk of infection and/or clinical protection. Our results demonstrated that this association could be established with anti-PvMSP1 antibodies predominantly of the immunoglobulin G3 subclass directed against the N terminus but not against the C terminus, in spite of the latter being more immunogenic and capable of natural boosting. This is the first report of a prospective study of P. vivax malaria demonstrating an association of reduced risk of infection and clinical protection with antibodies against an antigen of this parasite.

scholarly journals Genetic diversity and immunogenicity of the merozoite surface protein 1 C-terminal 19-kDa fragment (MSP119) of Plasmodium ovale imported from Africa to China

2021 ◽  
Author(s):  
Qinwen Xu ◽  
Sihong Liu ◽  
Kokouvi Kassegne ◽  
Bo Yang ◽  
Jiachen Lu ◽  
...  
Keyword(s):  
Genetic Diversity ◽  
Immune Responses ◽  
Expression System ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
High Avidity ◽  
Natural Immunity ◽  
Plasmodium Ovale ◽  
Merozoite Surface Protein 1 ◽  
Proliferation Assays

Abstract Background Merozoite surface protein 1 (MSP1) plays an essential role in erythrocyte invasion by malaria parasites. The C-terminal 19-kDa of MSP1 has long been considered as one of the major candidate antigens for malaria blood-stage vaccine in Plasmodium falciparum. However, there are limited information on the C-terminal 19-kDa region of Plasmodium ovale merozoite surface protein 1 (PoMSP119). This study, therefore, aims to analyse genetic diversity and immunogenicity of PoMSP119. Methods A total of 37 clinical P. ovale isolates including P. ovale curtisi (Poc) and P. ovale wallikeri (Pow) imported from Africa to China and collected between 2012 and 2016 were used. Genomic DNA were used to amplify pocmsp119 and powmsp119 genes by polymerase chain reaction (PCR). Genetic diversity of pomsp119 was analyzed using the MegAlign and GeneDoc v.6 programs. Recombinant PoMSP119-GST proteins were expressed in an Escherichia coli expression system and analyzed by Western blot. Immune responses in BALB/c mice immunized with rPoMSP119-GST were determined using enzyme-linked immunosorbent assays (ELISA). In addition, antigen-specific T-cell responses were performed by lymphocyte proliferation assays. A total of 49 serum samples from P. ovale infections and healthy people were used to evaluate natural immune responses through protein microarray assays. Results Sequences of pomsp119 were found thoroughly conserved in all clinical isolates. Recombinant PoMSP119 proteins were efficiently expressed and purified as ~ 37 kDa proteins. High antibody responses in immunized mice with rPoMSP119-GST were observed. The rPoMSP119-GST induced high avidity indexes with an average of 92.57% and 85.32% for Poc and Pow, respectively. Cross-reactivity between rPocMSP119 and rPowMSP119 was observed. Cellular immune responses to rPocMSP119 (69.51%) and rPowMSP119 (52.17%) induced in rPocMSP119- and rPowMSP119-immunized mice were found during splenocyte proliferation assays. The sensitivity and specificity of rPoMSP119-GST proteins for natural immune responses detection in patients infected with P. ovale were 89.96% and 75%, respectively. Conclusions This study revealed high conservation in sequences of pomsp119 and high immunogenicity of rPoMSP119. The rPoMSP119 proteins detected humoral immune responses in patients with P. ovale infection. Such informative results advance our understanding of natural immunity to P. ovale infection and contribute to the knowledge base for the development of a PoMSP119-based vaccine.

scholarly journals Allele Specificity of Gamma Interferon Responses to the Carboxyl-Terminal Region of Plasmodium falciparum Merozoite Surface Protein 1 by Kenyan Adults with Naturally Acquired Immunity to Malaria

2010 ◽  
Vol 78 (10) ◽  
pp. 4431-4441 ◽  
Author(s):  
Michele D. Spring ◽  
Kiprotich Chelimo ◽  
Daniel J. Tisch ◽  
Peter Odada Sumba ◽  
Rosemary Rochford ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
T Cell ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Gamma Interferon ◽  
Cell Mediated Immunity ◽  
Multiple Time ◽  
Merozoite Surface Protein 1 ◽  
Ifn Γ ◽  
Over Time

ABSTRACT Cross-sectional seroepidemiological studies of populations naturally exposed to Plasmodium falciparum suggest an association between protection from malaria and circulating antibodies to the carboxyl terminus of merozoite surface protein 1 (MSP1). Questions remain regarding the significance of cell-mediated immunity to MSP1 in conferring protection and inducing immunologic memory. Vaccine constructs have been based on the 42-kDa recombinant MSP1 protein (MSP142), which includes the 19-kDa (MSP119) and 33-kDa (MSP133) fragments containing the major B- and T-cell epitopes, respectively. To evaluate T-cell responses to the MSP133 fragment, two libraries of overlapping 18-mer peptides from the 3D7 and FVO MSP133 regions were used to screen a cohort of asymptomatic Kenyan adults. Gamma interferon (IFN-γ) measured by enzyme-linked immunospot assay (ELISPOT) at multiple time points assessed the magnitude and stability of these responses. The percentage of individuals with IFN-γ responses to single MSP133 peptides ranged from nil to 24%, were clustered among a subset of peptides, and were not consistently recalled over time. In comparison to peptide responses, IFN-γ ELISPOT responses to recombinant MSP142 were more prevalent, more frequently elicited by the 3D7 as opposed to the FVO allele, and more stable over time. The prevailing MSP133 genotype infection was 3D7, with few mixed infections and no sole FVO infections. This study demonstrates that immunity against MSP133 after cumulative natural infections consists of low-magnitude and difficult-to-detect IFN-γ responses. Although immunity against MSP1 alone will not confer protection against malaria, demonstrating a relative and sustained increase in T-cell immunity to MSP1 after vaccination would be a reasonable measurement of vaccine responsiveness.

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