Immunogenicity and Efficacy in Aotus Monkeys of Four Recombinant Plasmodium falciparum Vaccines in Multiple Adjuvant Formulations Based on the 19-Kilodalton C Terminus of Merozoite Surface Protein 1

ABSTRACT The immunogenicity and protective efficacy of four versions of recombinant C-terminal 19-kDa epidermal growth factor-like region of the major surface protein 1 (rMSP119) of Plasmodium falciparum was studied in Aotus monkeys. Vaccination with each of the four rMSP119 constructs elicited high levels of antibodies to MSP119 but only one construct, the 19-kDa fragment expressed as a secreted fusion protein fromSaccharomyces cerevisiae (yP30P2MSP119), induced a high degree of protective immunity in Aotus nancymai against lethal P. falciparum challenge. Protective formulation required Freund's adjuvant; vaccination with yP30P2MSP119 in six other adjuvants that are suitable for human use induced lower levels of antibody response and no protection. These results emphasize the need to continue the search for an adjuvant that is comparable to Freund's adjuvant in potency and is safe for use in humans.

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Plasmodium falciparum Merozoite Surface Protein 8 Is a Ring-Stage Membrane Protein That Localizes to the Parasitophorous Vacuole of Infected Erythrocytes

Infection and Immunity ◽

10.1128/iai.73.7.3912-3922.2005 ◽

2005 ◽

Vol 73 (7) ◽

pp. 3912-3922 ◽

Cited By ~ 32

Author(s):

Damien R. Drew ◽

Paul R. Sanders ◽

Brendan S. Crabb

Keyword(s):

Plasmodium Falciparum ◽

Parasitophorous Vacuole ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Food Vacuole ◽

Ring Stage ◽

C Terminus ◽

Falciparum Merozoite ◽

Merozoite Antigens ◽

Epidermal Growth

ABSTRACT To date, the following seven glycosylphosphatidylinositol (GPI)-anchored merozoite antigens have been described in Plasmodium falciparum: merozoite-associated surface protein 1 (MSP-1), MSP-2, MSP-4, MSP-5, MSP-8, MSP-10, and the rhoptry-associated membrane antigen. Of these, MSP-1, MSP-8, and MSP-10 possess a double epidermal growth factor (EGF)-like domain at the C terminus, and these modules are considered potential targets of protective immunity. In this study, we found that surprisingly, P. falciparum MSP-8 is transcribed and translated in the ring stage and is absent from the surface of merozoites. MSP-8 is the only GPI-anchored protein known to be expressed at this time. It is synthesized as a mature 80-kDa protein which is rapidly processed to a C-terminal 17-kDa species that contains the double EGF module. As determined by a combination of immunofluorescence and membrane purification approaches, it appears likely that MSP-8 initially localizes to the parasite plasma membrane in the ring stage. Although the C-terminal 17-kDa fragment is present in more mature stages, at these times it is found in the food vacuole. We successfully disrupted the MSP-8 gene in P. falciparum, a process that validated the specificity of the antibodies used in this study and also demonstrated that MSP-8 does not play a role essential to maintenance of the erythrocyte cycle. This finding, together with the observation that MSP-8 is exclusively intracellular, casts doubt over the viability of this antigen as a vaccine. However, it is still possible that MSP-8 is involved in an early parasitophorous vacuole function that is significant for pathogenesis in the human host.

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Production and Preclinical Evaluation of Plasmodium falciparum MSP-119and MSP-311Chimeric Protein, PfMSP-Fu24

Clinical and Vaccine Immunology ◽

10.1128/cvi.00179-14 ◽

2014 ◽

Vol 21 (6) ◽

pp. 886-897 ◽

Cited By ~ 15

Author(s):

Puneet K. Gupta ◽

Paushali Mukherjee ◽

Shikha Dhawan ◽

Alok K. Pandey ◽

Suman Mazumdar ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Malaria Vaccine ◽

Chimeric Protein ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Surface Proteins ◽

Content Type ◽

Freund’S Adjuvant ◽

Freund's Adjuvant

ABSTRACTAPlasmodium falciparumchimeric protein, PfMSP-Fu24, was constructed by genetically coupling immunodominant, conserved regions of two merozoite surface proteins, the 19-kDa region C-terminal region of merozoite surface protein 1 (PfMSP-119) and an 11-kDa conserved region of merozoite surface protein 3 (PfMSP-311), to augment the immunogenicity potential of these blood-stage malaria vaccine candidates. Here we describe an improved, efficient, and scalable process to produce high-quality PfMSP-Fu24. The chimeric protein was produced inEscherichia coliSHuffle T7 ExpresslysYcells that express disulfide isomerase DsbC. A two-step purification process comprising metal affinity followed by cation exchange chromatography was developed, and we were able to obtain PfMSP-Fu24with purity above 99% and with a considerable yield of 23 mg/liter. Immunogenicity of PfMSP-Fu24formulated with several adjuvants, including Adjuplex, Alhydrogel, Adjuphos, Alhydrogel plus glucopyranosyl lipid adjuvant, aqueous (GLA-AF), Adjuphos+GLA-AF, glucopyranosyl lipid adjuvant-stable emulsion (GLA-SE), and Freund's adjuvant, was evaluated. PfMSP-Fu24formulated with GLA-SE and Freund's adjuvant in mice and with Alhydrogel and Freund's adjuvant in rabbits produced high titers of PfMSP-119and PfMSP-311-specific functional antibodies. Some of the adjuvant formulations induced inhibitory antibody responses and inhibitedin vitrogrowth ofP. falciparumparasites in the presence as well as in the absence of human monocytes. These results suggest that PfMSP-Fu24can form a constituent of a multistage malaria vaccine.

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Immunization of Aotus nancymai with recombinant C terminus of Plasmodium falciparum merozoite surface protein 1 in liposomes and alum adjuvant does not induce protection against a challenge infection.

Infection and Immunity ◽

10.1128/iai.64.9.3614-3619.1996 ◽

1996 ◽

Vol 64 (9) ◽

pp. 3614-3619 ◽

Cited By ~ 33

Author(s):

P A Burghaus ◽

B T Wellde ◽

T Hall ◽

R L Richards ◽

A F Egan ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Challenge Infection ◽

Merozoite Surface Protein 1 ◽

C Terminus ◽

Falciparum Merozoite

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Plasmodium falciparum Merozoite Surface Protein 6 Displays Multiple Targets for Naturally Occurring Antibodies That Mediate Monocyte-Dependent Parasite Killing

Infection and Immunity ◽

10.1128/iai.73.2.1235-1238.2005 ◽

2005 ◽

Vol 73 (2) ◽

pp. 1235-1238 ◽

Cited By ~ 27

Author(s):

Subhash Singh ◽

Soe Soe ◽

Christian Roussilhon ◽

Giampietro Corradin ◽

Pierre Druilhe

Keyword(s):

Plasmodium Falciparum ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Naturally Occurring ◽

C Terminus ◽

Sequence Homologies ◽

Merozoite Surface Antigen ◽

Falciparum Merozoite ◽

Erythrocytic Cycle ◽

Naturally Occurring Antibodies

ABSTRACT Plasmodium falciparum MSP6 is a merozoite surface antigen that shows organization and sequence homologies similar to those of MSP3. Within its C-terminus conserved region, it presents some epitopes that are cross-reactive with MSP3 and others that are not, both being targets of naturally occurring antibodies that block the P. falciparum erythrocytic cycle in cooperation with monocytes.

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Immunogenicity and protective efficacy of Escherichia coli expressed Plasmodium falciparum merozoite surface protein-142 using human compatible adjuvants

Vaccine ◽

10.1016/j.vaccine.2005.11.041 ◽

2006 ◽

Vol 24 (12) ◽

pp. 2007-2016 ◽

Cited By ~ 36

Author(s):

Suraksha Sachdeva ◽

Asif Mohmmed ◽

Palakodeti V.N. Dasaradhi ◽

Brendan S. Crabb ◽

Anju Katyal ◽

...

Keyword(s):

Escherichia Coli ◽

Plasmodium Falciparum ◽

Protective Efficacy ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Falciparum Merozoite

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Pam3CSK4 enhances adaptive immune responses to recombinant Mycobacterium bovis bacille Calmette-Guérin expressing Plasmodium falciparum C-terminus merozoite surface protein-1

Asian Pacific Journal of Tropical Biomedicine ◽

10.4103/2221-1691.261742 ◽

2019 ◽

Vol 9 (7) ◽

pp. 271

Author(s):

Rapeah Suppian ◽

MohamedH Abdikarim ◽

MuhammadA Abbas ◽

MunirahN Zakaria ◽

Robaiza Zakaria

Keyword(s):

Plasmodium Falciparum ◽

Immune Responses ◽

Mycobacterium Bovis ◽

Surface Protein ◽

Merozoite Surface Protein ◽

Adaptive Immune Responses ◽

Bacille Calmette Guerin ◽

Adaptive Immune ◽

Merozoite Surface Protein 1 ◽

C Terminus

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Fine Specificity of Serum Antibodies to Plasmodium falciparum Merozoite Surface Protein, PfMSP-119, Predicts Protection from Malaria Infection and High-Density Parasitemia

Infection and Immunity ◽

10.1128/iai.72.3.1557-1567.2004 ◽

2004 ◽

Vol 72 (3) ◽

pp. 1557-1567 ◽

Cited By ~ 75

Author(s):

Brenda A. Okech ◽

Patrick H. Corran ◽

James Todd ◽

Amy Joynson-Hicks ◽

Chairat Uthaipibull ◽

...

Keyword(s):

Plasmodium Falciparum ◽

Surface Protein ◽

Field Studies ◽

Merozoite Surface Protein ◽

High Density ◽

Enzyme Linked Immunosorbent Assay ◽

Fine Specificity ◽

Vaccine Trials ◽

C Terminus ◽

Falciparum Merozoite

ABSTRACT Antibodies to the C terminus of the Plasmodium falciparum merozoite surface protein, PfMSP-119, may inhibit merozoite invasion or block the effects of inhibitory antibodies. Here, using a competition enzyme-linked immunosorbent assay and antibody binding to wild-type and mutated recombinant proteins, we show that there are marked variations between individuals in the fine specificity of naturally acquired anti-MSP-119 antibodies. Furthermore, although neither the prevalence nor the concentration of total anti-MSP-119 antibodies was associated with resistance to malaria in African children, significant associations were observed between antibody fine specificity and subsequent risk of infection and high-density parasitemia during a follow-up period. Thus, the fine specificity of naturally acquired human anti-MSP-119 antibodies is crucial in determining their function. Future field studies, including the evaluation of PfMSP-1 vaccine trials, should include assays that explore antibody fine specificity as well as titer.

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