scholarly journals Vaccine Efficacy of Recombinant Plasmodium falciparumMerozoite Surface Protein 1 in Malaria-Naive, -Exposed, and/or -Rechallenged Aotus vociferans Monkeys

2000 ◽  
Vol 68 (3) ◽  
pp. 1418-1427 ◽  
Author(s):  
Andrea F. Egan ◽  
Michael J. Blackman ◽  
David C. Kaslow
Keyword(s):  
Vaccine Efficacy ◽  
Malaria Parasite ◽  
Surface Protein ◽  
Challenge Infection ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
T Cell Epitopes ◽  
Lethal Challenge ◽  
Antibody Titers ◽  
Parasite Challenge

ABSTRACT Protection against a lethal challenge infection of Plasmodium falciparum was elicited in malaria-naive Aotus vociferans monkeys by vaccination with the C terminus 19-kDa protein of the major merozoite surface protein (MSP-119) fused to tetanus toxoid universal T-cell epitopes P30 and P2. Three of four monkeys were protected against a 104-parasite challenge. Four monkeys were challenged with 105 parasites; one self-cured the infection, two were protected against high parasitemia (<2%) but were treated for severe anemia (hematocrit of <25%), and the fourth was not protected. In this model system, anemia appears to be a manifestation of incomplete protection (prolonged low-level parasitemia). Enzyme-linked immunosorbent assay (ELISA) antibody titers correlated with protection. Antibodies from some protected monkeys inhibited secondary processing of MSP-142to MSP-133 and MSP-119. To mimic the repeated reinfections seen in regions where malaria is endemic, a second malaria parasite challenge was administered 4 months later. All P30P2MSP-119-vaccinated monkeys were protected; thus, a single challenge infection may underestimate vaccine efficacy. ELISA antibody titers correlated with protection against a second infection but had decreased compared to the first challenge. As most target populations for asexual blood-stage malaria vaccines will have been exposed to malaria parasites, a malaria parasite-exposed monkey was vaccinated with P30P2MSP-119. This monkey was completely protected, while a malaria parasite-naive P30P2MSP-119-vaccinated monkey self-cured a low-grade parasitemia. Prior malaria parasite infection primed the production of anti-native MSP-119 antibodies, which were boosted by vaccination with recombinant P30P2MSP-119. Preliminary data suggest that immunogenicity studies of vaccines designed for malaria parasite-exposed populations should also be conducted in malaria parasite-exposed subjects.

scholarly journals Immunization of Saimiri sciureus Monkeys with a Recombinant Hybrid Protein Derived from the Plasmodium falciparum Antigen Glutamate-Rich Protein and Merozoite Surface Protein 3 Can Induce Partial Protection with Freund and Montanide ISA720 Adjuvants

2005 ◽  
Vol 12 (2) ◽  
pp. 242-248 ◽  
Author(s):  
Leonardo J. M. Carvalho ◽  
Francisco A. Alves ◽  
Cesare Bianco ◽  
Salma G. Oliveira ◽  
Graziela M. Zanini ◽  
...  
Keyword(s):  
Plasmodium Falciparum ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Challenge Infection ◽  
Saimiri Sciureus ◽  
Enzyme Linked Immunosorbent Assay ◽  
Hybrid Protein ◽  
High Antibody ◽  
Partial Protection ◽  
Antibody Titers

ABSTRACT The immunogenicity and efficacy of a hybrid recombinant protein derived from the N-terminal end of the glutamate-rich protein (GLURP) and the C-terminal portion of the merozoite surface protein 3 (MSP3) of Plasmodium falciparum was evaluated in Saimiri sciureus monkeys. The GLURP/MSP3 hybrid protein, expressed in Lactococcus lactis, was administered in association with alum, Montanide ISA720, or complete or incomplete Freund adjuvant (CFA/IFA) in groups of five animals each. The three formulations were shown to be immunogenic, but the one with alum was shown to be weak compared to the other two, particularly CFA/IFA, which provided very high antibody titers (enzyme-linked immunosorbent assay titers of >3,000,000 and immunofluorescence antibody test titers of 6,400). After a challenge infection with P. falciparum FUP strain, all five monkeys from the GLURP/MSP3-alum group showed a rapid increase in parasitemia, reaching 10% and were treated early. The two monkeys with the highest antibody titers in group GLURP/MSP3-Montanide ISA720 had a delay in the course of parasitemia and were treated late due to a low hematocrit. In the GLURP/MSP3-CFA/IFA group, parasitemia remained below this threshold in four of the five animals and, after it reached a peak, parasitemia started to decrease and monkeys were treated late. When all animals were grouped according to the outcome, a statistically significant association between high antibody titers and partial protection was observed. The challenge infection boosted the antibody titers, and the importance of this event for vaccine efficacy in areas where this parasite is endemic is discussed. In conclusion, these data suggest that GLURP and MSP3 can induce protection against malaria infection if antibodies are induced at properly high titers.

scholarly journals Plasmodium falciparumMSP3 Exists in a Complex on the Merozoite Surface and Generates Antibody Response during Natural Infection

2018 ◽  
Vol 86 (8) ◽  
Author(s):  
Arunaditya Deshmukh ◽  
Bishwanath Kumar Chourasia ◽  
Sonali Mehrotra ◽  
Ikhlaq Hussain Kana ◽  
Gourab Paul ◽  
...  
Keyword(s):  
Malaria Vaccine ◽  
Transmembrane Domain ◽  
Natural Infection ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Mass Spectrometry Analysis ◽  
Enzyme Linked Immunosorbent Assay ◽  
T Cell Epitopes ◽  
Hyperimmune Serum ◽  
Content Type

ABSTRACTPlasmodium falciparummerozoite surface protein 3 (MSP3) is an abundantly expressed secreted merozoite surface protein and a leading malaria vaccine candidate antigen. However, it is unclear how MSP3 is retained on the surface of merozoites without a glycosylphosphatidylinositol (GPI) anchor or a transmembrane domain. In the present study, we identified an MSP3-associated network on thePlasmodiummerozoite surface by immunoprecipitation ofPlasmodiummerozoite lysate using antibody to the N terminus of MSP3 (anti-MSP3N) followed by mass spectrometry analysis. The results suggested the association of MSP3 with other merozoite surface proteins: MSP1, MSP6, MSP7, RAP2, and SERA5. Protein-protein interaction studies by enzyme-linked immunosorbent assay (ELISA) and surface plasmon resonance (SPR) analysis showed that MSP3 complex consists of MSP1, MSP6, and MSP7 proteins. Immunological characterization of MSP3 revealed that MSP3N is strongly recognized by hyperimmune serum from African and Asian populations. Furthermore, we demonstrate that human antibodies, affinity purified against recombinant MSP3N (rMSP3N), promote opsonic phagocytosis of merozoites in cooperation with monocytes. At nonphysiological concentrations, anti-MSP3N antibodies inhibited the growth ofP. falciparum in vitro. Together, the data suggest that MSP3 and especially its N-terminal region containing known B/T cell epitopes are targets of naturally acquired immunity against malaria and also comprise an important candidate for a multisubunit malaria vaccine.

scholarly journals Identification of soluble APO-1 in supernatants of human B- and T-cell lines and increased serum levels in B- and T-cell leukemias

Blood ◽  
1995 ◽  
Vol 85 (6) ◽  
pp. 1562-1569 ◽  
Author(s):  
E Knipping ◽  
KM Debatin ◽  
K Stricker ◽  
B Heilig ◽  
A Eder ◽  
...  
Keyword(s):  
T Cell ◽  
Cell Lines ◽  
Surface Protein ◽  
Serum Levels ◽  
Soluble Form ◽  
Enzyme Linked Immunosorbent Assay ◽  
Low Grade ◽  
Tnf Receptor ◽  
T Cell Lines ◽  
Culture Supernatants

The cell-surface protein APO-1 is a member of the nerve growth factor (NGF)/tumor necrosis factor (TNF) receptor superfamily. APO-1 mediates apoptosis in susceptible cells upon stimulation with the monoclonal antibody anti-APO-1 or upon binding of its natural ligand. Soluble receptors had previously been identified for most members of the NGF/TNF receptor superfamily. Recently, a soluble form of APO-1 (sAPO- 1) was described. We established a sandwich enzyme-linked immunosorbent assay to detect sAPO-1 in culture supernatants of human cell lines and in human sera. sAPO-1 was found in culture supernatants of different human B- and T-cell lines. Molecular weights of sAPO-1 and membrane APO- 1 were similar. In addition, in comparison to healthy donors, sera from patients with different high- and low-grade malignant B- and T-cell leukemias and lymphomas contained increased levels of sAPO-1. These findings may have implications for the growth of leukemias and the diagnostic monitoring of individual patients.

scholarly journals Protective Immune Responses to the 42-Kilodalton (kDa) Region of Plasmodium yoelii Merozoite Surface Protein 1 Are Induced by the C-Terminal 19-kDa Region but Not by the Adjacent 33-kDa Region

2002 ◽  
Vol 70 (2) ◽  
pp. 820-825 ◽  
Author(s):  
Niklas Ahlborg ◽  
Irene T. Ling ◽  
Wendy Howard ◽  
Anthony A. Holder ◽  
Eleanor M. Riley
Keyword(s):  
Gene Segment ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Antibody Responses ◽  
Enzyme Linked Immunosorbent Assay ◽  
Igg Antibody ◽  
Merozoite Surface Protein 1 ◽  
Antibody Titers ◽  
Processing Product

ABSTRACT Vaccination of mice with the 42-kDa region of Plasmodium yoelii merozoite surface protein 1 (MSP142) or its 19-kDa C-terminal processing product (MSP119) can elicit protective antibody responses in mice. To investigate if the 33-kDa N-terminal fragment (MSP133) of MSP142 also induces protection, the gene segment encoding MSP133 was expressed as a glutathione S-transferase (GST) fusion protein. C57BL/6 and BALB/c mice were immunized with GST-MSP133 and subsequently challenged with the lethal P. yoelii YM blood stage parasite. GST-MSP133 failed to induce protection, and all mice developed patent parasitemia at a level similar to that in naive or control (GST-immunized) mice; mice immunized with GST-MSP119 were protected, as has been shown previously. Specific prechallenge immunoglobulin G (IgG) antibody responses to MSP1 were analyzed by enzyme-linked immunosorbent assay and immunofluorescence. Despite being unprotected, several mice immunized with MSP133 had antibody titers (of all IgG subclasses) that were comparable to or higher than those in mice that were protected following immunization with MSP119. The finding that P. yoelii MSP133 elicits strong but nonprotective antibody responses may have implications for the design of vaccines for humans based on Plasmodium falciparum or Plasmodium vivax MSP142.

scholarly journals The Oligomerization Domain of C4-Binding Protein (C4bp) Acts as an Adjuvant, and the Fusion Protein Comprised of the 19-Kilodalton Merozoite Surface Protein 1 Fused with the Murine C4bp Domain Protects Mice against Malaria

2008 ◽  
Vol 76 (8) ◽  
pp. 3817-3823 ◽  
Author(s):  
Solabomi A. Ogun ◽  
Laurence Dumon-Seignovert ◽  
Jean-Baptiste Marchand ◽  
Anthony A. Holder ◽  
Fergal Hill
Keyword(s):  
Fusion Protein ◽  
Binding Protein ◽  
Surface Protein ◽  
Merozoite Surface Protein ◽  
Plasmodium Yoelii ◽  
Protein Antigens ◽  
Merozoite Surface Protein 1 ◽  
Antibody Titers ◽  
Parasite Challenge ◽  
Oligomerization Domain

ABSTRACT Highly purified protein antigens are usually poor immunogens; in practice, adjuvants are needed to obtain satisfactory immune responses. Plasmodium yoelii 19-kDa merozoite surface protein 1 (MSP119) is a weak antigen, but mice vaccinated with this antigen in strong adjuvants can survive an otherwise lethal parasite challenge. Fusion proteins comprising this antigen fused to the oligomerization domain of the murine complement inhibitor C4-binding protein (C4bp) and a series of homologues have been produced. These C4bp domains acted as adjuvants for the fused antigen; the MSP119-murine C4bp fusion protein induced protective immunity in BALB/c mice. Because this fusion protein also induced antibodies against circulating murine C4bp, distantly related C4bp oligomerization domains fused to the same antigen were tested. These homologous domains did not induce antibodies against murine C4bp and, surprisingly, induced higher antibody titers against the antigen than the murine C4bp domain induced. These results demonstrate a new adjuvantlike effect of C4bp oligomerization domains.

scholarly journals Search for Correlates of Protective Immunity Conferred by Anthrax Vaccine

2001 ◽  
Vol 69 (5) ◽  
pp. 2888-2893 ◽  
Author(s):  
Shaul Reuveny ◽  
Moshe D. White ◽  
Yaakov Y. Adar ◽  
Yaron Kafri ◽  
Zeev Altboum ◽  
...  
Keyword(s):  
Antibody Titer ◽  
Neutralizing Antibodies ◽  
Protective Immunity ◽  
Protective Antigen ◽  
Surrogate Marker ◽  
Neutralizing Antibody ◽  
Enzyme Linked Immunosorbent Assay ◽  
Lethal Challenge ◽  
Anthrax Spores ◽  
Antibody Titers

ABSTRACT Vaccination by anthrax protective antigen (PA)-based vaccines requires multiple immunization, underlying the need to develop more efficacious vaccines or alternative vaccination regimens. In spite of the vast use of PA-based vaccines, the definition of a marker for protective immunity is still lacking. Here we describe studies designed to help define such markers. To this end we have immunized guinea pigs by different methods and monitored the immune response and the corresponding extent of protection against a lethal challenge with anthrax spores. Active immunization was performed by a single injection using one of two methods: (i) vaccination with decreasing amounts of PA and (ii) vaccination with constant amounts of PA that had been thermally inactivated for increasing periods. In both studies a direct correlation between survival and neutralizing-antibody titer was found (r 2 = 0.92 and 0.95, respectively). Most significantly, in the two protocols a similar neutralizing-antibody titer range provided 50% protection. Furthermore, in a complementary study involving passive transfer of PA hyperimmune sera to naive animals, a similar correlation between neutralizing-antibody titers and protection was found. In all three immunization studies, neutralization titers of at least 300 were sufficient to confer protection against a dose of 40 50% lethal doses (LD50) of virulent anthrax spores of the Vollum strain. Such consistency in the correlation of protective immunity with anti-PA antibody titers was not observed for antibody titers determined by an enzyme-linked immunosorbent assay. Taken together, these results clearly demonstrate that neutralizing antibodies to PA constitute a major component of the protective immunity against anthrax and suggest that this parameter could be used as a surrogate marker for protection.

scholarly journals Interplay between Protective and Inhibitory Antibodies Dictates the Outcome of Experimentally Disseminated Candidiasis in Recipients of a Candida albicans Vaccine

2002 ◽  
Vol 70 (10) ◽  
pp. 5462-5470 ◽  
Author(s):  
Carla Bromuro ◽  
Antonella Torosantucci ◽  
Paola Chiani ◽  
Stefania Conti ◽  
Luciano Polonelli ◽  
...  
Keyword(s):  
Candida Albicans ◽  
Immune Serum ◽  
Enzyme Linked Immunosorbent Assay ◽  
Fungal Cell ◽  
Lethal Challenge ◽  
Intact Cells ◽  
Passive Protection ◽  
Antibody Titers ◽  
Inhibitory Antibodies ◽  
Y Cells

ABSTRACT Mice immunized with heat-inactivated, whole yeast-form cells (Y cells) of Candida albicans developed intense, specific humoral and cell-mediated immune responses. However, they were modestly protected against a lethal challenge by the fungus, and their sera did not confer passive protection upon nonimmunized animals. Surprisingly, this immune serum conferred an elevated degree of passive protection to normal and SCID mice when preadsorbed on whole C. albicans cells. After adsorption, no antibodies specific to mannoprotein (MP)-rich extracts or secretions were detected by indirect enzyme-linked immunosorbent assay and no serum reaction with the fungal cell surface was seen in immunofluorescence assays. However, this serum had totally preserved the level of other antibodies, in particular those reacting with β-1,3 and β-1,6 glucan (GG). The hypothesis that anti-GG antibodies contributed to the passive protection was suggested by the following circumstantial evidence: (i) mice immunized with C. albicans cells treated with dithiothreitol and protease (YDP cells), which exposed GG on their surfaces and generated anti-GG but not anti-MP antibodies, were substantially protected against a lethal fungus challenge; (ii) the sera, and their immunoglobulin fractions, of mice immunized with YDP cells transferred protection to nonimmune animals; and (iii) this passive protection was substantially abolished by preadsorption on GG but not on intact cells. Overall, our findings demonstrate that some anti-Candida antibodies can block the protective potential of immune serum, a potential to which anti-GG antibodies appear to contribute. Our observations may also help explain why subjects with elevated anti-Candida antibody titers, inclusive of anti-MP and anti-GG antibodies, remain nonetheless susceptible to invasive candidiasis.

scholarly journals Tricomponent Complex Loaded with a Mosquito-Stage Antigen of the Malaria Parasite Induces Potent Transmission-Blocking Immunity

2014 ◽  
Vol 21 (4) ◽  
pp. 561-569 ◽  
Author(s):  
Takeshi Arakawa ◽  
Takafumi Tsuboi ◽  
Jetsumon Sattabongkot ◽  
Kozue Sakao ◽  
Motomi Torii ◽  
...  
Keyword(s):  
Vaccine Efficacy ◽  
Malaria Parasite ◽  
Matrix Protein ◽  
B Lymphocyte ◽  
Large Fraction ◽  
Surface Protein ◽  
Content Type ◽  
Malaria Vaccines ◽  
Binding Avidity ◽  
Immunoglobulin Binding

ABSTRACTThe development of malaria vaccines is challenging, partly because the immunogenicity of recombinant malaria parasite antigens is low. We previously demonstrated that parasite antigens integrated into a tricomponent immunopotentiating complex increase antiparasitic immunity. In this study, the B domains of a group GStreptococcus(SpG) strain andPeptostreptococcus magnus(PpL) were used to evaluate whether vaccine efficacy is influenced by the type of immunoglobulin-binding domain (IBD) in the tricomponent complex. IBDs were fused to a pentameric cartilage oligomeric matrix protein (COMP) to increase the binding avidity of the complexes for their targets. The COMP-IBD fusion proteins generated (COMP-SpG and COMP-PpL and the previously constructed COMP-Z) bound a large fraction of splenic B lymphocytes but not T lymphocytes. These carrier molecules were then loaded with an ookinete surface protein ofPlasmodium vivax, Pvs25, by chemical conjugation. The administration of the tricomponent complexes to mice induced more Pvs25-specific serum IgG than did the unloaded antigen. The PpL complex, which exhibited a broad Ig-binding spectrum, conferred higher vaccine efficacy than did the Z or SpG complexes when evaluated with a membrane feed assay. This study demonstrates that this tricomponent immunopotentiating system, incorporating IBDs as the B-lymphocyte-targeting ligands, is a promising technology for the delivery of malaria vaccines, particularly when combined with an aluminum salt adjuvant.

scholarly journals Anti-HPV16 Antibody Titers Prior to an Incident Cervical HPV16/31 Infection

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1548
Author(s):  
Ana Gradissimo ◽  
Viswanathan Shankar ◽  
Fanua Wiek ◽  
Lauren St. Peter ◽  
Yevgeniy Studentsov ◽  
...  
Keyword(s):  
High Risk ◽  
Hpv Vaccine ◽  
Enzyme Linked Immunosorbent Assay ◽  
Incident Detection ◽  
Antibody Titers ◽  
Circulating Antibodies ◽  
Prospective Association ◽  
Nested Case Control ◽  
Incident Cases

The goal of this study was to investigate the serological titers of circulating antibodies against human papillomavirus (HPV) type 16 (anti-HPV16) prior to the detection of an incident HPV16 or HPV31 infection amongst vaccinated participants. Patients were selected from a prospective post-HPV vaccine longitudinal cohort at Mount Sinai Adolescent Health Center in Manhattan, NY. We performed a nested case–control study of 43 cases with incident detection of cervical HPV16 (n = 26) or HPV31 (n = 17) DNA who had completed the full set of immunizations of the quadrivalent HPV vaccine (4vHPV). Two control individuals whom had received three doses of the vaccine (HPV16/31-negative) were selected per case, matched on age at the first dose of vaccination and follow-up time in the study: a random control, and a high-risk control that was in the upper quartile of a sexual risk behavior score. We conducted an enzyme-linked immunosorbent assay (ELISA) for the detection of immunoglobulin G (IgG) antibodies specific to anti-HPV16 virus-like particles (VLPs). The results suggest that the average log antibody titers were higher among high-risk controls than the HPV16/31 incident cases and the randomly selected controls. We show a prospective association between anti-HPV16 VLP titers and the acquisition of an HPV16/31 incident infection post-receiving three doses of 4vHPV vaccine.

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