PMID- 31620136 OWN - NLM STAT- MEDLINE DCOM- 20201022 LR - 20201022 IS - 1664-3224 (Electronic) IS - 1664-3224 (Linking) VI - 10 DP - 2019 TI - Antibody Responses Against Plasmodium vivax TRAP Recombinant and Synthetic Antigens in Naturally Exposed Individuals From the Brazilian Amazon. PG - 2230 LID - 10.3389/fimmu.2019.02230 [doi] LID - 2230 AB - Thrombospondin-related adhesive protein (TRAP) is essential for sporozoite motility and the invasion of mosquitoes' salivary gland and vertebrate's hepatocyte and is, thus, considered a promising pre-erythrocytic vaccine candidate. Despite the existence of a few reports on naturally acquired immune response against Plasmodium vivax TRAP (PvTRAP), it has never been explored so far in the Amazon region, so results are conflicting. Here, we characterized the (IgG and IgG subclass) antibody reactivity against recombinant PvTRAP in a cross-sectional study of 299 individuals exposed to malaria infection in three municipalities (Cruzeiro do Sul, Mancio Lima and Guajara) from the Acre state of the Brazilian Amazon. In addition, the full PvTRAP sequence was screened for B-cell epitopes using in silico and in vitro approaches. Firstly, we confirmed that PvTRAP is naturally immunogenic in the cohort population since 49% of the individuals were IgG-responders to it. The observed immune responses were mainly driven by cytophilic IgG1 over all other sublcasses and the IgG levels that was corelated with age and time of residence in the studied area (p < 0.05). Interestingly, only the levels of specific anti-TRAP IgG3 seemed to be associated with protection, as IgG3 responders presented a significantly higher time elapse since the last malaria episode than those recorded for IgG3 non-responders. Regarding the B-cell epitope mapping, among the 148 responders to PvTRAP, four predicted epitopes were confirmed by recognition of antibodies (PvTRAP(R197-H227); PvTRAP(E237-T258); PvTRAP(P344-G374); and PvTRAP(E439-K454)). Nevertheless, the frequency of responders against these peptides were low and did not show a clear correlation with the antibody response against the corresponding antigen. Moreover, none of the linear confirmed epitopes were located in the binding regions of PvTRAP in respect to the host cell ligand. Collectively, our data confirm the PvTRAP immunogenicity among Amazon inhabitants, while suggesting that the main important B-cell epitopes are not linear. CI - Copyright (c) 2019 Matos, Rodrigues-da-Silva, Soares, Baptista, Souza, Bitencourt-Chaves, Totino, Sanchez-Arcila, Daniel-Ribeiro, Lopez-Camacho, Reyes-Sandoval, Pratt-Riccio and Lima-Junior. FAU - Matos, Ada da Silva AU - Matos ADS AD - Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - Rodrigues-da-Silva, Rodrigo Nunes AU - Rodrigues-da-Silva RN AD - Laboratory of Monoclonal Antibodies Technology, Institute of Immunobiology Technology, Fiocruz, Rio de Janeiro, Brazil. FAU - Soares, Isabela Ferreira AU - Soares IF AD - Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - Baptista, Barbara de Oliveira AU - Baptista BO AD - Laboratory of Malaria Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - de Souza, Rodrigo Medeiros AU - de Souza RM AD - Centre for Health Sciences and Sport, Federal University of Acre (UFAC), Cruzeiro Do Sul, Brazil. FAU - Bitencourt-Chaves, Lana AU - Bitencourt-Chaves L AD - Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - Totino, Paulo Renato Rivas AU - Totino PRR AD - Laboratory of Malaria Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - Sanchez-Arcila, Juan Camilo AU - Sanchez-Arcila JC AD - Viral Immunology Laboratory, Oswaldo Cruz Institute, IOC, Oswaldo Cruz Foundation, Fiocruz, Rio de Janeiro, Brazil. FAU - Daniel-Ribeiro, Claudio Tadeu AU - Daniel-Ribeiro CT AD - Laboratory of Malaria Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - Lopez-Camacho, Cesar AU - Lopez-Camacho C AD - Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom. FAU - Reyes-Sandoval, Arturo AU - Reyes-Sandoval A AD - Nuffield Department of Medicine, The Jenner Institute, University of Oxford, Oxford, United Kingdom. FAU - Pratt-Riccio, Lilian Rose AU - Pratt-Riccio LR AD - Laboratory of Malaria Research, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. FAU - Lima-Junior, Josue da Costa AU - Lima-Junior JDC AD - Laboratory of Immunoparasitology, Oswaldo Cruz Institute, Fiocruz, Rio de Janeiro, Brazil. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20190920 PL - Switzerland TA - Front Immunol JT - Frontiers in immunology JID - 101560960 RN - 0 (Antibodies, Protozoan) RN - 0 (Epitopes, B-Lymphocyte) RN - 0 (Immunoglobulin G) RN - 0 (Malaria Vaccines) RN - 0 (Peptides) RN - 0 (Protozoan Proteins) RN - 0 (Thrombospondins) RN - 0 (Vaccines, Synthetic) SB - IM MH - Adult MH - Amino Acid Sequence MH - Antibodies, Protozoan/immunology MH - Antibody Formation/*immunology MH - Brazil MH - Cohort Studies MH - Cross-Sectional Studies MH - Epitopes, B-Lymphocyte/immunology MH - Female MH - Humans MH - Immunoglobulin G/immunology MH - Malaria Vaccines/immunology MH - Malaria, Vivax/immunology MH - Male MH - Peptides/immunology MH - Plasmodium vivax/*immunology MH - Protozoan Proteins/*immunology MH - Sporozoites/immunology MH - Thrombospondins/immunology MH - Vaccines, Synthetic/*immunology PMC - PMC6763564 OTO - NOTNLM OT - Plasmodium vivax OT - PvTRAP OT - epitope mapping OT - humoral immune response OT - malaria EDAT- 2019/10/18 06:00 MHDA- 2020/10/23 06:00 PMCR- 2019/01/01 CRDT- 2019/10/18 06:00 PHST- 2019/05/23 00:00 [received] PHST- 2019/09/03 00:00 [accepted] PHST- 2019/10/18 06:00 [entrez] PHST- 2019/10/18 06:00 [pubmed] PHST- 2020/10/23 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - 10.3389/fimmu.2019.02230 [doi] PST - epublish SO - Front Immunol. 2019 Sep 20;10:2230. doi: 10.3389/fimmu.2019.02230. eCollection 2019.