WHO, 2020. Vector-Borne Diseases. Geneva, Switzerland: World Health Organization.
Kularatne SA, Dalugama C, 2022. Dengue infection: Global importance, immunopathology and management. Clin Med (Lond) 22: 9–13.
Dzul-Rosado K, Lugo-Caballero C, Tello-Martin R, López-Avila K, Zavala-Castro J, 2017. Direct evidence of Rickettsia typhi infection in Rhipicephalus sanguineus ticks and their canine hosts. Open Vet J 7: 165–169.
Guzmán-Cornejo C, Rebollo-Hernández A, Herrera-Mares A, Muñoz-Leal S, Castillo-Martínez LD, López-Pérez AM, Cabrera-Garrido M, Oceguera-Figueroa A, 2022. Rickettsia spp. in ticks from a tropical dry forest reserve on Mexico’s Pacific Coast. Ticks Tick Borne Dis 13: 101911.
CDC, 2013. Ensayo de RT-PCR en tiempo real para DENV 1–4 de los CDC, para la detección del virus dengue e identificación de su serotipo. San Juan, Puerto Rico: Centers for Disease Control and Prevention.
Nunes PCG, Lima MRQ, Dos Santos FB, 2022. Molecular diagnosis of dengue. Methods Mol Biol 2409: 157–171.
Lokida D et al., 2020. Comparison of commercial enzyme-linked immunosorbent assay and immunofluorescence assay for diagnosis of acute Rickettsia typhi infections.Vector Borne Zoonotic Dis 20: 93–99.
Zavala-Velazquez J, Ju X-J, Walker DH, 1996. Unrecognized spotted fever group rickettsiosis masquerading as dengue fever in Mexico. Am J Trop Med Hyg 55: 157–159.
Clemen G, Angel J, Montes C, Tovar JR, Osorio L, 2019. Contribución de la prueba rápida NS1 e IgM al diagnóstico de dengue en Colombia en el periodo pre-Zika. Infect 23: 259–265.
Bergamaschi G et al., 2019. Computational analysis of dengue virus envelope protein (E) reveals an epitope with flavivirus immunodiagnostic potential in peptide microarrays. Int J Mol Sci 20: 1921.
Sankar S, Saravanan N, Rajendiran P, Ramamurthy M, Nandagopal B, Sridharan G, 2019. Identification of B- and T-cell epitopes on HtrA protein of Orientia tsutsugamushi.J Cell Biochem 120: 5869–5879.
Trevisan RO et al., 2020. In silico identification of new targets for diagnosis, vaccine, and drug candidates against Trypanosoma cruzi. Dis Markers 2020: 9130719.
Aguilar A, Camacho F, Amin N, Prieto JL, Garay H, Reyes O, Acosta A, 2013. Comparación de la antigenicidad de dos construcciones peptídicas de mimotopos del virus de la hepatitis A mediante suero de ratones inmunizados. VacciMonitor 22: 43–46.
Dzul-Rosado K, Balam-Romero J, Valencia-Pacheco G, Lugo-Caballero C, Arias-León J, Peniche-Lara G, Zavala-Castro J, 2017. Immunogenicity of OmpA and OmpB antigens from Rickettsia rickettsii on mononuclear cells from Rickettsia positive Mexican patients. J Vector Borne Dis 54: 317–327.
Riley SP, Cardwell MM, Chan Y, Pruneau L, Del Piero F, Martinez JJ, 2015. Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice. Pathog Dis 73: ftv101.
Eun-Ju D et al., 2009. Development of recombinant OmpA and OmpB proteins as diagnostic antigens for rickettsial disease. Microbiol Immunol 53: 368–374.
Álvarez-Hernández G, Candia-Plata MC, Bolado-Martínez E, Delgado-de la Mora J, Soto-Guzmán A, López-Soto LF, 2015. Fiebre manchada por Rickettsia rickettsii en las Américas: Un problema crecientsalud pública. Rev Univ Ind Santander Salud 47: 243–259.
Lara-Riegos J et al., 2020. Genetic diversity of HLA system in two populations from Yucatán, Mexico: Mérida and rural Yucatán.Hum Immunol 81: 569–572.
Mishra N et al., 2018. Diagnosis of Zika virus infection by peptide array and enzyme-linked immunosorbent assay. mBio 9: e00095-18.
Raafat N, Blacksell SD, Maude RJ, 2019. A review of dengue diagnostics and implications for surveillance and control. Trans R Soc Trop Med Hyg 113: 653–660.
Martinez-Miranda HA, Balam-Romero JB, Dzul-Rosado KR, 2019. Importancia de las proteínas OmpA y OmpB en el desarrollo de vacunas contra la rickettsiosis.Rev Biomed 30: 73–81.
Cedillo-Barrón L, García-Cordero J, Bustos-Arriaga J, León-Juárez M, Gutiérrez-Castañeda B, 2014. Antibody response to dengue virus. Microbes Infect 16: 711–720.
Sabetian S, Nezafat N, Dorosti H, Zarei M, Ghasemi Y, 2019. Exploring dengue proteome to design an effective epitope-based vaccine against dengue virus.J Biomol Struct Dyn 37: 2546–2563.
Gaspar-Castillo C, Rodríguez MH, Ortiz-Navarrete V, Alpuche-Aranda CM, Martinez-Barnetche J, 2023. Structural and immunological basis of cross-reactivity between dengue and Zika infections: Implications in serosurveillance in endemic regions. Front Microbiol 14: 1107496.
Gong W, Xiong X, Qi Y, Jiao J, Duan C, Wen B, 2014. Identification of novel surface-exposed proteins of Rickettsia rickettsii by affinity purification and proteomics. PLoS One 9: e100253.
Nielsen M, Lund O, Buus S, Lundegaard C, 2010. MHC class II epitope predictive algorithms. Inmunology 130: 319–328.
Meydan C, Otu HH, Sezerman OU, 2013. Prediction of peptides binding to MHC class I and II alleles by temporal motif mining. BMC Bioinformatics 14 (Suppl 2 ):S13.
Owen JA, Punt J, Stranford SA, Jones PP, 2014. KUBY Inmunología, Séptima Edición. New York, NY: McGrawHill.
Aberer JE, 2019. Control de Calidad en pruebas cualitativas aplicado a pruebas serológicas. Acta Bioquím Clín Latinoam 53: 505–510.
Qurollo BA, Stillman BA, Beall MJ, Foster P, Hegarty BC, Breitschwerdt EB, Chandrashekar R, 2021. Comparison of Anaplasma and Ehrlichia species-specific peptide ELISAs with whole organism-based immunofluorescent assays for serologic diagnosis of anaplasmosis and ehrlichiosis in dogs.Am J Vet Res 82: 71–80.
Chikeka I, Matute AJ, Dumler JS, Woods CW, Mayorga O, Reller ME, 2016. Use of peptide-based enzyme-linked immunosorbent assay followed by immunofluorescence assay to document Ehrlichia chaffeensis as a cause of febrile illness in Nicaragua. J Clin Microbiol 54: 1581–1585.
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The socioecological conditions of Mexican regions are conducive to the spread of vector-borne diseases. Although there are established treatment guidelines for dengue and rickettsiosis, diagnosis is complicated. The objective of this work was to identify epitopes of Rickettsia and dengue virus that could be used in serology screening against vector-borne diseases. For this, epitopes with high histocompatibility complex class II binding efficiency of OmpB protein of Rickettsia rickettsii and NS2B protein of dengue virus were identified in silico through a reverse vaccinology strategy. The selected epitopes were grouped into multipeptide sequences that were synthesized and immobilized in a nitrocellulose membrane to evaluate the reactivity sera from patients previously infected with dengue or Rickettsia. The evaluation of the sequences of the NS2B and OmpB proteins was performed with 60 sera previously diagnosed as positive or negative by the respective gold standard techniques. The dot blot technique was used for the antigenic evaluation of the peptides against these serum samples. Dot blot analysis correctly identified 85% of sera positive for rickettsiosis and 75% of sera positive for dengue. Experimental evidence from multipeptide sequences suggests their potential use in the development of diagnostic tests for dengue and rickettsiosis.
Financial support: This study was carried out thanks to the support of the
Disclosures: This study was reviewed and approved by the Research Ethics Committee of the Centro de Investigaciones Regionales “Dr. Hideyo Noguchi” of the Universidad Autónoma de Yucatán (CEI-17-15). The authors assert that all procedures contributing to this work comply with the ethical standards of the relevant national and institutional committees on human experimentation and with the Helsinki Declaration of 1975 as revised in 2008.
Authors’ contributions: C. A. Peña-Bates, C. I. Lugo-Caballero, and K. R. Dzul-Rosado conceptualized the study. C. A. Peña-Bates, C. I. Lugo-Caballero, H. R. Noh-Pech, and K. R. Dzul-Rosado contributed to methodology. C. A. Peña-Bates, C. I. Lugo-Caballero, H. R. Noh-Pech, and K. R. Dzul-Rosado contributed to investigation. C. A. Peña-Bates wrote the original draft. C. I. Lugo-Caballero and K. R. Dzul-Rosado contributed supervision. C. I. Lugo-Caballero, O. Omodior, F. I. Puerto-Manzano, and K. R. Dzul-Rosado reviewed and edited the writing. C. I. Lugo-Caballero, N. Pavía-Ruz, F. I. Puerto-Manzano, and K. R. Dzul-Rosado provided resources.
Current contact information: Carlos A. Peña-Bates, Cesar I. Lugo-Caballero, Norma Pavía-Ruz, Henry R. Noh-Pech, Fernando I. Puerto-Manzano, and Karla R. Dzul-Rosado, Centro de Investigaciones Regionales “Dr. Hideyo Noguchi,” Universidad Autónoma de Yucatán, Mérida, México, E-mails: krlox.peba@hotmail.com, cesar.lugo@correo.uady.mx, pruz@correo.uady.mx, henry.noh@correo.uady.mx, pmanzano@correo.uady.mx, and karla.dzul@correo.uady.mx. Oghenekaro Omodior, Health Affairs Institute, West Virginia University, Charleston, WV, E-mail: omodior@hsc.wvu.edu.
WHO, 2020. Vector-Borne Diseases. Geneva, Switzerland: World Health Organization.
Kularatne SA, Dalugama C, 2022. Dengue infection: Global importance, immunopathology and management. Clin Med (Lond) 22: 9–13.
Dzul-Rosado K, Lugo-Caballero C, Tello-Martin R, López-Avila K, Zavala-Castro J, 2017. Direct evidence of Rickettsia typhi infection in Rhipicephalus sanguineus ticks and their canine hosts. Open Vet J 7: 165–169.
Guzmán-Cornejo C, Rebollo-Hernández A, Herrera-Mares A, Muñoz-Leal S, Castillo-Martínez LD, López-Pérez AM, Cabrera-Garrido M, Oceguera-Figueroa A, 2022. Rickettsia spp. in ticks from a tropical dry forest reserve on Mexico’s Pacific Coast. Ticks Tick Borne Dis 13: 101911.
CDC, 2013. Ensayo de RT-PCR en tiempo real para DENV 1–4 de los CDC, para la detección del virus dengue e identificación de su serotipo. San Juan, Puerto Rico: Centers for Disease Control and Prevention.
Nunes PCG, Lima MRQ, Dos Santos FB, 2022. Molecular diagnosis of dengue. Methods Mol Biol 2409: 157–171.
Lokida D et al., 2020. Comparison of commercial enzyme-linked immunosorbent assay and immunofluorescence assay for diagnosis of acute Rickettsia typhi infections.Vector Borne Zoonotic Dis 20: 93–99.
Zavala-Velazquez J, Ju X-J, Walker DH, 1996. Unrecognized spotted fever group rickettsiosis masquerading as dengue fever in Mexico. Am J Trop Med Hyg 55: 157–159.
Clemen G, Angel J, Montes C, Tovar JR, Osorio L, 2019. Contribución de la prueba rápida NS1 e IgM al diagnóstico de dengue en Colombia en el periodo pre-Zika. Infect 23: 259–265.
Bergamaschi G et al., 2019. Computational analysis of dengue virus envelope protein (E) reveals an epitope with flavivirus immunodiagnostic potential in peptide microarrays. Int J Mol Sci 20: 1921.
Sankar S, Saravanan N, Rajendiran P, Ramamurthy M, Nandagopal B, Sridharan G, 2019. Identification of B- and T-cell epitopes on HtrA protein of Orientia tsutsugamushi.J Cell Biochem 120: 5869–5879.
Trevisan RO et al., 2020. In silico identification of new targets for diagnosis, vaccine, and drug candidates against Trypanosoma cruzi. Dis Markers 2020: 9130719.
Aguilar A, Camacho F, Amin N, Prieto JL, Garay H, Reyes O, Acosta A, 2013. Comparación de la antigenicidad de dos construcciones peptídicas de mimotopos del virus de la hepatitis A mediante suero de ratones inmunizados. VacciMonitor 22: 43–46.
Dzul-Rosado K, Balam-Romero J, Valencia-Pacheco G, Lugo-Caballero C, Arias-León J, Peniche-Lara G, Zavala-Castro J, 2017. Immunogenicity of OmpA and OmpB antigens from Rickettsia rickettsii on mononuclear cells from Rickettsia positive Mexican patients. J Vector Borne Dis 54: 317–327.
Riley SP, Cardwell MM, Chan Y, Pruneau L, Del Piero F, Martinez JJ, 2015. Failure of a heterologous recombinant Sca5/OmpB protein-based vaccine to elicit effective protective immunity against Rickettsia rickettsii infections in C3H/HeN mice. Pathog Dis 73: ftv101.
Eun-Ju D et al., 2009. Development of recombinant OmpA and OmpB proteins as diagnostic antigens for rickettsial disease. Microbiol Immunol 53: 368–374.
Álvarez-Hernández G, Candia-Plata MC, Bolado-Martínez E, Delgado-de la Mora J, Soto-Guzmán A, López-Soto LF, 2015. Fiebre manchada por Rickettsia rickettsii en las Américas: Un problema crecientsalud pública. Rev Univ Ind Santander Salud 47: 243–259.
Lara-Riegos J et al., 2020. Genetic diversity of HLA system in two populations from Yucatán, Mexico: Mérida and rural Yucatán.Hum Immunol 81: 569–572.
Mishra N et al., 2018. Diagnosis of Zika virus infection by peptide array and enzyme-linked immunosorbent assay. mBio 9: e00095-18.
Raafat N, Blacksell SD, Maude RJ, 2019. A review of dengue diagnostics and implications for surveillance and control. Trans R Soc Trop Med Hyg 113: 653–660.
Martinez-Miranda HA, Balam-Romero JB, Dzul-Rosado KR, 2019. Importancia de las proteínas OmpA y OmpB en el desarrollo de vacunas contra la rickettsiosis.Rev Biomed 30: 73–81.
Cedillo-Barrón L, García-Cordero J, Bustos-Arriaga J, León-Juárez M, Gutiérrez-Castañeda B, 2014. Antibody response to dengue virus. Microbes Infect 16: 711–720.
Sabetian S, Nezafat N, Dorosti H, Zarei M, Ghasemi Y, 2019. Exploring dengue proteome to design an effective epitope-based vaccine against dengue virus.J Biomol Struct Dyn 37: 2546–2563.
Gaspar-Castillo C, Rodríguez MH, Ortiz-Navarrete V, Alpuche-Aranda CM, Martinez-Barnetche J, 2023. Structural and immunological basis of cross-reactivity between dengue and Zika infections: Implications in serosurveillance in endemic regions. Front Microbiol 14: 1107496.
Gong W, Xiong X, Qi Y, Jiao J, Duan C, Wen B, 2014. Identification of novel surface-exposed proteins of Rickettsia rickettsii by affinity purification and proteomics. PLoS One 9: e100253.
Nielsen M, Lund O, Buus S, Lundegaard C, 2010. MHC class II epitope predictive algorithms. Inmunology 130: 319–328.
Meydan C, Otu HH, Sezerman OU, 2013. Prediction of peptides binding to MHC class I and II alleles by temporal motif mining. BMC Bioinformatics 14 (Suppl 2 ):S13.
Owen JA, Punt J, Stranford SA, Jones PP, 2014. KUBY Inmunología, Séptima Edición. New York, NY: McGrawHill.
Aberer JE, 2019. Control de Calidad en pruebas cualitativas aplicado a pruebas serológicas. Acta Bioquím Clín Latinoam 53: 505–510.
Qurollo BA, Stillman BA, Beall MJ, Foster P, Hegarty BC, Breitschwerdt EB, Chandrashekar R, 2021. Comparison of Anaplasma and Ehrlichia species-specific peptide ELISAs with whole organism-based immunofluorescent assays for serologic diagnosis of anaplasmosis and ehrlichiosis in dogs.Am J Vet Res 82: 71–80.
Chikeka I, Matute AJ, Dumler JS, Woods CW, Mayorga O, Reller ME, 2016. Use of peptide-based enzyme-linked immunosorbent assay followed by immunofluorescence assay to document Ehrlichia chaffeensis as a cause of febrile illness in Nicaragua. J Clin Microbiol 54: 1581–1585.
Past two years | Past Year | Past 30 Days | |
---|---|---|---|
Abstract Views | 49363 | 49363 | 13761 |
Full Text Views | 75 | 75 | 9 |
PDF Downloads | 25 | 25 | 0 |