Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus
Abstract
:1. Introduction
2. Results
2.1. Characteristics of the Anti-DENV Complement Fixing Antibody Assay
2.2. Anti-DENV Complement-Fixing Antibody Luminex Assay Comparisons to a Dengue Microneutralization and Dengue Total IgG Binding Assay
2.3. Sensitivity and Specificity of the Complement-Fixing Antibody Assay Compared with the Microneutralization Assay for Each Dengue Virus (DENV) Serotype
2.4. Antibodies Produced after Monospecific DENV Infection Fix Complement against Homologous and Heterologous DENV Serotype Antigens
2.5. Antibodies Produced in Response to Zika Virus Exposure Fix Complement on DENV Structural Proteins
3. Discussion
4. Materials and Methods
4.1. Ethical Statement
4.2. Pre-Vaccination Samples from Human Clinical Trials in Dengue Endemic Areas
4.3. Commercial Samples from Dengue Immune Subjects
4.4. Non-Human Primate Studies
4.5. Coupling of VLPs Expressing Dengue Virus Structural Proteins onto Luminex Magnetic Microspheres
4.6. Anti-DENV Complement-Fixing Antibody Luminex Assay
4.7. Complement C3d Deposition Luminex Assay
4.8. Total Binding IgG ELISA
4.9. Dengue Microneutralization Assay
4.10. Anti-DENV Complement-Fixing Antibody Assay Characteristics
4.11. Homology of Flavivirus Envelope Protein
4.12. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
- Bachal, R.; Alagarasu, K.; Singh, A.; Salunke, A.; Shah, P.; Cecilia, D. Higher levels of dengue-virus-specific IgG and IgA during pre-defervescence associated with primary dengue hemorrhagic fever. Arch. Virol. 2015, 160, 2435–2443. [Google Scholar] [CrossRef] [PubMed]
- Dowd, K.A.; Pierson, T.C. Antibody-mediated neutralization of flaviviruses: A reductionist view. Virology 2011, 411, 306–315. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vázquez, S.; Cabezas, S.; Pérez, A.; Pupo, M.; Ruiz, D.; Calzada, N.; Bernardo, L.; Castro, O.; González, D.; Serrano, T.; et al. Kinetics of antibodies in sera, saliva, and urine samples from adult patients with primary or secondary dengue 3 virus infections. Int. J. Infect. Dis. 2007, 11, 256–262. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Della-Porta, A.J.; Westaway, E.G.; Robbins, S.J.; Bussell, R.H.; Rapp, F. A Multi-Hit Model for the Neutralization of Animal Viruses. J. Gen. Virol. 1978, 38, 1–19. [Google Scholar] [CrossRef]
- Mehlhop, E.; Nelson, S.; Jost, C.A.; Gorlatov, S.; Johnson, S.; Fremont, D.H.; Diamond, M.S.; Pierson, T.C. Complement Protein C1q Reduces the Stoichiometric Threshold for Antibody-Mediated Neutralization of West Nile Virus. Cell Host Microbe 2009, 6, 381–391. [Google Scholar] [CrossRef] [Green Version]
- Yamanaka, A.; Kosugi, S.; Konishi, E. Infection-Enhancing and -Neutralizing Activities of Mouse Monoclonal Antibodies against Dengue Type 2 and 4 Viruses Are Controlled by Complement Levels. J. Virol. 2008, 82, 927–937. [Google Scholar] [CrossRef] [Green Version]
- Carroll, M.C. Complement and humoral immunity. Vaccine 2008, 26, I28–I33. [Google Scholar] [CrossRef] [Green Version]
- Cooper, N.R. The Classical Complement Pathway: Activation and Regulation of the First Complement Component. Adv. Immunol. 1985, 37, 151–216. [Google Scholar] [CrossRef]
- Douradinha, B.; McBurney, S.P.; de Melo, K.M.S.; Smith, A.P.; Krishna, N.K.; Barratt-Boyes, S.M.; Evans, J.D.; Nascimento, E.J.; Marques, E.T. C1q binding to dengue virus decreases levels of infection and inflammatory molecules transcription in THP-1 cells. Virus Res. 2014, 179, 231–234. [Google Scholar] [CrossRef] [Green Version]
- Farrell, K.T. An epidemic of dengue fever in Wewak. Papua New Guin. Med. J. 1978, 21, 191–196. [Google Scholar] [PubMed]
- Monath, T.P.; Craven, R.B.; Muth, D.J.; Trautt, C.J.; Calisher, C.H.; Fitzgerald, S.A. Limitations of the Complement-Fixation Test for Distinguishing Naturally Acquired from Vaccine-Induced Yellow Fever Infection in Flavivirus-Hyperendemic Areas. Am. J. Trop. Med. Hyg. 1980, 29, 624–634. [Google Scholar] [CrossRef]
- Monath, T.P.; Wilson, D.C.; Casals, J. The 1970 yellow fever epidemic in Okwoga District, Benue Plateau State, Nigeria. 3. Serological responses in persons with and without pre-existing heterologous group B immunity. Bull. World Health Organ. 1973, 49, 235–244. [Google Scholar]
- Rice, C.E. The Use of Complement-Fixation Tests in the Study and Diagnosis of Viral Diseases in Man and Animals—A Review, V. The Arborviruses. Can. J. Comp. Med. Vet. Sci. 1960, 24, 352–358. [Google Scholar]
- Sabin, A.B.; Young, I. A Complement Fixation Test for Dengue. Exp. Biol. Med. 1948, 69, 478–480. [Google Scholar] [CrossRef]
- De Paula, S.O.; Fonseca, B. Dengue: A review of the laboratory tests a clinician must know to achieve a correct diagnosis. Braz. J. Infect. Dis. 2004, 8, 390–398. [Google Scholar] [CrossRef] [Green Version]
- Bernet, J.; Mullick, J.; Singh, A.K.; Sahu, A. Viral mimicry of the complement system. J. Biosci. 2003, 28, 249–264. [Google Scholar] [CrossRef]
- Sörman, A.; Zhang, L.; Ding, Z.; Heyman, B. How antibodies use complement to regulate antibody responses. Mol. Immunol. 2014, 61, 79–88. [Google Scholar] [CrossRef]
- Toapanta, F.R.; Ross, T.M. Complement-Mediated Activation of the Adaptive Immune Responses: Role of C3d in Linking the Innate and Adaptive Immunity. Immunol. Res. 2006, 36, 197–210. [Google Scholar] [CrossRef]
- Sirivichayakul, C.; A Barranco-Santana, E.; Rivera, I.E.; Kilbury, J.; Raanan, M.; Borkowski, A.; Papadimitriou, A.; Wallace, D. Long-term Safety and Immunogenicity of a Tetravalent Dengue Vaccine Candidate in Children and Adults: A Randomized, Placebo-Controlled, Phase 2 Study. J. Infect. Dis. 2020, jiaa406. [Google Scholar] [CrossRef]
- Tricou, V.; Sáez-Llorens, X.; Yu, D.; Rivera, L.; Jimeno, J.; Villarreal, A.C.; Dato, E.; de Suman, O.S.; Montenegro, N.; DeAntonio, R.; et al. Safety and immunogenicity of a tetravalent dengue vaccine in children aged 2–17 years: A randomised, placebo-controlled, phase 2 trial. Lancet 2020, 395, 1434–1443. [Google Scholar] [CrossRef]
- Berrar, D.; Flach, P. Caveats and pitfalls of ROC analysis in clinical microarray research (and how to avoid them). Briefings Bioinform. 2012, 13, 83–97. [Google Scholar] [CrossRef] [PubMed]
- Erdei, A.; Isaák, A.; Török, K.; Sándor, N.; Kremlitzka, M.; Prechl, J.; Bajtay, Z. Expression and role of CR1 and CR2 on B and T lymphocytes under physiological and autoimmune conditions. Mol. Immunol. 2009, 46, 2767–2773. [Google Scholar] [CrossRef] [PubMed]
- Dunn, M.D.; Rossi, S.L.; Carter, D.M.; Vogt, M.R.; Mehlhop, E.; Diamond, M.S.; Ross, T.M. Enhancement of anti-DIII antibodies by the C3d derivative P28 results in lower viral titers and augments protection in mice. Virol. J. 2010, 7, 95. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mehlhop, E.; Ansarah-Sobrinho, C.; Johnson, S.; Engle, M.; Fremont, D.H.; Pierson, T.C.; Diamond, M.S. Complement Protein C1q Inhibits Antibody-Dependent Enhancement of Flavivirus Infection in an IgG Subclass-Specific Manner. Cell Host Microbe 2007, 2, 417–426. [Google Scholar] [CrossRef] [Green Version]
- Mehlhop, E.; Fuchs, A.; Engle, M.; Diamond, M.S. Complement modulates pathogenesis and antibody-dependent neutralization of West Nile virus infection through a C5-independent mechanism. Virology 2009, 393, 11–15. [Google Scholar] [CrossRef] [Green Version]
- Mehlhop, E.; Whitby, K.; Oliphant, T.; Marri, A.; Engle, M.; Diamond, M.S. Complement Activation Is Required for Induction of a Protective Antibody Response against West Nile Virus Infection. J. Virol. 2005, 79, 7466–7477. [Google Scholar] [CrossRef] [Green Version]
- Eckels, K.H.; Harrison, V.R.; Hetrick, F.M. Chikungunya virus vaccine prepared by Tween-ether extraction. Appl. Microbiol. 1970, 19, 321–325. [Google Scholar] [CrossRef]
- Hodes, H.L.; Thomas, L.; Peck, J.L. Cause of an Outbreak of Encephalitis Established by Means of Complement-Fixation Tests. Exp. Biol. Med. 1945, 60, 220–225. [Google Scholar] [CrossRef]
- Southam, C.M. Serologic Studies of Encephalitis in Japan I. Hemagglutination-inhibiting, Complement-fixing, and Neutralizing Antibody Following Overt Japanese B Encephalitis. J. Infect. Dis. 1956, 99, 155–162. [Google Scholar] [CrossRef]
- Rowan, L.C. An outbreak of dengue-like fever, North Queensland, 1954; serological findings with the virus neutralization and complement fixation tests. Med J. Aust. 1959, 46, 323–328. [Google Scholar] [CrossRef]
- Smith, C.E.G. A localized outbreak of dengue fever in Kuala Lumpur: Serological aspects. J. Hyg. 1957, 55, 207–223. [Google Scholar] [CrossRef] [Green Version]
- Osorio, J.E.; Velez, I.D.; Thomson, C.; Lopez, L.; Jimenez, A.; Haller, A.A.; Silengo, S.; Scott, J.; Boroughs, K.L.; Stovall, J.L.; et al. Safety and immunogenicity of a recombinant live attenuated tetravalent dengue vaccine (DENVax) in flavivirus-naive healthy adults in Colombia: A randomised, placebo-controlled, phase 1 study. Lancet Infect. Dis. 2014, 14, 830–838. [Google Scholar] [CrossRef] [Green Version]
- Rivera, L.; Biswal, S.; Sáez-Llorens, X.; Reynales, H.; López-Medina, E.; Borja-Tabora, C.; Bravo, L.; Sirivichayakul, C.; Kosalaraksa, P.; Vargas, L.M.; et al. Three years efficacy and safety of Takeda’s dengue vaccine candidate (TAK-003). Clin. Infect. Dis. 2021, ciab864. [Google Scholar] [CrossRef]
- Biswal, S.; Reynales, H.; Saez-Llorens, X.; Lopez, P.; Borja-Tabora, C.; Kosalaraksa, P.; Sirivichayakul, C.; Watanaveeradej, V.; Rivera, L.; Espinoza, F.; et al. Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents. N. Engl. J. Med. 2019, 381, 2009–2019. [Google Scholar] [CrossRef]
- Boudreau, C.; Alter, G. Extra-Neutralizing FcR-Mediated Antibody Functions for a Universal Influenza Vaccine. Front. Immunol. 2019, 10, 440. [Google Scholar] [CrossRef] [Green Version]
- Wahala, W.M.P.B.; De Silva, A.M. The Human Antibody Response to Dengue Virus Infection. Viruses 2011, 3, 2374–2395. [Google Scholar] [CrossRef] [Green Version]
- Venkatachalam, R.; Subramaniyan, V. Homology and conservation of amino acids in E-protein sequences of dengue serotypes. Asian Pac. J. Trop. Dis. 2014, 4, S573–S577. [Google Scholar] [CrossRef]
- Guzman, M.G.; Alvarez, M.; Rodriguez-Roche, R.; Bernardo, L.; Montes, T.; Vazquez, S.; Morier, L.; Alvarez, A.; A Gould, E.; Kourí, G.; et al. Neutralizing Antibodies after Infection with Dengue 1 Virus. Emerg. Infect. Dis. 2007, 13, 282–286. [Google Scholar] [CrossRef]
- Buddhari, D.; Aldstadt, J.; Endy, T.P.; Srikiatkhachorn, A.; Thaisomboonsuk, B.; Klungthong, C.; Nisalak, A.; Khuntirat, B.; Jarman, R.G.; Fernandez, S.; et al. Dengue Virus Neutralizing Antibody Levels Associated with Protection from Infection in Thai Cluster Studies. PLoS Negl. Trop. Dis. 2014, 8, e3230. [Google Scholar] [CrossRef]
- Corbett, K.S.; Katzelnick, L.; Tissera, H.; Amerasinghe, A.; De Silva, A.D.; De Silva, A.M. Preexisting Neutralizing Antibody Responses Distinguish Clinically Inapparent and Apparent Dengue Virus Infections in a Sri Lankan Pediatric Cohort. J. Infect. Dis. 2015, 211, 590–599. [Google Scholar] [CrossRef]
- Gibbons, R.V.; Kalanarooj, S.; Jarman, R.G.; Nisalak, A.; Vaughn, D.W.; Endy, T.P.; Mammen, M.P., Jr.; Srikiatkhachorn, A. Analysis of Repeat Hospital Admissions for Dengue to Estimate the Frequency of Third or Fourth Dengue Infections Resulting in Admissions and Dengue Hemorrhagic Fever, and Serotype Sequences. Am. J. Trop. Med. Hyg. 2007, 77, 910–913. [Google Scholar] [CrossRef] [Green Version]
- Katzelnick, L.C.; Montoya, M.; Gresh, L.; Balmaseda, A.; Harris, E. Neutralizing antibody titers against dengue virus correlate with protection from symptomatic infection in a longitudinal cohort. Proc. Natl. Acad. Sci. USA 2016, 113, 728–733. [Google Scholar] [CrossRef] [Green Version]
- Olkowski, S.; Forshey, B.M.; Morrison, A.C.; Rocha, C.; Vilcarromero, S.; Halsey, E.S.; Kochel, T.J.; Scott, T.W.; Stoddard, S.T. Reduced Risk of Disease During Postsecondary Dengue Virus Infections. J. Infect. Dis. 2013, 208, 1026–1033. [Google Scholar] [CrossRef] [Green Version]
- Mohammed, Y.S.; Grešiková, M.; Adamyová, K.; Ragib, A.H.; El-Dawala, K. Studies on Arboviruses in Egypt: II. Contribution of Arboviruses to the aetiology of undiagnosed fever among children. J. Hyg. 1970, 68, 491–495. [Google Scholar] [CrossRef] [Green Version]
- Crill, W.D.; Hughes, H.R.; DeLorey, M.J.; Chang, G.-J.J. Humoral Immune Responses of Dengue Fever Patients Using Epitope-Specific Serotype-2 Virus-Like Particle Antigens. PLoS ONE 2009, 4, e4991. [Google Scholar] [CrossRef]
- Perez, F.; Llau, A.; Gutierrez, G.; Bezerra, H.; Coelho, G.; Ault, S.; Barbiratto, S.B.; De Resende, M.C.; Cerezo, L.; Kleber, G.L.; et al. The decline of dengue in the Americas in 2017: Discussion of multiple hypotheses. Trop. Med. Int. Health 2019, 24, 442–453. [Google Scholar] [CrossRef]
- Ribeiro, G.S.; Kikuti, M.; Tauro, L.B.; Nascimento, L.C.J.; Cardoso, C.; Campos, G.S.; Ko, A.; Weaver, S.C.; Reis, M.G.; Kitron, U.; et al. Does immunity after Zika virus infection cross-protect against dengue? Lancet Glob. Health 2018, 6, e140–e141. [Google Scholar] [CrossRef] [Green Version]
- Borchering, R.K.; Huang, A.T.; Mier-Y-Teran-Romero, L.; Rojas, D.P.; Rodriguez-Barraquer, I.; Katzelnick, L.C.; Martinez, S.D.; King, G.D.; Cinkovich, S.C.; Lessler, J.; et al. Impacts of Zika emergence in Latin America on endemic dengue transmission. Nat. Commun. 2019, 10, 5730. [Google Scholar] [CrossRef] [Green Version]
- Breitbach, M.E.; Newman, C.M.; Dudley, D.M.; Stewart, L.M.; Aliota, M.T.; Koenig, M.R.; Shepherd, P.M.; Yamamoto, K.; Crooks, C.M.; Young, G.; et al. Primary infection with dengue or Zika virus does not affect the severity of heterologous secondary infection in macaques. PLoS Pathog. 2019, 15, e1007766. [Google Scholar] [CrossRef] [Green Version]
- Pérez-Guzmán, E.X.; Pantoja, P.; Serrano-Collazo, C.; Hassert, M.A.; Ortiz-Rosa, A.; Rodríguez, I.V.; Giavedoni, L.; Hodara, V.; Parodi, L.; Cruz, L.; et al. Time elapsed between Zika and dengue virus infections affects antibody and T cell responses. Nat. Commun. 2019, 10, 4316. [Google Scholar] [CrossRef] [Green Version]
- Katzelnick, L.C.; Narvaez, C.; Arguello, S.; Mercado, B.L.; Collado, D.; Ampie, O.; Elizondo, D.; Miranda, T.; Carillo, F.B.; Mercado, J.C.; et al. Zika virus infection enhances future risk of severe dengue disease. Science 2020, 369, 1123–1128. [Google Scholar] [CrossRef] [PubMed]
- Brito, A.F.; Machado, L.C.; Oidtman, R.J.; Siconelli, M.J.L.; Tran, Q.M.; Fauver, J.R.; Carvalho, R.D.D.O.; Dezordi, F.Z.; Pereira, M.R.; de Castro-Jorge, L.A.; et al. Lying in wait: The resurgence of dengue virus after the Zika epidemic in Brazil. Nat. Commun. 2021, 12, 2619. [Google Scholar] [CrossRef] [PubMed]
- Henderson, A.D.; Aubry, M.; Kama, M.; Vanhomwegen, J.; Teissier, A.; Mariteragi-Helle, T.; Paoaafaite, T.; Teissier, Y.; Manuguerra, J.-C.; Edmunds, J.; et al. Zika seroprevalence declines and neutralizing antibodies wane in adults following outbreaks in French Polynesia and Fiji. eLife 2020, 9, e48460. [Google Scholar] [CrossRef] [PubMed]
- Moreira-Soto, A.; Sampaio, G.D.S.; Pedroso, C.; Postigo-Hidalgo, I.; Berneck, B.S.; Ulbert, S.; Brites, C.; Netto, E.M.; Drexler, J.F. Rapid decline of Zika virus NS1 antigen-specific antibody responses, northeastern Brazil. Virus Genes 2020, 56, 632–637. [Google Scholar] [CrossRef] [PubMed]
- Montoya, M.; Collins, M.; Dejnirattisai, W.; Katzelnick, L.C.; Puerta-Guardo, H.; Jadi, R.; Schildhauer, S.; Supasa, P.; Vasanawathana, S.; Malasit, P.; et al. Longitudinal Analysis of Antibody Cross-neutralization Following Zika Virus and Dengue Virus Infection in Asia and the Americas. J. Infect. Dis. 2018, 218, 536–545. [Google Scholar] [CrossRef] [Green Version]
- Co, M.D.T.; Terajima, M.; Thomas, S.J.; Jarman, R.G.; Rungrojcharoenkit, K.; Fernandez, S.; Yoon, I.-K.; Buddhari, D.; Cruz, J.; Ennis, F.A. Relationship of Preexisting Influenza Hemagglutination Inhibition, Complement-Dependent Lytic, and Antibody-Dependent Cellular Cytotoxicity Antibodies to the Development of Clinical Illness in a Prospective Study of A(H1N1)pdm09 Influenza in Children. Viral Immunol. 2014, 27, 375–382. [Google Scholar] [CrossRef] [Green Version]
- Lofano, G.; Gorman, M.J.; Yousif, A.S.; Yu, W.-H.; Fox, J.M.; Dugast, A.-S.; Ackerman, M.E.; Suscovich, T.J.; Weiner, J.; Barouch, D.; et al. Antigen-specific antibody Fc glycosylation enhances humoral immunity via the recruitment of complement. Sci. Immunol. 2018, 3, eaat7796. [Google Scholar] [CrossRef]
- Rattan, A.; Pawar, S.D.; Nawadkar, R.; Kulkarni, N.; Lal, G.; Mullick, J.; Sahu, A. Synergy between the classical and alternative pathways of complement is essential for conferring effective protection against the pandemic influenza A(H1N1) 2009 virus infection. PLoS Pathog. 2017, 13, e1006248. [Google Scholar] [CrossRef] [Green Version]
- Reiling, L.; Boyle, M.; White, M.T.; Wilson, D.; Feng, G.; Weaver, R.; Opi, D.H.; Persson, K.E.M.; Richards, J.S.; Siba, P.M.; et al. Targets of complement-fixing antibodies in protective immunity against malaria in children. Nat. Commun. 2019, 10, 610. [Google Scholar] [CrossRef] [Green Version]
- Association, W.M. Declaration of Helsinki. Ethical Principles for Medical Research Involving Human Subjects. Available online: https://wwwwmanet/policies-post/wma-declaration-of-helsinki-ethical-principles-for-medical-research-involving-human-subjects/ (accessed on 6 June 2021).
- (ICH) ICfHoTRfPfHU. Guideline for Good Clinical Practice E6(R2). Available online: https://wwwemaeuropaeu/en/ich-e6-r2-good-clinical-practice (accessed on 6 June 2021).
- Young, G.; Bohning, K.J.; Zahralban-Steele, M.; Hather, G.; Tadepalli, S.; Mickey, K.; Godin, C.S.; Sanisetty, S.; Sonnberg, S.; Patel, H.K.; et al. Complete Protection in Macaques Conferred by Purified Inactivated Zika Vaccine: Defining a Correlate of Protection. Sci. Rep. 2020, 10, 3488. [Google Scholar] [CrossRef]
- Michlmayr, D.; Andrade, P.; Nascimento, E.J.M.; Parker, A.; Narvekar, P.; Dean, H.J.; Harris, E. Characterization of the Type-Specific and Cross-Reactive B-Cell Responses Elicited by a Live-Attenuated Tetravalent Dengue Vaccine. J. Infect. Dis. 2021, 223, 247–257. [Google Scholar] [CrossRef]
- Quinn, C.P.; Semenova, V.A.; Elie, C.M.; Romero-Steiner, S.; Greene, C.; Li, H.; Stamey, K.; Steward-Clark, E.; Schmidt, D.S.; Mothershed, E.; et al. Specific, Sensitive, and Quantitative Enzyme-Linked Immunosorbent Assay for Human Immunoglobulin G Antibodies to Anthrax Toxin Protective Antigen. Emerg. Infect. Dis. 2002, 8, 1103–1110. [Google Scholar] [CrossRef]
Study | n | Number of Samples per Age Groups (Years) | |||
---|---|---|---|---|---|
1–5 | 6–11 | 12–20 | >20 | ||
DEN-203 | 37 | 8 | 12 | 10 | 7 |
DEN-204 | 16 | 6 | 8 | 2 | 0 |
Total | 53 | 14 | 20 | 12 | 7 |
Virus | MNT50 Titers | Complement-Fixing Antibody Titers (EU/mL) | ||||
---|---|---|---|---|---|---|
Minimum | Maximum | GeoMean (95% CI) | Minimum | Maximum | GeoMean (95% CI) | |
DENV1 | 5 | 20480 | 19 (10, 35) | 2 | 1915 | 5 (3, 7) |
DENV2 | 5 | 10919 | 20 (10, 40) | 2 | 1565 | 4 (3, 7) |
DENV3 | 5 | 5120 | 15 (9, 26) | 2 | 1564 | 4 (3, 7) |
DENV4 | 5 | 1442 | 12 (7, 20) | 2 | 730 | 4 (3, 6) |
Viruses | Number of Samples | |||||
---|---|---|---|---|---|---|
MNT50 ≥ 10 | Complement ≥ 3 EU/mL | Sensitivity (%) | MNT50 < 10 | Complement < 3 EU/mL | Specificity (%) | |
DENV1 | 17 | 14 | 82% | 36 | 35 | 97% |
DENV2 | 14 | 14 | 100% | 39 | 39 | 100% |
DENV3 | 16 | 13 | 81% | 37 | 37 | 100% |
DENV4 | 12 | 11 | 92% | 41 | 39 | 95% |
DENV1 | DENV2 | DENV3 | DENV4 | ZIKV | JEV | WNV | YFV | TBEV | |
---|---|---|---|---|---|---|---|---|---|
DENV1 | 100 | 69 | 78 | 64 | 59 | 51 | 51 | 43 | 39 |
DENV2 | - | 100 | 69 | 65 | 55 | 48 | 48 | 44 | 38 |
DENV3 | - | - | 100 | 63 | 59 | 49 | 48 | 42 | 38 |
DENV4 | - | - | - | 100 | 57 | 48 | 50 | 40 | 40 |
ZIKV | - | - | - | - | 100 | 54 | 54 | 42 | 40 |
JEV | - | - | - | - | - | 100 | 77 | 45 | 40 |
WNV | - | - | - | - | - | - | 100 | 45 | 42 |
YFV | - | - | - | - | - | - | - | 100 | 41 |
TBEV | - | - | - | - | - | - | - | - | 100 |
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Nascimento, E.J.M.; Norwood, B.; Parker, A.; Braun, R.; Kpamegan, E.; Dean, H.J. Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus. Int. J. Mol. Sci. 2021, 22, 12004. https://doi.org/10.3390/ijms222112004
Nascimento EJM, Norwood B, Parker A, Braun R, Kpamegan E, Dean HJ. Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus. International Journal of Molecular Sciences. 2021; 22(21):12004. https://doi.org/10.3390/ijms222112004
Chicago/Turabian StyleNascimento, Eduardo J. M., Brooke Norwood, Allan Parker, Ralph Braun, Eloi Kpamegan, and Hansi J. Dean. 2021. "Development and Characterization of a Multiplex Assay to Quantify Complement-Fixing Antibodies against Dengue Virus" International Journal of Molecular Sciences 22, no. 21: 12004. https://doi.org/10.3390/ijms222112004