Abstract
Chikungunya virus (CHIKV) infection is endemic in many different countries. CHIKV outbreaks are emerging in new areas and re-emerging in previously exposed geographical regions, thus making it a significant public health concern. CHIKV infections are often clinically inapparent, especially in children, which poses a challenge to testing and evaluating any vaccine. During CHIKV infection, CHIKV-specific antibodies are produced, and some of these antibodies can neutralize viruses released from infected cells before they can enter uninfected cells. In this study, we evaluated IgG binding and neutralizing antibody responses in paired serum samples from CHIKV-infected children and those with other febrile illness, using a recombinant truncated E2 protein and whole CHIKV particles as test antigens. Antibody detection using the truncated E2 protein showed a significant overlap between CHIKV-infected subjects and those with other febrile illnesses. This overlap was greater when binding antibody titers were determined using fixed CHIKV particles as the test antigen. Acute- and convalescent-phase sera collected from children after CHIKV infection showed significant differences in their neutralizing capacity. The neutralizing and binding antibody response showed a significant positive correlation. We detected IgG antibodies in most cases during the acute phase of infection. This was observed at two different geographical locations, one of which is not considered highly endemic. Conventional wisdom would suggest this to be a marker of re-infection (secondary infection). However, dissenting opinions have been voiced in other viral diseases (such as Ebola) where studies have detected IgG in acute illness. In the absence of any significant body of work documenting secondary CHIKV infections, we believe further work is needed to understand the early IgG response that we observed.
Similar content being viewed by others
References
Silva LA, Dermody TS (2017) Chikungunya virus: epidemiology, replication, disease mechanisms, and prospective intervention strategies. J Clin Investig 127(3):737–749
Staples JE, Breiman RF, Powers AM (2009) Chikungunya fever: an epidemiological review of a re-emerging infectious disease. Clin Infect Dis 49(6):942–948
Lumsden WH (1955) An epidemic of virus disease in Southern Province, Tanganyika Territory, in 1952–53. II. General description and epidemiology. Trans. R. Soc. Trop. Med. Hyg. 49:33–57
Paquet C, Quatresous I, Solet JL, Sissoko D, Renault P, Pierre V, Cordel H, Lassalle C, Thiria J, Zeller H, Schuffnecker I (2006) Chikungunya outbreak in Reunion: epidemiology and surveillance, 2005 to early January 2006. Euro Surveill. 11(2):E060202.3. https://doi.org/10.2807/esw.11.05.02891-en
Centers for Disease Control and Prevention, National Center for Emerging and Zoonotic Infectious Diseases, Division of Vector-Borne Diseases. Chikungunya virus in the United States. Chikungunya Virus website. https://www.cdc.gov/chikungunya/geo/united-states.html. Accessed 9 March 2020
Solignat M, Gay B, Higgs S, Briant L, Devaux C (2009) Replication cycle of chikungunya: a re-emerging arbovirus. Virology 393:183–197
Thiboutot MM, Kannan S, Kawalekar OU, Shedlock DJ, Khan AS, Sarangan G, Srikanth P, Weiner DB, Muthumani K (2010) Chikungunya: a potentially emerging epidemic? PLoS Negl Trop Dis 4:e623
Tang BL (2012) The cell biology of Chikungunya virus infection. Cell Microbiol. 14(9):1354–1363. https://doi.org/10.1111/j.1462-5822.2012.01825
Jaffar-Bandjee MC, Ramful D, Gauzere BA, Hoarau JJ, Krejbich-Trotot P, Robin S, Ribera A, Selambarom J, Gasque P (2010) Emergence and clinical insights into the pathology of Chikungunya virus infection. Expert Rev Anti Infect Ther 8:987–996
Couderc T, Chrétien F, Schilte C, Disson O, Brigitte M, Guivel-Benhassine F, Touret Y, Barau G, Cayet N, Schuffenecker I, Desprès P, Arenzana-Seisdedos F, Michault A, Albert ML, Lecuit M (2008) A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease. PLoS Pathog 4:e29. https://doi.org/10.1371/journal.ppat.0040029
Aoyama I, Uno K, Yumisashi T, Takasaki T, Lim C-K, Kurane I, Kase T, Takahashi K (2010) A case of chikungunya fever imported from India to Japan, follow-up of specific IgM and IgG antibodies over a 6-month period. Jpn J Infect Dis 63:65–66
Ray P, Ratagiri VH, Kabra SK, Lodha R, Sharma S, Sharma BS, Kalaivani M, Wig N (2012) Chikungunya infection in India: results of a prospective hospital based multi-centric study. PLoS One 7:e30025. https://doi.org/10.1371/journal.pone.0030025
Raghavendhar BS, Ray P, Ratagiri VH, Sharma BS, Kabra SK, Lodha R (2016) Evaluation of chikungunya virus infection in children from India during 2009–2010: a cross sectional observational study. J. Med. Virol 88:923–930. https://doi.org/10.1002/jmv.24433
Kam YW, Lum FM, Teo TH, Lee WWL, Simarmata D, Harjanto S, Chua CL, Chan YF, Wee JK, Chow A, Lin RTP, Leo YS, Le Grand R, Sam IC, Tong JC, Roques P, Wiesmüller KH, Rénia L, Rötzschke O, Ng LFP (2012) Early neutralizing IgG response to Chikungunya virus in infected patients targets a dominant linear epitope on the E2 glycoprotein. EMBO Mol Med 4:330–343
Lee CY, Kam YW, Fric J, Malleret B, Koh EGL, Prakash C, Huang W, Lee WWL, Lin C, Lin RTP, Renia L, Wang CI, Ng LFP, Warter L (2011) Chikungunya virus neutralization antigens and direct cell-to-cell transmission are revealed by human antibody-escape mutants. PLoS Pathog 7:e1002390
Murin CD, Wilson IA, Ward AB (2019) Antibody responses to viral infections: a structural perspective across three different enveloped viruses. Nat Microbiol 4(5):734–747. https://doi.org/10.1038/s41564-019-0392
Sourisseau M, Schilte C, Casartelli N, Trouillet C, Guivel BF, Rudnicka D, Sol-Foulon N, Le Roux K, Prevost M-C, Fsihi H, Frenkiel MP, Blanchet F, Afonso PV, Ceccaldi PE, Ozden S, Gessain A, Schuffenecker I, Verhasselt B, Zamborlini A, Saïb A, Rey FA, Arenzana SF, Desprès P, Michault A, Albert ML, Schwartz O (2007) Characterization of reemerging chikungunya virus. PLoS Pathog 3:e89. https://doi.org/10.1371/journal.ppat.0030089
Kam YW, Lee WWL, Simarmata D, Harjanto S, Teng TS, Tolou H, Chow A, Lin RTP, Leo YS, Rénia L, Ng LFP (2012) Longitudinal analysis of the human antibody response to Chikungunya virus infection: implications for serodiagnosis and vaccine development. J Virol 86:13005–13015. https://doi.org/10.1128/JVI.01780-12
Verma A, Chandele A, Nayak K, Kaja MK, Arulandu A, Lodha R, Ray P (2016) High yield expression and purification of Chikungunya virus E2 recombinant protein and its evaluation for serodiagnosis. J Virol Methods 235:73–79. https://doi.org/10.1016/j.jviromet.2016.05.003
Frey A, Di Canzio J, Zurakowski D (1998) A statistically defined endpoint titer determination method for immunoassays. J Immunol Methods 221:35–41
Rosenstock S, Jorgensen T, Andersen L, Bonnevie O (2000) Seroconversion and seroreversion in IgG antibodies to Helicobacterpylori: a serology based prospective cohort study. J Epidemiol Community Health 54(6):444–450
Nayak K, Jain V, Kaur M, Khan N, Gottimukkala K, Aggarwal C, Sagar R, Gupta S, Rai RC, Dixit K, Islamuddin M, Khan WH, Verma A, Maheshwari D, Chawla YM, Reddy ES, Panda H, Sharma P, Bhatnagar P, Singh P, Raghavendhar BS, Patel AK, Ratageri VH, Chandele A, Ray P, Kaja MK (2020) Antibody response patterns in chikungunya febrile phase predict protection versus progression to chronic arthritis. JCI Insight 5(7):e130509. https://doi.org/10.1172/jci.insight.130509.PMID:32155134
Jain J, Nayak K, Tanwar N, Gaind R, Gupta R, Shastri JS, Bhatnagar RK, Kaja MK, Chandele A, Sunil S (2017) Clinical, serological, and virological analysis of 572 Chikungunya patients from 2010 to 2013 in India. Clin Infect Dis 65:133–140. https://doi.org/10.1093/cid/cix283
Porta J, Jose J, Roehrig JT, Blair CD, Kuhn RJ, Rossmann MG (2014) Locking and blocking the viral landscape of an alphavirus with neutralizing antibodies. J Virol 88:9616–9623. https://doi.org/10.1128/JVI.01286-14
Lum FM, Teo TH, Lee WWL, Kam YW, Renia L, Ng LFP (2013) An essential role of antibodies in the control of Chikungunya virus infection. J Immunol 190:6295–6302. https://doi.org/10.4049/jimmunol.1300304
Chua CL, Sam IC, Merits A, Chan YF (2016) Antigenic variation of East/Central/South African and Asian Chikungunya virus genotypes in neutralization by immune sera. PLoS Negl Trop Dis. https://doi.org/10.1371/journal.pntd.0004960
Cho B, Jeon BY, Kim J, Noh J, Kim J, Park M, Park S (2008) Expression and evaluation of Chikungunya virus E1 and E2 envelope proteins for serodiagnosis of chikungunya virus infection. Yonsei Med J 49:828–835. https://doi.org/10.3349/ymj.2008.49.5.828
Voss JE, Vaney MC, Duquerroy S, Vonrhein C, Girard-Blanc C, Crublet E, Thompson A, Bricogne G, Rey FA (2010) Glycoprotein organization of Chikungunya virus particles revealed by X-ray crystallography. Nature 468:709–712. https://doi.org/10.1038/nature09555
Puschnik A, Lau L, Cromwell EA, Balmaseda A, Zompi S, Harris E (2013) Correlation between dengue-specific neutralizing antibodies and serum avidity in primary and secondary dengue virus 3 natural infections in humans. PLoS Negl Trop Dis. https://doi.org/10.1371/journal.pntd.0002274
Pedersen GK, Höschler K, Oie Solbak SM, Bredholt G, Pathirana RD, Afsar A, Breakwell L, Nøstbakken JK, Raae AJ, Brokstad KA, Sjursen H, Zambon M, Cox RJ (2014) Serum IgG titres, but not avidity, correlates with neutralizing antibody response after H5N1 vaccination. Vaccine 32:4550–4557. https://doi.org/10.1016/j.vaccine.2014.06.009
Acknowledgements
We acknowledge the Department of Biotechnology (DBT), Government of India, for providing financial support to P.R. (grant no.102/IFD/SAN/PR2493/2007 and BT/MB/Indo-US/VAP/06/2013) to carry out this work. We also acknowledge Dr. V.K. Paul, department chair, for providing the facility.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Additional information
Handling Editor: Patricia Aguilar.
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Supplementary Information
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Verma, A., Nayak, K., Chandele, A. et al. Chikungunya-specific IgG and neutralizing antibody responses in natural infection of Chikungunya virus in children from India. Arch Virol 166, 1913–1920 (2021). https://doi.org/10.1007/s00705-021-05049-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00705-021-05049-3