Antigenic Variation of East/Central/South African and Asian Chikungunya Virus Genotypes in Neutralization by Immune Sera

被引:39
作者
Chua, Chong-Long [1 ]
Sam, I-Ching [1 ]
Merits, Andres [2 ]
Chan, Yoke-Fun [1 ]
机构
[1] Univ Malaya, Dept Med Microbiol, Fac Med, Kuala Lumpur, Malaysia
[2] Univ Tartu, Inst Technol, Tartu, Estonia
关键词
HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE PROTEINS; E2; VACCINE; EXPRESSION; INFECTION; EPITOPE; CELLS; ELECTROSTATICS; SERODIAGNOSIS;
D O I
10.1371/journal.pntd.0004960
中图分类号
R51 [传染病];
学科分类号
100401 ;
摘要
Background Chikungunya virus (CHIKV) is a re-emerging mosquito-borne virus which causes epidemics of fever, severe joint pain and rash. Between 2005 and 2010, the East/Central/South African (ECSA) genotype was responsible for global explosive outbreaks across India, the Indian Ocean and Southeast Asia. From late 2013, Asian genotype CHIKV has caused outbreaks in the Americas. The characteristics of cross-antibody efficacy and epitopes are poorly understood. Methodology/Principal Findings We characterized human immune sera collected during two independent outbreaks in Malaysia of the Asian genotype in 2006 and the ECSA genotype in 2008-2010. Neutralizing capacity was analyzed against representative clinical isolates as well as viruses rescued from infectious clones of ECSA and Asian CHIKV. Using whole virus antigen and recombinant E1 and E2 envelope glycoproteins, we further investigated antibody binding sites, epitopes, and antibody titers. Both ECSA and Asian sera demonstrated stronger neutralizing capacity against the ECSA genotype, which corresponded to strong epitope-antibody interaction. ECSA serum targeted conformational epitope sites in the E1-E2 glycoprotein, and E1-E211K, E2-I2T, E2-H5N, E2-G118S and E2-S194G are key amino acids that enhance cross-neutralizing efficacy. As for Asian serum, the antibodies targeting E2 glycoprotein correlated with neutralizing efficacy, and I2T, H5N, G118S and S194G altered and improved the neutralization profile. Rabbit polyclonal antibody against the N-terminal linear neutralizing epitope from the ECSA sequence has reduced binding capacity and neutralization efficacy against Asian CHIKV. These findings imply that the choice of vaccine strain may impact cross-protection against different genotypes. ' Conclusion/Significance Immune serum from humans infected with CHIKV of either ECSA or Asian genotypes showed differences in binding and neutralization characteristics. These findings have implications for the continued outbreaks of co-circulating CHIKV genotypes and effective design of vaccines and diagnostic serological assays.
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共 59 条
[31]  
Noridah O, 2007, Med J Malaysia, V62, P323
[32]   Serum IgG titres, but not avidity, correlates with neutralizing antibody response after H5N1 vaccination [J].
Pedersen, Gabriel Kristian ;
Hoeschler, Katja ;
Solbak, Sara Marie Oie ;
Bredholt, Geir ;
Pathirana, Rishi Delan ;
Afsar, Aram ;
Breakwell, Lucy ;
Nostbakken, Jane Kristin ;
Raae, Arnt Johan ;
Brokstad, Karl Albert ;
Sjursen, Haakon ;
Zambon, Maria ;
Cox, Rebecca Jane .
VACCINE, 2014, 32 (35) :4550-4557
[33]   UCSF chimera - A visualization system for exploratory research and analysis [J].
Pettersen, EF ;
Goddard, TD ;
Huang, CC ;
Couch, GS ;
Greenblatt, DM ;
Meng, EC ;
Ferrin, TE .
JOURNAL OF COMPUTATIONAL CHEMISTRY, 2004, 25 (13) :1605-1612
[34]   Multiple Immune Factors Are Involved in Controlling Acute and Chronic Chikungunya Virus Infection [J].
Poo, Yee Suan ;
Rudd, Penny A. ;
Gardner, Joy ;
Wilson, Jane A. C. ;
Larcher, Thibaut ;
Colle, Marie-Anne ;
Le, Thuy T. ;
Nakaya, Helder I. ;
Warrilow, David ;
Allcock, Richard ;
Bielefeldt-Ohmann, Helle ;
Schroder, Wayne A. ;
Khromykh, Alexander A. ;
Lopez, Jose A. ;
Suhrbier, Andreas .
PLOS NEGLECTED TROPICAL DISEASES, 2014, 8 (12)
[35]   Re-emergence of chikungunya and o'nyong-nyong viruses: evidence for distinct geographical lineages and distant evolutionary relationships [J].
Powers, AM ;
Brault, AC ;
Tesh, RB ;
Weaver, SC .
JOURNAL OF GENERAL VIROLOGY, 2000, 81 :471-479
[36]   Differential regulation of TLR mediated innate immune response of mouse neuronal cells following infection with novel ECSA genotype of Chikungunya virus with and without E1:A226V mutation [J].
Priya, Raj ;
Dhanwani, R. ;
Patro, I. K. ;
Rao, P. V. L. ;
Parida, M. M. .
INFECTION GENETICS AND EVOLUTION, 2013, 20 :396-406
[37]   Correlation between Dengue-Specific Neutralizing Antibodies and Serum Avidity in Primary and Secondary Dengue Virus 3 Natural Infections in Humans [J].
Puschnik, Andreas ;
Lau, Louis ;
Cromwell, Elizabeth A. ;
Balmaseda, Angel ;
Zompi, Simona ;
Harris, Eva .
PLOS NEGLECTED TROPICAL DISEASES, 2013, 7 (06)
[38]   Immunogenicity, safety, and tolerability of a recombinant measles-virus-based chikungunya vaccine: a randomised, double-blind, placebo-controlled, active-comparator, first-in-man trial [J].
Ramsauer, Katrin ;
Schwameis, Michael ;
Firbas, Christa ;
Muellner, Matthias ;
Putnak, Robert J. ;
Thomas, Stephen J. ;
Despres, Philippe ;
Tauber, Erich ;
Jilma, Bernd ;
Tangy, Frederic .
LANCET INFECTIOUS DISEASES, 2015, 15 (05) :519-527
[39]   I-TASSER: a unified platform for automated protein structure and function prediction [J].
Roy, Ambrish ;
Kucukural, Alper ;
Zhang, Yang .
NATURE PROTOCOLS, 2010, 5 (04) :725-738
[40]   Chikungunya Virus in Macaques, Malaysia [J].
Sam, I-Ching ;
Chua, Chong Long ;
Rovie-Ryan, Jeffrine J. ;
Fu, Jolene Y. L. ;
Tong, Charmaine ;
Sitam, Frankie Thomas ;
Chan, Yoke Fun .
EMERGING INFECTIOUS DISEASES, 2015, 21 (09) :1683-1685