Diagnostic potential of monoclonal antibodies against the capsid protein of chikungunya virus for detection of recent infection

Abstract

Chikungunya fever is self-limiting. However, neurological and hemorrhagic complications have been seen in recent outbreaks. The clinical manifestations of this disease are similar to those of dengue virus infection, indicating the need for differential diagnosis in areas such as India, which are endemic for both viruses. The aim of the present study was to develop monoclonal antibodies (MAbs) against Chikungunya virus (CHIKV) and assess their use in MAb-based IgM capture ELISA (MAC ELISA). The ELISA detects CHIKV-specific IgM antibodies, a marker of recent infection, in a patient's serum. One IgG1 and two IgM isotype hybrids were obtained. All of the subclones derived from the IgG1 hybrid recognized the C protein of CHIKV. The anti-C MAb ClVE4/D9 was the most promising as a detector antibody in MAC ELISA (C-MAb ELISA) yielding higher positive-to-negative (P/N) ratios. When compared with the CHIKV MAC ELISA kit developed by the National Institute of Virology (NIV), Pune (NIV MAC ELISA), the sensitivity of the test was 87.01 % with 100 % specificity. The positive and negative predictive values (PPV and NPV) were 100 % and 94.47 %, respectively. In precision testing, standard deviation (SD) and coefficient of variation (% CV) values of the C-MAb ELISA were within acceptable limits. The C-MAb ELISA detected anti-CHIKV IgM in serum of patients up to five months after the onset of infection, indicating that anti-C MAbs have strong potential for use in MAC ELISA to detect recent CHIKV infection.

Simultaneous detection of IgM antibodies against dengue and chikungunya: Coinfection or cross-reactivity?

“…Cross-reactivity though rare but have been reported with other illness including dengue, although both these viruses belonged to two different families. [16] Suspicion of cross-reactivity was high as approximately 23.4% (18) of positive chikungunya cases had equivocal OD values for dengue serology, and if we combine both true positive dengue along with equivocal dengue numbers, more than half positive chikungunya cases (41, 53.3%) were associated with dengue. On the other hand, coinfection in our study was comparable with 23% and 25.3% from studies done by Mukherjee et al and Kaur et al during same year,.…”

Broad-spectrum monoclonal antibodies against chikungunya virus structural proteins: Promising candidates for antibody-based rapid diagnostic test development

“…However, putative linear B-cell epitopes have been mapped to amino acid residues on CHIKV C protein regions I and III [59]. Several studies have reported on the possible application and diagnostic potential of anti-capsid mAbs [60, 61]. In the present study, anti-CHIKV C protein antibodies were classified into two groups: those showing comparable reactivity among the three CHIKV genotypes (mAbs 24B3 and 26A2) and those with superior reactivity against ECSA compared to CHIKVs of other genotypes (mAbs 32A3, 37C7, and 41G5).…”

Arthritogenic Alphavirus Capsid Protein

“…A further study describes the development of mAb-based IgM capture ELISA (MAC ELISA), which detects CHIKV-specific IgM antibodies. All of the subclones of mAbs derived from the IgG1 hybrid recognized the capsid protein of CHIKV [102].…”