Abstract
Coxsackievirus A16 (CA16) is one of the major causative agents of hand, foot, and mouth disease worldwide. The non-neutralizing antibody response that targets CA16 VP1 remains poorly elucidated. In the present study, antibody responses against CA16 VP1 in Shanghai blood donors and Shanxi individuals were analyzed by ELISA and inhibitory ELISA using five CA16 VP1 antigens: VP11-297, VP141-297, VP11-60, VP145-58 and VP161-297. The correlation coefficients for most of the reactions against each of the five antigens and the inhibition of the anti-CA16 VP1 antibody response produced by the various antigens were higher in Shanghai blood donors compared to those in Shanxi individuals. VP11-297 and VP141-297 strongly inhibited the anti-CA16 VP1 response in serum samples from both populations, while VP145-58 and VP161-297 intermediately and weakly inhibited the anti-CA16 VP1 response, respectively, in only Shanghai group. A specific type of inhibition (anti-CA16 VP1 was completely inhibited by both VP11-60 and VP141-297) characterized by high neutralizing antibody titers was identified and accounted for 71.4% of the strongly reactive samples from the Shanghai group. These results indicate that the Shanghai blood donors exhibited a consistent and specific antibody response, while the Shanxi individuals showed an inconsistent and non-specific antibody response. These findings may improve the understanding of host humoral immunity against CA16 and help to identify an effective approach for seroepidemiological surveillance and specific diagnosis of CA16 infection based on normal and competitive ELISA.
Highlights
Hand, foot, and mouth disease (HFMD) is a common infectious illness that usually affects children, those less than 5 years old [1,2,3]
We proposed the hypothesis that the nonneutralizing antibody response that targets Coxsackievirus A16 (CA16) VP1 should involve both the antibody response that is elicited by infection with CA16 and the cross-reactive antibody response elicited by infection with CA16-related enteroviruses such as enterovirus 71 (EV71), CA6 and CA10
The size of each recombinant protein was in agreement with its expected molecular weight. pET21b-VP11-297, pET32aVP141-297 and pET32a-VP161-297 were located in inclusion bodies and could be solubilized in 8 M urea and conveniently purified under denaturing conditions. pET32a-VP11-60 and pET32a-VP145-58 were found in the soluble fractions of bacterial lysates
Summary
Foot, and mouth disease (HFMD) is a common infectious illness that usually affects children, those less than 5 years old [1,2,3]. Since the first case was reported in 1969, HFMD has continued to spread globally and is a continuing threat to public health [4,5,6]. Since 2008, a dramatic increase in the prevalence of HFMD has been reported in mainland China [1, 11,12,13]. Coxsackievirus A16 (CA16) and enterovirus 71 (EV71) are the major etiological agents of HFMD. The isolation of an increasing number of enteroviruses (EV, a genus in the Picornaviridae family) has allowed their phylogenic classification into 12 species, namely, enterovirus A, B, C, D, E, F, G, H and J (EV A–J) and rhinovirus A, B and C. In addition to CA2-8, A10, A12, A14 and EV71, CA16 has been classified as an EV A species based on its genome sequence [14, 15]
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