Attenuation of coxsackievirus B3 by VP2 mutation and its application as a vaccine against virus-induced myocarditis and pancreatitis.
Coxsackievirus B3 (CVB3) is a common agent of viral myocarditis, a major cause of sudden cardiac death, and ultimately dilated cardiomyopathy. However, there is no vaccine in clinical use. In this study, we identified the conserved amino acid sequences in the C-terminal region of the VP2 of the coxsackievirus B group and some echoviruses. The mutant virus, YYFF, with phenylalanines substituted for two tyrosines in these conserved sequences was highly attenuated in vivo and could induce a high neutralizing antibody titer and a cytotoxic T-lymphocyte response against CVB3. Thereby, mutant-virus-immunized mice showed a 100% survival rate and protection against inflammation of the heart and pancreas after lethal dose challenge. Thus, this mutant virus is a good candidate for an attenuated CVB3 vaccine.
Park
Jung-Hyun
JH
Department of Biotechnology, The Catholic University of Korea, Bucheon 420-743, Republic of Korea.
Kim
Dae-Sun
DS
Cho
Young-Joo
YJ
Kim
Yeon-Jung
YJ
Jeong
Soo-Young
SY
Lee
Seung-Min
SM
Cho
Seong-Joo
SJ
Yun
Cheol-Won
CW
Jo
Inho
I
Nam
Jae-Hwan
JH
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D000914:Antibodies, Viral / Q000097:blood / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics / Q000276:immunology*; D017124:Conserved Sequence; D003384:Coxsackievirus Infections / Q000150:complications / Q000517:prevention & control*; D004770:Enterovirus / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009154:Mutation; D009205:Myocarditis / Q000209:etiology / Q000517:prevention & control* / Q000821:virology; D009500:Neutralization Tests; D010195:Pancreatitis / Q000209:etiology / Q000517:prevention & control* / Q000821:virology; D017434:Protein Structure, Tertiary; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014613:Vaccines, Attenuated / Q000276:immunology; D014765:Viral Vaccines / Q000276:immunology*
D000914:Antibodies, Viral; D036022:Capsid Proteins; D014613:Vaccines, Attenuated; D014765:Viral Vaccines