title: An epitope conserved in orthopoxvirus A13 envelope protein is the target of neutralizing and protective antibodies.
abstract: Primary immunization of humans with smallpox vaccine (live vaccinia virus (VACV)) consistently elicits antibody responses to six VACV virion membrane proteins, including A13. However, whether anti-A13 antibody contributes to immune protection against orthopoxviruses was unknown. Here, we isolated a murine monoclonal antibody (mAb) against A13 from a mouse that had been infected with VACV. The anti-A13 mAb bound to recombinant A13 protein with an affinity of 3.4nM and neutralized VACV mature virions. Passive immunization of mice with the anti-A13 mAb protected against intranasal VACV infection. The epitope of the anti-A13 mAb was mapped to a 10-amino acid sequence conserved in all orthopoxviruses, including viriola virus and monkeypox virus, suggesting that anti-A13 antibodies elicited by smallpox vaccine might contribute to immune protection against orthopoxviruses. In addition, our data demonstrates that anti-A13 mAbs are effective for treating orthopoxvirus infection.
authors.affiliation: Department of Microbiology and Immunology, Univ. of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
authors.forename: Chungui
authors.initials: C
authors.lastname: Xu
authors.forename: Xiangzhi
authors.initials: X
authors.lastname: Meng
authors.forename: Bo
authors.initials: B
authors.lastname: Yan
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.forename: Junpeng
authors.initials: J
authors.lastname: Deng
authors.forename: Yan
authors.initials: Y
authors.lastname: Xiang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000276:immunology / Q000302:isolation & purification; D057134:Antibodies, Neutralizing / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D000914:Antibodies, Viral / Q000008:administration & dosage / Q000276:immunology* / Q000302:isolation & purification; D001835:Body Weight; D017124:Conserved Sequence; D004195:Disease Models, Animal; D018604:Epitope Mapping; D018985:Epitopes, B-Lymphocyte / Q000235:genetics / Q000276:immunology*; D007116:Immunization, Passive; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D008993:Monkeypox virus / Q000235:genetics; D009500:Neutralization Tests; D012376:Rodent Diseases / Q000517:prevention & control; D016019:Survival Analysis; D014615:Vaccinia / Q000517:prevention & control; D014616:Vaccinia virus / Q000235:genetics / Q000276:immunology*; D012901:Variola virus / Q000235:genetics; D014759:Viral Envelope Proteins / Q000235:genetics / Q000276:immunology*; D010948:Viral Plaque Assay
chemical_list: D000911:Antibodies, Monoclonal; D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D018985:Epitopes, B-Lymphocyte; D014759:Viral Envelope Proteins