Characterization of murine antibody responses to vaccinia virus envelope protein A14 reveals an immunodominant antigen lacking of effective neutralization targets

Virology. 2018 May;518:284-292. doi: 10.1016/j.virol.2018.03.005. Epub 2018 Mar 17.

Abstract

Vaccinia virus (VACV) A14 is a major envelope protein and a dominant antibody target in the smallpox vaccine. However, the role of anti-A14 antibodies in immunity against orthopoxviruses is unclear. Here, we characterized 22 A14 monoclonal antibodies (mAb) from two mice immunized with VACV. Epitope mapping showed that 21 mAbs targeted the C-terminal hydrophilic region, while one mAb recognized the middle region predicted to be across the viral envelope from the C-terminus. However, none of the mAbs bound to virions in studies with electron microscopy. Interestingly, some mAbs showed low VACV neutralization activities in the presence of complement and provided protection to SCID mice challenged with VACV ACAM2000. Our data showed that, although A14 is an immunodominant antigen in smallpox vaccine, its B cell epitopes are either enclosed within the virions or are inaccessible on virion surface. Anti-A14 antibodies, however, could contribute to protection against VACV through a complement-dependent pathway.

Keywords: A14; Antibody; Epitope; Immunization; Neutralization; Smallpox; Vaccinia.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / immunology*
  • Antibodies, Neutralizing / immunology*
  • Antibodies, Viral / immunology*
  • Antibody Formation
  • Antigens, Viral / immunology*
  • Disease Models, Animal
  • Epitope Mapping
  • Immunodominant Epitopes / immunology*
  • Mice, SCID
  • Smallpox Vaccine / immunology*
  • Vaccinia / prevention & control
  • Viral Envelope Proteins / immunology*

Substances

  • A14L protein, Vaccinia virus
  • Antibodies, Monoclonal
  • Antibodies, Neutralizing
  • Antibodies, Viral
  • Antigens, Viral
  • Immunodominant Epitopes
  • Smallpox Vaccine
  • Viral Envelope Proteins