Pathologic and immunologic characteristics of coxsackievirus A16 infection in rhesus macaques

Highlights

• CV-A16 infection does not induce an effective immune response.

• The inactivated CV-A16 vaccine induces neutralizing antibodies and a T-cell response.

• The inactivated CV-A16 vaccine fails to protect against viral challenge.

• Pre-conventional dendritic cells play a role in this abnormal immune response.

Abstract

Coxsackievirus A16 (CV-A16) causes human hand, foot and mouth disease, but its pathogenesis is unclear. In rhesus macaques, CV-A16 infection causes characteristic vesicles in the oral mucosa and limbs as well as viremia and positive viral loads in the tissues, suggesting that these animals reflect the pathologic process of the infection. An immunologic analysis indicated a defective immune response, which included undetectable neutralizing antibodies and IFN-γ-specific memory T-cells in macaques infected with CV-A16. Furthermore, existing neutralizing antibodies in macaques immunized with the inactivated vaccine were surprisingly unable to protect against a viral challenge despite the presence of a positive T-cell memory response against viral antigens. The virus was capable of infecting pre-conventional dendritic cells and replicating within them, which may correlate with the immunological characteristics observed in the animals.