Immune responses of a CV-A16 live attenuated candidate strain and its protective effects in rhesus monkeys.

Coxsackievirus A16 (CV-A16) is a major causative pathogen of hand, foot, and mouth diseases (HFMDs). The licensed HFMD vaccine targets EV-A71 without cross-protection against CV-A16. Thus, an effective CV-A16 vaccine is needed to control HFMD. In this study, the immunogenicity and protective efficacy of a live attenuated CV-A16 candidate, K168-8Ac, were evaluated in a rhesus monkey model. Four passages of this strain (P35, P50, P60, and P70) were administered to monkeys with two doses each via intramuscular (I.M.), intranasal or oral route, and its protective effect was identified by a subsequent viral challenge. The immunised monkeys were clinically asymptomatic, except for slight fever. Weak viremia was observed after immunisation, and two doses of vaccination were found to significantly reduce long term virus shedding. High levels of antibody responses was observed (1:1024-1:2048), along with a significant increase in plasma IL-8. No differences in these indicators between passage groups. However, the I.M. group showed a much stronger humoral immunity. In all the groups, pathological damage was detected mainly in lung tissues although thalamus, spinal cord, lymph nodes and livers were involved. After viral challenge, it was found that two doses of vaccine reduced virus shedding, and the degree of lung damage and the number of organs involved decreased as the passage number of this strain increased. However, these pathological damages were not completely eliminated by vaccination. Overall, a robust immune response and partial protection against CV-A16, triggered by the K168-8Ac strain, were demonstrated. This study provides valuable data for CV-A16 vaccine development.