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Multicolor Flow Cytometry Analyses of Cellular Immune Response in Rhesus Macaques
Published on: April 22, 2010
Immune responses of a CV-A16 live attenuated candidate strain and its protective effects in rhesus monkeys
Ting Yang1, Tianhong Xie1, Hua Li1
1Institute of Medical Biology, Chinese Academic Medical Sciences and Peking Union Medical College, Kunming, People's Republic of China.
Abstract:
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, a CV-A16 vaccine is needed. 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, and its protective effect was identified. The immunized monkeys were clinically asymptomatic, except for slight fever. Weak viraemia was observed, and two doses of vaccination were found to significantly reduce virus shedding. High levels of antibody responses were observed (1:1024-1:2048), along with a significant increase in plasma IL-8. The I.M. group showed a much stronger humoural immunity. Pathological damage was detected mainly in lung tissues, although thalamus, spinal cord, lymph nodes, and livers were involved. After the 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 increased. 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.
Insights
A new live attenuated Coxsackievirus A16 (CV-A16) vaccine candidate, K168-8Ac, showed promising immunogenicity and partial protection in rhesus monkeys. This development is crucial for combating hand, foot, and mouth diseases (HFMDs) caused by CV-A16.
Area of Science:
- Virology
- Immunology
- Vaccinology
Background:
- Coxsackievirus A16 (CV-A16) is a primary cause of hand, foot, and mouth disease (HFMD).
- Current vaccines target Enterovirus A71 (EV-A71) and lack cross-protection against CV-A16, necessitating a specific CV-A16 vaccine.
Purpose of the Study:
- To evaluate the immunogenicity and protective efficacy of a live attenuated CV-A16 candidate (K168-8Ac) in a rhesus monkey model.
- To assess the impact of different passage levels of the vaccine strain on immune response and protection.
Main Methods:
- Rhesus monkeys were immunized with four passage levels (P35, P50, P60, P70) of the K168-8Ac strain.
- Immunogenicity was assessed through antibody titers and IL-8 levels.
- Protective efficacy was evaluated after viral challenge, monitoring clinical signs, viremia, virus shedding, and pathological damage.
Main Results:
- Vaccinated monkeys showed mild symptoms (slight fever) and reduced viremia.
- Two vaccine doses significantly decreased virus shedding and pathological lung damage.
- High antibody responses (1:1024-1:2048) and increased plasma IL-8 were observed, with intramuscular administration yielding stronger humoral immunity.
- Protection and reduction in organ involvement improved with higher passage numbers of the vaccine strain.
Conclusions:
- The K168-8Ac strain elicits a robust immune response and provides partial protection against CV-A16 infection in rhesus monkeys.
- Increasing passage levels of the vaccine strain correlate with enhanced protective efficacy.
- These findings support the further development of K168-8Ac as a CV-A16 vaccine.

