SEROLOGICAL ASSAYS USED TO MEASURE VACCINE-INDUCED RESPONSES AGAINST FOOT-ANDMOUTH DISEASE VIRUS

ANNA LUDI; ALEJANDRA CAPOZZO; RICHARD REEVE; DAVID PATON

Bangkok

Congreso; Global Foot-and-Mouth Disease Research Alliance 2019 Scientific Meeting; 2019

Global Foot and Mouth Disease Research Alliance

The Foot-and-mouth disease virus (FMDV) vaccines currently used worldwide are based on chemically inactivated whole viral particles adjuvanted with oil or with aluminium hydroxide and saponins. The protection provided by vaccination is serotype and somewhat strain specific, so vaccines should be selected to protect against all of the strains circulating in the region where it is applied. Vaccine application and immunity should be monitored to warrant effectiveness in the field. Vaccine-induced protection is mainly mediated by antibodies and canthen be predicted by serology, avoiding the need of a challenge to assess vaccine efficacy. However, the selection of the most adequate test is complicated as the different serological assays provide information on a limited aspect of the humoral immune response. Protection from any acute virus infection using inactivated vaccines has been associated with specific antibody levels and a combination of antibody properties such as in vitro neutralizing capacity, avidity, opsonophagocytic activity and ability to mediate antibody-dependent cellular cytotoxicity; the two latter related to the isotype of the antibody. Currently (and for over more than 50 years) only two aspects of the humoral responses elicited by FMDV vaccines have been addressed: the amounts of systemic antibodies and the biological capacity of these antibodies to prevent virus infection in cell culture; using liquid phase blocking or solid phasecompetition ELISAs and the virus neutralization test (VNT), respectively. Information provided by these tests has been useful for selecting vaccines to be used in the field and for assessing vaccine efficacy; however, many failures in the prediction and poor correlation between these assays have been reported that can result from disregarding other aspects of the FMDV- specific antibody repertoire. ELISAs aimed at measuring antibody avidity and at characterizing the IgGisotypes against FMDV have been developed using purified whole viral particles as capture antigen. They appear so far to be more accurate in predicting cross-protection than the currently used tests. Just as capsid integrity is vital for vaccine performance, it is important to consider its significance in serological tests that aim to measure antibodies against surface exposed epitopes. The lack of correlation between ELISAs or VNT and protection may be influenced by the presence of disassembled particles (virus integrity is not monitored during antigen preparation for blocking ELISAs) that will bind antibodies against internal epitopes that are not relevant for protection.A precise interpretation of the information provided by each of the available serological assays, covering different aspects of the humoral immune response elicited by a vaccine, can be useful to monitor the presence of protective antibodies in a vaccinated animal population and for deciding if a vaccine is likely to be effective in the field. Assays giving a broader overview of ormore specific insight into the antibody response can help us to understand the mechanisms underlying protective and cross- reactive response. This is paramount for dissecting the role of the different features of anti-FMDV antibodies in protection and for selecting an appropriate assay or combination of assays to monitor vaccine induced responses in the field