Bivalent mRNA Vaccine Targeting Foot-and-Mouth Disease Virus Serotypes A and O Elicits Antibody and Cellular Immune Responses in Mice
Background: A candidate to address limitations of inactivated vaccines
A bivalent mRNA vaccine targeting serotypes A and O of foot-and-mouth disease virus (FMDV) elicited antibody levels similar to those of an inactivated vaccine, along with a Th1-skewed immune response, in mice. Published in the international journal Vaccine, the study evaluated antigen expression in vitro and immunogenicity in mice. It did not demonstrate prevention of infection in livestock or cross-protection between serotypes.
Foot-and-mouth disease is highly contagious and poses a major threat to the livestock industry. Existing inactivated-virus vaccines are effective, but their production requires stringent biocontainment. They also have limitations in stability and immunogenicity across serotypes. The researchers proposed a vaccine candidate that packages messenger RNA (mRNA) in lipid nanoparticles (LNPs), focusing on evaluating the potential of a platform that does not require virus propagation.
Key findings: Antibody responses at different doses and a Th1-skewed profile
The vaccine design included selected and optimized immunodominant epitopes from the VP1 proteins of serotypes A and O—that is, antigen regions primarily recognized by the immune system. These were combined with a conserved T-cell epitope from the nonstructural protein 3A. After confirming antigen expression in vitro, the researchers compared immune responses in mice. The specific sequences and optimization procedures are not available in the abstract provided.
The researchers reported that antibody levels in the 5 μg mRNA vaccine group were similar to those in the 5 μg inactivated-vaccine group throughout the immune evaluation period. After a booster dose, the immune response to 10 μg of mRNA vaccine was also described as similar to that elicited by an inactivated vaccine formulated with the ISA 206 adjuvant. However, the abstract alone is insufficient to establish statistical equivalence or interpret this comparison as evidence of protection against infection.
In a liquid-phase blocking enzyme-linked immunosorbent assay (ELISA), the blocking-antibody titer against serotype A exceeded 256 at the 5 μg dose, while the titer against serotype O exceeded 128 at the 10 μg dose. Because these results were obtained at different doses, they cannot be used to directly compare the relative strength of responses to the two serotypes. Blocking-antibody measurements should also be distinguished from virus-neutralization test results and from protection rates following actual infection.
Antibody-subclass and cytokine analyses showed a high IgG2a/IgG1 ratio and high interferon gamma (IFN-γ) levels. The researchers interpreted these findings as a response skewed toward type 1 helper T cells (Th1), and explained that they were also consistent with increased activation of germinal-center B cells (GC B cells) and cytotoxic T lymphocytes (CTLs). By contrast, the ISA 206-adjuvanted vaccine showed a relatively weaker cellular immune response and a bias toward type 2 helper T cells (Th2). The findings indicate that immune-response profiles can differ even when antibody levels are similar.
Implications and outlook: Protection in livestock remains to be tested
The study supports the immunogenicity in mice of an mRNA vaccine targeting both serotypes A and O. The researchers presented it as evidence of the potential of a platform that does not use the virus for developing multivalent foot-and-mouth disease vaccines. However, blocking-antibody responses to two serotypes do not provide sufficient grounds to conclude that the vaccine offers broad protection against other variants.
The abstract provided does not specify the number of animals, route or schedule of administration, detailed statistics, or duration of immunity. Results from challenge studies assessing protection after exposing livestock to the virus are also unavailable in the abstract. Before the vaccine could be used in disease control, further studies would need to evaluate safety, protective efficacy, and durability of immunity in target livestock, as well as production and storage conditions.
This article is based on the bibliographic information and abstract of the Vaccine paper.
Foot-and-mouth disease (FMD) poses a significant threat to global livestock industries due to its high viral contagiousness. Despite inactivated viral vaccines remaining effective, their production requires stringent biocontainment and faces limitations in stability and cross-serotype immunogenicity. Here, we developed a novel bivalent mRNA@LNP vaccine targeting FMDV serotypes A and O. The design incorporated optimized immunodominant epitopes from the VP1 protein, combined with a conserved T-cell epitope from the 3A non-structural protein. We validated antigen expression in vitro and evaluated the immunogenicity of mRNA@LNP in mice. It elicited faster early immune activation and stronger humoral and cellular immune responses than the inactivated virus vaccine. Throughout the entire immunization period, the antibody levels induced by 5 μg mRNA@LNP were consistently equivalent to those of the 5 μg inactivated vaccine. Furthermore, the immune efficacy of the 10 μg mRNA dose following the booster vaccination was consistent to that of the ISA 206-adjuvanted inactivated vaccine. Liquid-blocking ELISA indicated that immunization of the mRNA@LNP induced strong blocking antibody titers against both serotype A(titer>256 at 5 μg) and serotype O(titer>128 at 10 μg). Antibody isotyping (high IgG2a/IgG1 ratio) and cytokine profiling (high IFN-γ) revealed a pronounced Th1-skewed immune response, consistent with enhanced GC B cell activation and CTL activation. In contrast, the ISA-206 adjuvanted vaccine induced a weaker cellular immune response and a more Th2-biased profile, highlighting the capacity of the mRNA vaccine to achieve not only comparable humoral immunogenicity to inactivated vaccines but also a more balanced and robust cellular immunity. These findings support mRNA vaccines as a promising, virus-free platform for multivalent FMD vaccines, offering potential solutions to current limitations and providing broader protection against FMDV outbreaks.
These results provide a basis for evaluating future veterinary vaccine candidates targeting both serotypes A and O. Developers can use the antibody levels and cellular-immunity-related measures reported in mice as a starting point to determine whether similar immune responses and actual protection against infection occur in target livestock. A platform that does not require virus propagation could help address the biocontainment burden of producing inactivated vaccines, but improvements in manufacturing safety or economic viability have not been demonstrated.
Use in cattle or pigs would require separate assessments of safety, protection following infection, and duration of immunity. Because blocking-antibody titers for serotypes A and O were reported at different doses, the current values cannot be directly translated into a common recommended dose or effectiveness in field disease control.