Adjuvants for foot-and-mouth disease virus vaccines: recent progress

Abstract

Foot-and-mouth disease (FMD) is a highly contagious and rapidly spreading disease of cloven-hoofed animals. In most countries, animals are immunized with inactivated whole virus vaccines to control the spread of foot-and-mouth disease virus (FMDV); however, there are safety and efficacy (especially, cell-mediated immunity) concerns. Many efforts are currently devoted to the development of effective vaccines by combining the application of protective antigens together with the search for specific and targeting adjuvants that maximizes the immunogenicity with a desired immune response. In this review, we outline previous studies performed with both traditional adjuvants as well as the most promising new generation adjuvants such as ligands for Toll-like receptors (TLRs) or different cytokines, focusing mostly on their efficacy when used with FMD vaccine, and somewhat on mechanisms by which adjuvants mediate their effects.

Keywords::

• adjuvants
• FMD
• immunogenicity
• mechanisms
• vaccine

Financial & competing interests disclosure

This research was supported by a grant from the National Natural Science Foundation of China (31372422). The author has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Foot-and-mouth disease is a devastating disease of livestock that has had a significant impact on world economies and public health. Vaccination was used to control the spread of infection in many countries.

• Although the traditional inactivated vaccine is effective, there are some concerns with its use. These include potential virus escape from the production facility, the inability of inoculation with this vaccine to block the development of the carrier state and so on.

• Many efforts are currently devoted to the development of effective foot-and-mouth disease virus (FMDV) vaccines by combining the application of protective antigens together with the search for specific and targeting adjuvants that maximizes the immunogenicity with a desired immune response.

• Ligands of Toll-like receptors activate multiple innate immune pathways and stimulate the production of proinflammatory cytokines/chemokines and type I interferons. This innate immune response also supports the subsequent development of adaptive immunity, and thus can be used as adjuvants to accelerate and enhance the induction of FMDV-specific responses.

• Combinations of multiple compounds have a synergistic effect when used as adjuvants. New adjuvant development should identify novel combinations of adjuvants and formulations capable of inducing stronger and longer-lasting humoral and cellular immune responses.

• New vaccines combined with ligands of Toll-like receptors that provide immunity more rapidly and/or can be produced without the need for production of a great quantity of infectious virus required for manufacture of the traditional vaccine are being developed and may provide alternative tools to control foot-and-mouth disease.

• Mucosal adjuvants are essential for the induction of effective mucosal immunity, which may be the effective way to prevent the development of carrier animals of FMDV.