Current status of veterinary vaccines

Abstract

The major goals of veterinary vaccines are to improve the health and welfare of companion animals, increase production of livestock in a cost-effective manner, and prevent animal-to-human transmission from both domestic animals and wildlife. These diverse aims have led to different approaches to the development of veterinary vaccines from crude but effective whole-pathogen preparations to molecularly defined subunit vaccines, genetically engineered organisms or chimeras, vectored antigen formulations, and naked DNA injections. The final successful outcome of vaccine research and development is the generation of a product that will be available in the marketplace or that will be used in the field to achieve desired outcomes. As detailed in this review, successful veterinary vaccines have been produced against viral, bacterial, protozoal, and multicellular pathogens, which in many ways have led the field in the application and adaptation of novel technologies. These veterinary vaccines have had, and continue to have, a major impact not only on animal health and production but also on human health through increasing safe food supplies and preventing animal-to-human transmission of infectious diseases. The continued interaction between animals and human researchers and health professionals will be of major importance for adapting new technologies, providing animal models of disease, and confronting new and emerging infectious diseases.

FIG. 1.

Simplified schematic representation of immune mechanisms that can act to protect animals against invading viral, bacterial, and protozoal pathogens or against multicellular helminth parasites. Viral, bacterial, or protozoal pathogens (red ovals) that infect non-antigen-presenting cells can be killed by cytotoxic T cells (CTL) that recognize pathogen-derived epitopes presented in conjunction with major histocompatibility complex (MHC) class I on infected cells or by antibody-dependent lysis or opsonization of infected cells expressing pathogen molecules. Extracellular pathogens, or intracellular pathogens on their way to infect other cells, can be attacked by specific circulating antibodies and either killed by lysis or agglutination or phagocytosed by macrophages and neutrophils. Both antibody and CTL induction requires help from pathogen-specific CD4 helper T cells that are activated after interaction with pathogen-derived epitopes presented in conjunction with MHC class II molecules on the surface of MHC class II⁺ antigen-presenting cells. If pathogens infect antigen-presenting cells, they can be killed directly by CD4 T cells as well as CD8 CTL through the induction of mediators such as gamma interferon (IFN-γ), reactive oxygen and nitrogen species, and indoleamine 2,3-dioxygenase (IDO). Toxins released by pathogens (red circles) can be neutralized by circulating antibodies, thereby decreasing clinical signs of infection. Multicellular helminth parasites generally do not reside within host cells and are too large to be phagocytosed; therefore, they usually require alternative immune killer mechanisms mediated by antibody-directed actions of mast cells and eosinophils. Essential secreted proteins and toxins derived from the worms (brown circles) may also be neutralized by antibodies and thereby interfere with parasite growth.

FIG. 2.

Simplified representation of the reverse genetic approach used to construct the chimera vaccine Poulvac FluFend i AI H5N3 RG to protect poultry against the pathogenic H5N1 virus. The HA gene was removed from an H5N1 virus (from a recent Asian outbreak), inactivated by removing the polybasic amino acid sequences, and combined with the NA gene from an H2N3 virus onto an H1N1 “backbone” virus. An immunoassay able to specifically detect antibodies against N3 and N1 proteins could be used for DIVA (i.e., N3⁺ N1⁻ indicates vaccinated, and N3⁻ N1⁺ indicates infected). (Modified from Fort Dodge Poulvac FluFend i AI H5N3 RG promotional flyer with permission.)

FIG. 3.

The key hormones of the hypothalmic-pituitary-gonadal axis. Tissues are in orange, and hormones are in green. *, hormones and gametes that have been targeted in constructing experimental and commercial vaccines.