Immunization of broiler chickens against necrotic enteritis: Progress and possibilities

Immunization of broiler chickens against necrotic enteritis (NE) caused by Clostridium perfringens is an important approach for control of this globally important disease. Although the last decade has seen considerable advances in understanding NE, including the 2008 discovery of NetB, a critically important pore-forming toxin, much remains to be discovered about the detailed pathogenesis and the basis of immunity to NE on which a scientifically designed immunization strategy must be based. The challenges include: 1. Understanding the basis and extent of immunity; 2. Induction of active immunity in newborn chicks in the face of maternal antibodies; 3. Identification and characterization of key protective antigens; 4. Defining experimental models to evaluate the protective efficacy of candidate antigens and the relevance of such models to naturally occurring NE; 5. Developing a  vaccine that is safe, easy to deliver, robust under field conditions, and inexpensive; 6. Evaluating candidate vaccines under field conditions that do not compromise the welfare of the chicken.

Considerable progress has been made in identifying antigens of importance in immunity to NE using experimental immunization-challenge models. Passive immunity in chicks obtained through breeder vaccination using bacterial supernatant that includes the alpha toxin is short-lived; however, this vaccine has been currently withdrawn from the market. In inducing an active immunity, it is striking as to how many antigens of C. perfringens can provide some level of protection against experimental NE. These include (abbreviated names): Alpha toxin, EFtu, FBA, GPD, HP, NetB, PFOR, PGM and certain pilus proteins. It seems also clear that no one antigen can provide complete protection and that a combination of antigens or artificial hybrid protein constructs seem to offer superior protection against NE. It is clearly possible to immunize actively against NE but it is also clear that the level of protection by immunization depends on the severity of the experimental challenge.

How immunity to these antigens works is not defined. There is some evidence that antibodies may interfere with the growth of C. perfringens by binding to the bacterium itself and thus preventing their multiplication rather than, for example, by toxin neutralization or opsonization. The surprising protective efficacy of some “housekeeping” rather than just of virulence-associated proteins, suggests that bacterial growth inhibition might be a plausible explanation for their effect.  Nevertheless, there seems to be a general agreement that oral immunization using recombinant vectors (example, Eimeria, Lactobacillus, Salmonella) can be a feasible option and that inducing an effective mucosal immunity is of great importance. An unresolved issue is whether NE evoked by coccidial infection requires that the C. perfringens strain be NetB-positive. If it does not, then the focus on NetB in immunization studies may be misleading, and research investment on the currently known most useful protective immunogens (alpha toxin, FBA, HP) would be more appropriate.

It is clear that immunization will be a useful but probably not perfect adjunct approach for controlling NE and that a search for the perfect antigen(s) and their delivery will likely delay progress in introducing immunization.

Keywords: Necrotic enteritis, immunization, review, progress, possibilities.

Abstract presented at the 3rd International Symposium on Alternatives to Antibiotics 2019.