Spotlight on avian pathology: the importance of recombinant vector platform technologies in poultry vaccination

ABSTRACT

The use of novel vector vaccines (viral, bacterial and apicomplexan) can have a significant impact on the control of poultry disease. They offer a cost effective, convenient and effective means of mass vaccine delivery combined with the ability to switch on both antibody and cell-mediated immunity. In addition, recent viral vector constructs have enabled farmers to vaccinate against up to three important pathogens with a single in ovo administration. As the technology develops, it is likely that this means of vaccine administration will be utilized further and it will play a key role in the control of both existing and new emerging diseases of poultry in the future.

KEYWORDS:

• Vaccine
• vector
• platform
• fowlpox
• HVT
• Salmonella
• Eimeria
• immunity

Background

The outstanding efforts to create and licence a vaccine to combat COVID-19, and the rapid development of the ChAdOx1 nCoV-19 viral vector vaccine from the Jenner Institute, Oxford in particular, have led me to reflect on the significant contributions that veterinary medicine has made to vaccine innovation. Indeed, many of the platform technologies that are currently being investigated for a vaccine against SARS-CoV-2 have already been successfully developed and licenced for use in veterinary vaccines (e.g. viral vectors, bacterial vectors, subunits, virus-like particles, nucleic acids and peptides) (Francis, 2018). Of these technologies, the development of vectors has arguably been the most successful, and their use in the control of poultry disease has been particularly notable. Attenuated/modified live vaccines offer a number of distinct advantages over conventional inactivated/killed and subunit vaccines. By replicating within the host, they more accurately mimic natural infection, they are often easy to administer, they provide long-lived immunity, and they can stimulate a more comprehensive immune response, including humoral antibodies, secretory antibodies and cytotoxic T-cells. For these reasons, scientists have looked at ways of delivering subunit or peptide vaccines using live recombinant vectors in order to elicit in vivo antigen expression and potentially improve on the efficacy of a more traditional attenuated vaccine approach.

Viral vector vaccines

The majority of virus vector vaccine studies have concentrated on relatively large DNA viruses, in particular poxviruses, herpesviruses and adenoviruses. We can trace the early examples of viral vectors being developed for poultry vaccination back to the late 1980s and early 1990s when some of the poxvirus vectors were examined for their expression of immunogenic proteins from Newcastle disease (ND) virus. The most promising of these was the fowlpox virus (Boyle & Coupar, 1988), which has subsequently been used to produce commercial vaccines against ND, avian influenza H5, Mycoplasma gallisepticum and infectious laryngotracheitis (ILT). The discovery that the herpesvirus of turkeys (HVT) could elicit protective immunity against Marek’s disease (MD) in chickens (Churchill et al., 1969) has provided an alternative viral vector with a more significant potential for dual protection against two important diseases of poultry. This potential was first exploited in 1992 by using it as a vector for the fusion protein or the haemagglutinin-neuraminidase genes from the ND virus (Morgan et al., 1992), and subsequently in 1995 to express the VP2 protein of infectious bursal disease (IBD) virus (Darteil et al., 1995). This has led to the development of a range of bivalent vaccines against both MD plus ND, IBD, avian influenza, Mycoplasma gallisepticum or ILT. More recently, in 2017, the first trivalent vector vaccine (Innovax-ND-IBD, Merck Animal Health, Madison, NJ) was licenced for use in poultry against MD, ND and IBD, and this was followed in 2020 by the licencing of Vaxxitek HVT + IBD + ND and Vaxxitek HVT + IBD + ILT from Boehringer Ingelheim, Ingelheim, Germany. A further development of this MD serotype 3 vector has been achieved by adding a serotype 2 (SB-1) virus to the vaccine in order to enhance protection against virulent serotype 1 field strains of MD virus. Another viral vector for poultry has been developed by engineering a lentogenic paramyxovirus type 1 vector NDV to express the haemagglutinin protein of avian influenza H7 (Swayne et al., 2003). All these viral vector vaccines offer the potential for safe, convenient and rapid mass delivery using several routes of administration, including in ovo. Furthermore, by targeting multiple diseases with a single vaccine there should be opportunities to reduce the cost and attain greater end-user acceptability, resulting in the increase in uptake of the vaccine.

Bacterial vector vaccines

Studies on the rational attenuation of bacteria in order to produce suitable oral vaccines have also introduced the possibility of using these bacterial strains as vectors for foreign proteins. Initial studies looked at generating auxotrophic mutants by removing or modifying important genes (Galán & Curtiss, 1989). The majority of the work in this area has concentrated on producing invasive strains of bacteria that are sufficiently attenuated so as not to cause any pathogenic disease signs when delivered orally or parenterally to the host. Examples of such attenuated bacterial vectors being used for the experimental delivery of different antigens in poultry include those against coccidiosis (Du & Wang, 2005), influenza (Layton et al, 2009), necrotic enteritis (Kulkarni et al., 2010) and Campylobacter (Adams et al., 2019). Indeed, an attenuated Salmonella vectored vaccine against necrotic enteritis called AVERT NE was recently licenced by Huvepharma HQ, Sofia, Bulgaria, in 2020.

Apicomplexan vector vaccines

Another approach to the development of novel vector vaccines for poultry has arisen from the potential application of apicomplexan parasites as vectors. The development of methodologies which utilize genetic complementation by transfection in Eimeria has provided an opportunity for live anticoccidial vaccine strains to be used as vectors for antigens from other pathogens, including bacteria and viruses. This approach is now being explored for the development of vaccines against Campylobacter jejuni (Clark et al., 2012), Toxoplasma gondii (Tang et al., 2016) and IBD (Marugan-Hernandez et al., 2016). A further natural development of this technology is to use one strain of Eimeria (e.g. an E. tenella vaccine strain) to deliver immunodominant antigens of another strain or species (e.g. E. maxima) in order to elicit simultaneous protection against two important parasites of poultry (Tang et al., 2018).

Concluding remarks and future directions

Thus, the advent of vector vaccine platform technologies has had a significant impact on the poultry industry, offering a simple, convenient, cost effective, safe and efficacious means of vaccine delivery along with the potential for the induction of long lasting humoral, mucosal and cell-mediated immunity. The latest viral vectors with the ability to immunize birds against three important pathogens after a single administration is an important advance in the technology. It seems likely that we will see similar advances with both bacterial and apicomplexan vectors. Thus, the potential of such vectors for the mass administration of relatively low-cost vaccines is significant. As a result, I feel that vector vaccines will play an increasingly significant role in the control of existing and new emerging diseases of poultry in the future.

Disclosure statement

No potential conflict of interest was reported by the author.