Assessment of Route of Administration and Dose Escalation for an Adenovirus-Based Influenza A Virus (H5N1) Vaccine in Chickens

Abstract

Highly pathogenic avian influenza (HPAI) virus causes one of the most economically devastating poultry diseases. An HPAI vaccine to prevent the disease in commercial and backyard birds must be effective, safe, and inexpensive. Recently, we demonstrated the efficacy of an adenovirus-based H5N1 HPAI vaccine (Ad5.HA) in chickens. To further evaluate the potential of the Ad5.HA vaccine and its cost-effectiveness, studies to determine the minimal effective dose and optimal route of administration in chickens were performed. A dose as low as 10 7 viral particles (vp) of adenovirus-based H5N1 vaccine per chicken was sufficient to generate a robust humoral immune response, which correlated with the previously reported level of protection. Several routes of administration, including intratracheal, conjunctival, subcutaneous, and in ovo routes, were evaluated for optimal vaccine administration. However, only the subcutaneous route of immunization induced a satisfactory level of influenza virus-specific antibodies. Importantly, these studies established that the vaccine-induced immunity was cross-reactive against an H5N1 strain from a different clade, emphasizing the potential of cross-protection. Our results suggest that the Ad5.HA HPAI vaccine is safe and effective, with the potential of cross-clade protection. The ease of manufacturing and cost-effectiveness make Ad5.HA an excellent avian influenza vaccine candidate with the ability to protect poultry from HPAI virus infection. Considering the limitations of the influenza vaccine technology currently used for poultry applications, any effort aimed at overcoming those limitations is highly significant.

Immunogenicity of an adenoviral-based Middle East Respiratory Syndrome coronavirus vaccine in BALB/c mice

“…Adenovirus 5 (Ad5)-vectored candidate vaccines induce potent and protective immune responses against several pathogens in humans and a variety of animals [18,[23][24][25][26][27][28][29][30][31][32][33]. Although a trial of a candidate DNA/rAd5 HIV-1 preventive vaccine showed lack of efficacy [37] and the high prevalence of pre-existing anti-Ad5 immunity may have been a major limitation [38] in humans, replication-defective adenovirus vaccines are among the most attractive vectors for veterinary vaccine development, given the relative speed and low cost of development and production.…”

Novel Technologies for Vaccine Development

“…Immunization with Ad-based vaccines using different routes and dose regimens has been shown to have a significant effect on the type and strength of the induced immune responses (Holst et al 2010;Suda et al 2011;Steitz et al 2010). For example, parenteral administration is associated with diminished vaccine efficacy due to the presence of preexisting anti-Ad immunity.…”

Advances and Future Challenges in Recombinant Adenoviral Vectored H5N1 Influenza Vaccines

“…Immunization with rAd vectored vaccines by different routes and doses can have a significant effect on the type and strength of the induced immune responses [98,99,100,101]. Similar to traditional vaccines, rAd vectored vaccines are usually delivered parenterally to stimulate humoral and cellular immune responses.…”

“…Improved vaccines are required in order to induce rapid and sustained broad immunity, to allow mass vaccination campaigns and DIVA (differentiation between infected and vaccinated animals) strategies. The potency of a rAd vectored H5N1 vaccine expressing HA protein of A/Vietnam/1203/04 has been demonstrated [101,118] and can be significantly enhanced by fusion of HA protein with chicken CD154 in chickens [167]. Additionally, chickens can be effectively immunized by in ovo administration or aerosol spray of rAd vectored AI vaccines [125,168].…”