Novel Viral Vectored Vaccines for the Prevention of Influenza

Abstract

Influenza represents a substantial global healthcare burden, with annual epidemics resulting in 3-5 million cases of severe illness with a significant associated mortality. In addition, the risk of a virulent and lethal influenza pandemic has generated widespread and warranted concern. Currently licensed influenza vaccines are limited in their ability to induce efficacious and long-lasting herd immunity. In addition, and as evidenced by the H1N1 pandemic in 2009, there can be a significant delay between the emergence of a pandemic influenza and an effective, antibody-inducing vaccine. There is, therefore, a continued need for new, efficacious vaccines conferring cross-clade protection-obviating the need for biannual reformulation of seasonal influenza vaccines. Development of such a vaccine would yield enormous health benefits to society and also greatly reduce the associated global healthcare burden. There are a number of alternative influenza vaccine technologies being assessed both preclinically and clinically. In this review we discuss viral vectored vaccines, either recombinant live-attenuated or replication-deficient viruses, which are current lead candidates for inducing efficacious and long-lasting immunity toward influenza viruses. These alternate influenza vaccines offer real promise to deliver viable alternatives to currently deployed vaccines and more importantly may confer long-lasting and universal protection against influenza viral infection.

Cooperativity Between CD8+ T Cells, Non-Neutralizing Antibodies, and Alveolar Macrophages Is Important for Heterosubtypic Influenza Virus Immunity

“…The specific priming agent used has been reported to confer differences in protection against influenza virus in several vaccine studies [45], [46]. Thus, mice were primed with LCMV Armstrong, Listeria-GP33 (LM-GP33), or Vaccinia-GP33.…”

Advances and Future Challenges in Recombinant Adenoviral Vectored H5N1 Influenza Vaccines

“…Included in the list of alternative strategies are the recombinant adenoviral (rAd) vectored H5N1 vaccines, which are promising candidates that induce rapid and long-term cross-protective immunity against continuously evolving H5N1 viruses [31,32,33,34,35]. …”

“…VLP based vaccines can induce both humoral and cellular immunity in nonclinical studies and have looked very promising in clinical trials [178]. rAd vectored H5N1 vaccines are considered lead-candidates among DNA based and viral vectored influenza vaccines [35]. Based on the promising results of rAd H5N1 vaccine in nonclinical and clinical studies and the increasing clinical experience with rAd vectored vaccines against various infectious pathogens, we believe that the rAd vectored nasal influenza vaccines hold great promise for the influenza pandemic preparedness.…”

Progress on adenovirus-vectored universal influenza vaccines

“…rAd is a respiratory virus. An adenoviral vector can mimic natural infection 6 and induce long-term cross-protective immunity toward influenza viruses, 7,8 and many studies indicate that rAd induces effective transgene-specific humoral 9 and cellular immune responses. 10,11 Therefore, the adenovirus vector is one of the most promising types of vaccine vectors.…”