Adenoviral vectors as novel vaccines for influenza

Abstract

Objectives Influenza is a viral respiratory disease causing seasonal epidemics, with significant annual illness and mortality. Emerging viruses can pose a major pandemic threat if they acquire the capacity for sustained human-to-human transmission. Vaccination reduces influenza-associated mortality and is critical in minimising the burden on the healthcare system. However, current vaccines are not always effective in at-risk populations and fail to induce long-lasting protective immunity against a range of viruses. Key findings The development of 'universal' influenza vaccines, which induce heterosubtypic immunity capable of reducing disease severity, limiting viral shedding or protecting against influenza subtypes with pandemic potential, has gained interest in the research community. To date, approaches have focused on inducing immune responses to conserved epitopes within the stem of haemagglutinin, targeting the ectodomain of influenza M2e or by stimulating cellular immunity to conserved internal antigens, nucleoprotein or matrix protein 1. Summary Adenoviral vectors are potent inducers of T-cell and antibody responses and have demonstrated safety in clinical applications, making them an excellent choice of vector for delivery of vaccine antigens. In order to circumvent pre-existing immunity in humans, serotypes from non-human primates have recently been investigated. We will discuss the pre-clinical development of these novel vectors and their advancement to clinical trials.

Recombinant Adenoviruses Displaying Matrix 2 Ectodomain Epitopes on Their Fiber Proteins as Universal Influenza Vaccines

“…AdVs have been widely modified to function as vaccine vectors for the following advantages: broad tropism, high transduction efficiency, potent immune response induction, and excellent safety profile (28). Moreover, the production of the AdV-based influenza vaccine is independent of chicken embryos (29).…”

Проблема Создания Универсальной Противогриппозной Вакцины

“…В качестве векторов, экс-прессирующих гриппозные антигены, используют различные ДНК-содержащие вирусы, а именно: аде-новирус [80], герпесвирус [81], бакуловирус [82] или поксвирус [83]. Так, при применении аденовирусно-го вектора показано, что трехкратная иммунизация плазмидой (50 мкг), содержащей последовательности консервативных белков NP и M2 вируса гриппа A, с последующим интраназальным заражением двумя аденовирусными векторами, экспрессирующими эти же белки, полностью защищала мышей и хорьков от гибели и потери веса при заражении вирулентным вирусом A/FM/1/47 (H1N1) или высокопатогенным штаммом вируса гриппа птиц подтипа H5N1 [84,85].…”

Immunogenicity of an adeno-vector vaccine expressing the F protein of a respiratory syncytial virus manufactured from serum-free suspension culture

“…Ad has been proven as a potential a vaccine vectors in multiple successful preclinical studies (Coughlan et al, 2015;Kohlmann et al, 2009;Shao et al, 2009). Ad is a strong DC activator, which enzymatically processes and presents antigenic peptides associated with MHC class I and II molecules on the surface, and subsequently coordinates and stimulates T helper and cytotoxic T-cell responses (Barouch and Nabel, 2005;Coughlan et al, 2015).…”