Universal Influenza Vaccines - A Short Review

Influenza virus is one of the most important respiratory pathogens with significant medical and economic burdens [1-3]. It belongs to genera A, B and C of the family Orthomyxoviridae with type A viruses being the primary pathogens claimed for seasonal and pandemic influenza outbreaks [4]. Type A viruses can be further divided into different subtypes based on the serotypes of their main surface antigens hemagglutinin (HA) and neuraminidase (NA) [5]. So far, 17 HA and 9 NA subtypes have been identified. Phylogenetically, 16 HA subtypes are categorized into two groups (H1, H2, H5, H6, H8, H9, H11, H12, H13 as well as H16 in group 1, and H3, H4, H7, H10, H14 as well as H15 in group 2) [6]. Historically, H1 (H1N1), H2 (H2N2) and H3 (H3N2) have caused influenza pandemics in humans and resulted in millions of death [7]. At present, H1N1 and H3N2 viruses are causing epidemic infections in humans and constitute the main components of seasonal influenza vaccines. However, the efficacy of current influenza vaccine is limited due to the antigenic drift. Further, the occasional antigenic shift of HA and NA may cause the emergence of new influenza pandemics. In addition, non-human influenza viruses may acquire the capacity for transmission in humans as well [8]. With the frequent infection by highly pathogenic avian influenza A (HPAI) H5N1 in humans in recent years, and the most recent human infection by a novel avian influenza virus (H7N9) in China [9,10], this concern has become more urgent. Although current influenza vaccines are effective in battling closely matched viruses, the major hurdles are the need to produce new vaccines every season, the uncertainty in choice of the correct strains, and the inability to prevent a new influenza pandemic. Improved vaccines inducing broadly protective immune responses against multiple type A influenza viruses, namely universal influenza vaccines, are needed, not only for seasonal but also for pandemic influenza prevention. Conserved epitopes are potential immunogens for such vaccines [11,12]. Combined strategies including improved design of antigens, integrated molecular adjuvants, new antigen delivery techniques and vaccination regimens should be considered together to overcome current obstacles in the development of a universal influenza vaccine [6,13-17].