Up-to-date Progress in the R&D of Anti-influenza Vaccines

Influenza is a respiratory infectious disease caused by the influenza virus. About 5% to 10% of people in the world are infected with influenza every year. According to the scale, influenza epidemics can be divided into influenza pandemics and seasonal influenza epidemics. There are four main types of viruses that cause seasonal influenza epidemics, namely the IAV subtype H1N1 and H3N2 and two IVB subtypes. The annual seasonal influenza epidemics cause 3 million to 5 million severe cases and 290,000 to 650,000 respiratory disease related deaths worldwide, posing a serious threat to public health security. So far, 5 influenza pandemics have been recorded, which are Spain H1N1 influenza in 1918, Asia H2N2 influenza in 1957, Hong Kong H3N2 influenza in 1968, H1N1 avian influenza in 2005, and H1N1 influenza in 2009. According to the antigenicity of virus matrix 1 (M1) and nucleoprotein (NP), influenza viruses can be divided into IAV, IBV, ICV, and IDV. IAV, IBV, and ICV can infect human and cause respiratory diseases. IDV mainly infects cattle, and it is not yet known whether it can infect humans. Various animals can be infected by IAV, such as birds, pigs, horses, and marine mammals, and cause pandemics. According to the molecular characteristics of Hemagglutinin (HA) and Neuraminidase (NA) on the virus surface, so far, 18 HA subtypes (H1~H18) and 11 NA subtypes (N1~N11) have been identified. The genome of IAV includes 8 independent RNA fragments, which encode at least 12 proteins with well-defined functions. In general, both IAV and IBV can cause influenza, and IAV is a more critical factor leading to seasonal and epidemic outbreaks. ICV mainly infects children, causing generally mild symptoms. The recently discovered IDV is still under study, of which the impact on humans has not yet been revealed. Influenza virus is a segmented single-stranded negative sense RNA virus of the Orthomyxoviridae family (https://www.creative-biolabs.com/vaccine/vaccines-for-virus-from-orthomyxoviridae-family.htm). The virus particles are usually spherical, with a diameter of 80-120nm, and some filaments are about a few microns long. Influenza virus is mainly composed of three parts, namely core, matrix protein, and viral envelope. Influenza vaccine is the most effective way of prevention, but the protective efficacy of currently marketed vaccines varies from year to year, depending on the antigenic match between circulating virus and vaccine strain. Since influenza viruses are prone to mutate during replication, influenza vaccines must be replaced with strains and re-vaccinated every year. In terms of drug, neuraminidase inhibitors such as oseltamivir, zanamivir, and peramivir are effective treatments for Type A and Type B influenza. Early application of anti-influenza virus drugs, especially within 48 hours of onset, can significantly reduce the incidence of severe symptoms and death. However, drug prevention cannot replace vaccination. It can only be used as an emergent treatment for people at high risk of severe influenza who have not been vaccinated or have not gained immunity after vaccination. AudenzrnIn February 2020, the FDA approved Seqirus's Audenz for active immunization of people 6 months and older, which is the first adjuvant, cell-based vaccine (https://www.creative-biolabs.com/vaccine/cell-based-vaccines.htm) (monovalent) designed to prevent H5N1 influenza during a pandemic. Audenz combines the MF59 adjuvant and cell-based antigen manufacturing technology, which can enhance and expand the body's immune response by inducing antibodies against the mutated virus strain. Fluad QuadrivalentrnIn February 2020, the FDA approved the first adjuvant quadrivalent influenza vaccine, Fluad Quadrivalent, to help elderly people aged 65 and above protect against seasonal influenza. The vaccine was also developed by Seqirus. In June 2020, the vaccine was also approved in Europe. Fluad Quadrivalent includes 2 IAV strains and 2 IBV strains, which uses the same MF59 adjuvant technology as Fluad (aTIV), designed to generate a strong, extensive, and long-lasting immune response. Compared with Fluad (aTIV), Fluad Quadrivalent adds an additional IBV strain. Both are adjuvant seasonal influenza vaccines for adults 65 years and older.