Abstract
In the midst of the ongoing COVID-19 coronavirus pandemic, influenza virus remains a major threat to public health due to its potential to cause epidemics and pandemics with significant human mortality. Cases of H7N9 human infections emerged in eastern China in 2013 and immediately raised pandemic concerns as historically, pandemics were caused by the introduction of new subtypes into immunologically naïve human populations. Highly pathogenic H7N9 cases with severe disease were reported recently, indicating the continuing public health threat and the need for a prophylactic vaccine. Here we review the development of recombinant influenza virus-like particles (VLPs) as vaccines against H7N9 virus. Several approaches to vaccine development are reviewed including the expression of VLPs in mammalian, plant and insect cell expression systems. Although considerable progress has been achieved, including demonstration of safety and immunogenicity of H7N9 VLPs in the human clinical trials, the remaining challenges need to be addressed. These challenges include improvements to the manufacturing processes, as well as enhancements to immunogenicity in order to elicit protective immunity to multiple variants and subtypes of influenza virus.
Highlights
In addition to pandemic COVID-19 virus infections, influenza virus remains a major threat to public health and causes significant morbidity and mortality worldwide from annual seasonal epidemics and periodic pandemics [1,2]
We showed that i.n. vaccination with the H5/H7/H9 triple-subtype virus-like particles (VLPs) induced vaccination with the H5/H7/H9 triple-subtype VLP induced immune responses and protected ferrets immune responses and protected ferrets from experimental challenges with three subtypes of avian from experimental challenges with three subtypes of avian influenza viruses [50]
The results demonstrate that matched anti-HA immunity elicited by a VLP preparation may suffice to prevent morbidity and mortality caused by lethal secondary bacterial infection
Summary
In addition to pandemic COVID-19 virus infections, influenza virus remains a major threat to public health and causes significant morbidity and mortality worldwide from annual seasonal epidemics and periodic pandemics [1,2]. The majority of current vaccine manufacturers prepare vaccines either as split subvirions or live-attenuated viruses, and they are mostly dependent on fertilized chicken eggs as production “bioreactors” This technology is unlikely to meet the vaccine production demand during the rapid pandemic spread [18]. The novel recombinant VLP vaccine platforms included VLPs prepared in mammalian, insect, and plant expression systems. Recombinant VLPs are morphologically and biochemically similar to the wild type influenza virus (Figure 2); they lack viral genetic material and are unable to replicate and cause infection. Cell culture-based production of VLPs can potentially overcome limitations of classic influenza vaccines [36]. The use of VLPs expressed from mammalian cell platform has advantages for VLP production such as flexibility and a similar glycosylation pattern to the Trichoplusia fully protected against human virus. The transient transfection addressed by preparing stable cell line of corresponding genes
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