**Peter Pushko \* and Irina Tretyakova**

Medigen, Inc., 8420 Gas House Pike, Suite S, Frederick, MD 21701, USA; itretyakova@medigen-usa.com **\*** Correspondence: ppushko@medigen-usa.com

Received: 2 April 2020; Accepted: 27 April 2020; Published: 8 May 2020

**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.

**Keywords:** H7N9, pandemic influenza A; avian flu; IAV; VLP vaccine
