Progress in combination vaccines and the co-administration of influenza virus and SARS-CoV-2 vaccines

Abstract

COVID-19 and seasonal influenza have taken a huge toll on the global economy and global health. Given the potential of COVID-19 to transform into a chronic epidemic akin to seasonal influenza, the influenza virus and SARS-CoV-2 will continue to be a significant threat to healthcare for some time to come. Coinfection involving the two viruses has been proven to worsen the severity of the illness, as evidenced by clinical observational data. Vaccination remains the most effective measure in the prevention and treatment of infectious diseases. In addition, the coadministration of influenza virus and SARS-CoV-2 vaccines offered greater benefits than either vaccine alone. Combination vaccines are also a major hotspot in novel vaccine development. This review highlights the advancements in the development of combined vaccines for COVID-19 and seasonal influenza, as demonstrated in animal studies and clinical trials, and emphasizes the importance of a combined vaccine.

Keywords: SARS-CoV-2; coadministration; coinfection; combination vaccines; influenza virus.

Figure 1

The immune response after infection with the influenza virus and SARS-CoV-2. (A) When exposed to the influenza virus and SARS-CoV-2, unvaccinated Individuals cannot produce the corresponding antibodies and effector T cells against the influenza virus and SARS-CoV-2, thus, they will be infected with the influenza virus and SARS-CoV-2. (B) When exposed to the influenza virus and SARS-CoV-2, individuals vaccinated with the influenza virus vaccine can produce the corresponding antibodies and effector T cells against the influenza virus, thus, they will be infected with SARS-CoV-2. (C) When exposed to the influenza virus and SARS-CoV-2, individuals vaccinated with the SARS-CoV-2 vaccine can produce the corresponding antibodies and effector T cells against SARS-CoV-2, thus, they will be infected with the influenza virus. (D) When exposed to the influenza virus and SARS-CoV-2, individuals vaccinated with the influenza virus vaccine and SARS-CoV-2 vaccine can produce the corresponding antibodies and effector T cells against the influenza virus and SARS-CoV-2, thus, the individuals cannot be infected by either virus.

Figure 2

Both the sialic acid receptor (influenza virus receptor) and ACE2 are present in respiratory epithelial cells, including the nasal mucosa, trachea, bronchi, and alveoli.

Figure 3

The individuals vaccinated with the influenza virus vaccine were less likely to be infected with SARS-CoV-2 and develop severe COVID-19.

Figure 4

The platforms for vaccine development. (A) Influenza virus vector platform: The gene of RBD (receptor binding domain) or T-cell epitope of SARS-CoV-2 is inserted into the influenza virus genome. RBD or T-cell epitope is expressed on the surface of influenza virus particles. (B) Ad vector platform: The fusion gene of RBD of SARS-CoV-2, the stalk domain of hemagglutinin (HA) of influenza virus, and human ferritin is inserted into the adenovirus genome. The gene is delivered into the body by the recombinant adenovirus. The fusion immunogen self-assembles into nanoparticles. (C) VSV vector platform: The fusion gene of RBD of SARS-CoV-2 and Matrix Protein 2 Ectodomain (M2e) of the influenza virus are inserted into the vesicular stomatitis virus (VSV) genome. The gene is delivered into the body and expressed. (D) Nucleic acid platforms: A mixture of influenza virus RNA vaccine and SARS-CoV-2 RNA vaccine generates the combined vaccines. (E) Protein platforms: A mixture of the RBD-trimer vaccine and the HA1-trimer vaccine generates the combined vaccines. (F) VLP platform: Incorporation of GPI-RBD-GM-CSF (glycosylphosphatidylinositol, RBD, and granulocyte-macrophage colony-stimulating factor) fusion protein and virus-like particles (VLPs) generates the combined vaccines.