Hemagglutinin-based DNA vaccines containing trimeric self-assembling nanoparticles confer protection against influenza

Abstract

Influenza viruses continue to threaten public health, and currently available vaccines provide insufficient immunity against seasonal and pandemic influenza. The use of recombinant trimeric hemagglutinin (HA) as an Ag provides an attractive alternative to current influenza vaccines. Aiming to develop an effective vaccine with rapid production, robust immunogenicity, and high protective efficiency, a DNA vaccine was designed by fusing influenza virus HA with self‐assembled ferritin nanoparticles, denoted as HA‐F. This candidate vaccine was prepared and purified in a 293–6E cell eukaryotic expression system. After BALB/c mice were immunized with 100 μg of HA‐F DNA 3 times, HA‐F elicited significant HA‐specific humoral immunity and T cell immune responses. The HA‐F DNA vaccine also conferred protection in mice against a lethal infection of homologous A/17/California/2009/38 (H1N1) virus. These results suggest that the HA‐F DNA vaccine is a competitive vaccine candidate and presents a promising vaccination approach against influenza viruses.

A biepitope, adjuvant-free, self-assembled influenza nanovaccine provides cross-protection against H3N2 and H1N1 viruses in mice

“…Ferritin is a SANP composed of 24 identical subunits with robust thermal and chemical stability [20]. Currently, our group has displayed various antigens on the surface of ferritin NPs related to many infectious diseases, such as influenza, acquired immunodeficiency syndrome, and canine distemper [21][22][23][24].…”

Gene‐encoded nanoparticle vaccine platforms for in vivo assembly of multimeric antigen to promote adaptive immunity

“…This nanovaccine, HA-F, elicited higher antibody titers and antigen-specific T-cell responses relative to both soluble monomeric and trimeric HA. In a lethal challenge, HA-F conferred complete survival and the lowest lung viral titers relative to other immunization groups (Qiao et al, 2022). DNA-launched SAPNs have also been described for SARS-CoV-2 prophylaxis.…”

Influenza and Universal Vaccine Research in China

“…The results showed that both vaccines induced high M2e-specific humoral and cellular immune responses in mice, with p-tPA-p3M2e providing more effective protection against lethal attack by the same subtype of H1N1 virus and exhibiting cross-protection against different subtypes (H9N2, H6N6 and H10N8) [ 94 ]. In addition, Qiao et al, designed a DNA vaccine called HA-F by fusing influenza virus HA with self-assembled ferritin nanoparticles, and after immunizing mice with 100 µg of this DNA vaccine three times, it showed significant HA-specific humoral and T-cell immune responses and protected mice from lethal infection by homologous H1N1 virus, indicating that HA-F is a competitive vaccine candidate [ 95 ]. In summary, DNA vaccines hold promise for development as universal, broad-spectrum influenza virus vaccines.…”