Intranasal mRNA-lipid nanoparticle vaccine induces significant protection against SARS-CoV-2 in hamsters

In a recent study posted on bioRxiv* US researchers use a hamster model to study efficacy and immunity of an intranasal messenger ribonucleic acid (mRNA)-lipid nanoparticle (LNP) vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) evaluated for virginity.

Background

The 2019 coronavirus disease (COVID-19) pandemic has caused more than 661 million cases and 6.7 million deaths worldwide, making it one of the most serious global emergencies associated with respiratory viruses. For one, respiratory viruses and bacteria have always been a cause for concern.

Prior to the emergence of SARS-CoV-2, respiratory viruses such as influenza virus and respiratory syncytial virus, Streptococcus pneumoniae Worldwide, nearly 2.5 million people died and more than 17.7 billion upper and lower respiratory tract infections occurred.

Current respiratory disease vaccines are administered via the intramuscular route. It primarily induces systemic immunity and lower levels of mucosal immunity. Since most respiratory viruses enter through the mucosal route, intranasal vaccines that induce local mucosal and systemic immunity target the virus at the site of entry, establish protection, and limit infection early. Show the advantage. In addition, the ease of administering intranasal vaccines by aerosolized spray provides a non-invasive and simple method with the potential to increase vaccine uptake.

About research

In this study, researchers used Syrian golden hamsters to investigate the protective efficacy and immunogenicity of an mRNA-LNP intranasal vaccine. Two LNP compositions were used to formulate the vaccine. Both her LNPs were similar to those used in Moderna’s vaccine mRNA-1273, but LNP1 has a chemically distinct ionizable lipid and LNP2 improves delivery to the airways. changed forVaccines had mRNA segments encoding SARS-CoV-2 stabilized before fusion spike protein.

Each group of 10 hamsters was intranasally immunized with two doses of either 5 μg or 25 μg mRNA-LNP vaccine or Tris/sucrose buffer (control group) at 3-week intervals. For comparison, two additional groups were immunized intramuscularly with a vaccine composed of the same mRNA segment as the mRNA-LNP vaccine combined with LNP from the mRNA-1273 vaccine.

An enzyme-linked immunosorbent assay (ELISA) was used to measure spike-specific serum immunoglobulin G (IgG) or IgA binding antibody levels. In contrast, serum was measured using the plaque reduction neutralization test (PRNT).Neutralizing antibody A titer to assess the immunogenicity of a vaccine.

Vaccinated and control hamsters were intranasally challenged with SARS-CoV-2 3 weeks after the second vaccination. The USA-WA1/2020 isolate was selected for viral challenge because hamsters are more susceptible to ancestral SARS-CoV-2 strains than recent Omicron variants. 3 days after his virus attack and 14 days after he viral load Lung and nasal turbinate weights were assessed and body weight measurements were taken daily.

In addition, we used quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to quantify subgenomic viral RNA levels in respiratory tissues and determine viral load. SARS-CoV-2 infection is known to cause severe lesions in the lungs of Syrian golden hamsters by day 3 of infection, so to understand the efficacy of mRNA Lung histopathological examination was performed on day 14. LNP vaccine in reducing pulmonary lesions. Lung tissue samples were also immunohistochemically stained for SARS-CoV-2 nucleocapsid protein to identify infected cells.

result

Results showed that SARS-CoV-2 spike-specific IgA and IgG antibodies and neutralizing antibody levels induced by mRNA-LNP intranasal vaccine were comparable to those induced by intramuscular vaccine. Antibody titers induced by the mRNA-LNP2 vaccine were significantly higher than those induced by the mRNA-LNP1 vaccine. Moreover, the IgA titers induced by the 25 μg dose of mRNA-LNP2 vaccine were higher than those induced by the 0.4 μg and 1 μg doses of intramuscular vaccine after the first and second vaccinations.

Compared with controls, viral loads in nasal turbinates and lungs of vaccinated hamsters were significantly lower 3 days after virus challenge. In the mRNA-LNP2-vaccinated group, four hamsters had viral loads below the level of detection.

High-dose mRNA-LNP intranasal and intramuscular vaccines reduced the severity of bronchial and bronchiolar inflammation. However, lung parenchymal infection levels were similar to controls.

Conclusion

Overall, intranasally administered mRNA-LNP vaccines have comparable binding to the SARS-CoV-2 spike protein as intramuscular vaccines, especially when the LNPs are modified to improve vaccine delivery to respiratory tissues. Results suggested that IgA and IgG and neutralizing antibody levels could be induced.

Given that intranasal vaccines are easy to administer and equally effective in protecting against severe disease, these intranasal mRNA-LNP vaccines can be used as booster doses to complement the main intramuscular vaccines. There is a possibility.

*Important Notices

bioRxiv publishes non-peer-reviewed, preliminary scientific reports and should not be considered conclusive, to guide clinical practice/health-related actions, or to be treated as established information .