Nasal SARS-CoV-2 vaccine outperforms existing vaccines in preclinical trials

A recent study published in the journal natural microbiologyinvestigators are evaluating the role of a live attenuated vaccine (LAV) sCPD9 in inducing systemic and mucosal immunity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants.

study: Live attenuated vaccine sCPD9 induces superior mucosal and systemic immunity against SARS-CoV-2 variants in hamsters. Image Credit: TopMicrobialStock / Shutterstock.com

prologue

The coronavirus disease 2019 (COVID-19) vaccine is currently administered by the intramuscular route and is effectively Neutralizing antibody, effector and central memory T cells, germinal center B cells, long-lived plasma cells, and nasal resident CD8+ T cells. The intramuscular route is less effective in promoting long-lasting mucosal immunoglobulin A (IgA) and IgG responses, as well as lung tissue-resident memory cell responses.

In particular, mucosal antibodies are important in reducing viral infectivity and spread at the site of entry. Tissue-resident memory cells have a faster recall response and, due to their local location, can recognize cognate antigens more quickly.

About research

In this study, researchers compare immune responses preclinically. effectiveness of Pfizer-BioNTech BNT162b2 messenger ribonucleic acid (mRNA) COVID-19 vaccine, adenoviral vector spike vaccine Ad2-spike, and LAV sCPD9 in Syrian hamsters.

The efficacy and mechanism of action of the evaluated vaccines were evaluated in heterologous SARS-CoV-2 Delta variant challenge conditions. To this end, Syrian hamsters were vaccinated with one dose and exposed to the SARS-CoV-2 delta variant 21 days after vaccination to assess its efficacy. He received two doses of vaccine and contracted the virus 14 days after his booster dose.

Histopathology was used to examine attacked hamsters and identify lung damage caused by infection. Single-cell RNA sequencing (scRNA-seq) was performed on lung specimens to establish a correlation between inflammatory levels and cellular responses.

Humoral responses in hamsters were assessed by analyzing sera collected before and after vaccination and determining their neutralizing capacity against SARS-CoV-2 variants at various time points.

result

All vaccinations protected hamsters from weight loss due to SARS-CoV-2 infection. However, a single dose of the vaccine did not completely protect him from SARS-CoV-2 Delta infection because viral RNA was still present in the airways. The sCPD9 vaccine was the only tested vaccine that successfully reduced viral titer replication to undetectable levels within 2 days post-challenge (dpc).

The overall efficacy of the SARS-CoV-2 vaccine was enhanced by prime-boost vaccination. All groups showed detectable viral RNA in oropharyngeal specimens and lungs, despite a significant reduction after prime-boost vaccination. Nevertheless, sCPD9-based vaccination was more effective in reducing viral RNA levels.

Vaccinated animals had significantly reduced lung replicable vial levels at 2 days post-challenge (dpc). Only the sCPD9 booster vaccine effectively reduced the proportion of replicating virus below the detection threshold regardless of whether the entire vaccination series was heterologous or homogenous.

Moreover, sCPD9 was highly effective in preventing inflammation and pneumonia after one vaccination. This was demonstrated by lower levels of integrated lung area along with lower scores for bronchitis, edema, and lung inflammation.

Animals with different vaccination schedules showed more pronounced bronchial hyperplasia. Prime-boost regimens showed similar trends, and mRNA vaccines showed better histologic results with allogeneic boosts.

Allogeneic sCPD9 prime-boost vaccination provided better lung protection against inflammation. Hamsters vaccinated with heterologous and homologous sCDP9 vaccines showed a reduction in inflammation- and infection-related genes in the lung transcriptome.

Sera from sCPD9 vaccinees showed higher neutralization capacity against the ancestral SARS-CoV-2 variant B.1 compared to other groups. sCPD9 sera effectively neutralized the Beta and Delta mutants, as well as the Omicron BA.1 subline.

Neutralizing capacity to Omicron BA.1 was decreased in all cohorts and sCPD9 sera were associated with significant neutralization. Neutralizing antibodies increased by 5 dpc over time in all cohorts with challenge infection.

Hamsters vaccinated with sCPD9 or mRNA vaccines and prime only produced more neutralizing antibodies than hamsters vaccinated with prime only. Booster vaccination improved the serum neutralization capacity of different variants, with Omicron BA.1 showing the highest neutralization escape capacity among the variants tested.

Hamsters vaccinated with mRNA+sCDP9 and prime-boost sCDP9 generated marked IgG antibody responses against the SARS-CoV-2 spike, nucleocapsid protein, and open reading frame (ORF)-3a. By comparison, hamsters vaccinated with prime-boost mRNA and Ad2 only spike protein.

Conclusion

The results of this study showed a comparison of vaccines across different platforms, including the new LAV, which offers better protection against SARS-CoV-2 infection than other types of COVID-19 vaccines. Importantly, these findings on immune enhancement by heterologous prime-boost vaccination are consistent with other recent studies utilizing systemic priming and intranasal boosting with Ad-2 vector or mRNA vaccines.

Anti-SARS-CoV-2 IgA levels in nasal mucosa are significantly higher in sCPD9-vaccinated animals. Animals vaccinated with sCPD9 showed significant improvement in protection against viral replication, lung inflammation, and tissue damage. Animals that received sCPD9 showed broader antigen recognition, likely due to a key feature of her LAV.