Safety and lower airway immunogenicity of two candidate Coronavirus Disease (COVID-19) vaccines administered to the respiratory tract

Lead Research Organisation: Imperial College London
Department Name: Infectious Disease


For a COVID-19 vaccine to have maximum impact, it should not only prevent severe infection but also limit the shedding of virus so that transmission is interrupted and pandemic spread is controlled. Experience with the influenza vaccine FluEnz (which is given as a nasal spray) has shown that intranasal vaccines can be effective for both outcomes. All COVID-19 vaccines currently being trialled are delivered by injection but it is known that directly stimulating immunity at the site of infection (i.e. the nose and lung) induces specialised protective responses that may more quickly and completely control infection.

This study will test the two leading UK COVID-19 vaccines to show that they are safe, well-tolerated and capable of stimulating immune responses both in the blood and the lung when administered to the respiratory tract. Using standardised methods, we will directly compare immune responses in the blood, nose and lower airway between these two vaccines as well as with data from ongoing clinical trials of intramuscular vaccination. Thus, we will show the effect of different vaccine technologies as well as delivery method and provide the critical information required to begin further clinical trials to show the efficacy of this needle-free vaccination strategy.

Technical Summary

Substantial literature indicates that stimulation of mucosal immunity by direct antigen delivery can induced tissue-specific responses that are more effective in preventing respiratory disease, limiting viral shedding and interrupting transmission. However, in order to proceed rapidly, all COVID-19 vaccines currently in development are administered by parenteral injection.

The aim of this study is to test the safety and mucosal immunogenicity of the two leading UK COVID-19 vaccines (ChAdOx1 nCoV19 and LNP-nCoV RNA) when administered by aerosol in healthy adult volunteers. Each vaccine will be administered at 3 dose levels (in groups of 3 participants) with a further 6 individuals vaccinated with the highest tolerated dose. Systemic immunogenicity will be quantified using standardised assays for SARS-CoV-2 antibodies (by ELISA and virus neutralisation) and T cells (by IFN-g ELISpot). Serology will be performed in the same laboratory as the ongoing phase I/II/III trials of intramuscular ChAdOx1 nCov19, allowing direct data comparison. Additionally, all participants will undergo bronchoscopic sampling of the lower airway at pre-vaccination, day 21 and day 182 timepoints. Together with nasal specimens, these will be analysed for mucosal IgA, T cells by intracellular cytokine staining and flow cytometry, and soluble mediators by MesoScale Discovery using techniques aligned with previous human respiratory virus challenge studies.

Thus, we will provide proof-of-concept that these vaccines can safely induce specialised mucosal immune responses that may correlate with greater efficacy, accelerating the deployment of clinical trials to test their ability to prevent disease and transmission in the field.


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