An interesting review published by Alu and others in the Lancet February 1st 2022 tries to summarise this issue. 

Currently licensed COVID-19 vaccines are all designed for intramuscular immunisation.  

However, vaccination today failed to prevent the virus infection through the upper respiratory tract, which is partially due to the absence of mucosal immunity activation.

Despite the emerging SARS-CoV-2 variants, the next generation of COVID-19 vaccine is in demand and intranasal vaccination method has been demonstrated to be potent in inducing both mucosal and systemic immune responses.  

Presently, although not licensed, various intranasal vaccines against SARS-CoV-2 are under intensive investigation, with 12 candidates reaching clinical trials at different phases.  

All the licensed COVID-19 vaccines are administered via intramuscular injection, which are ineffective in inducing mucosal immunity.  

Alternatively, mucosal immunisation has the potential to reduce both mucosal and systemic immune responses.  Nine mucosal vaccines have been approved for humans against various mucosal pathogens, including eight orally and one intranasally administered vaccines, all of which belong to whole virus vaccines.  

Intranasal vaccines are highly attractive without the requirement of needles.  The significant advances of subunit protein vaccines and virus-vectored vaccines have been translated into intranasal vaccines for SARS-CoV-2 in the preclinical and clinical setting.

Intranasal vaccine is a promising preventative strategy for SARS-CoV-2 considering the remarkable protective immunity in the mucosal sites.  The investigation of intranasal COVID-19 vaccines predominantly focused on safer vaccine platforms, especially viral vectors and protein subunits.  Nevertheless, the poor immunogenicity and stability of highly pure subunit antigens require the application of mucosal adjuvant delivery systems to overcome the harsh mucosal barriers and enhance immune responses.  

Avoiding nasal clearing is one of the biggest challenges in the development of intranasal vaccines.  

Current studies have demonstrated that intranasal immunisation with different types of COVID-19 vaccines induced robust protective immunity in animal models.  These promising results tremendously promote their evaluation in clinical trials.  

However, it is still not known about how the mucosal and systemic immune responses are triggered by intranasal immunisation with various vaccines.  

Furthermore, tremendous efforts are necessary to develop desirable mucosal adjuvants and delivery systems with high effectivity and tolerability to efficiently deliver the intact forms of antigens towards target cells.  

Finally, there may be ethical considerations of immunisation with intranasal

COVID-19 vaccines without intramuscular protection.  Since intranasal vaccines exhibit plenty of advantages over intramuscular vaccines, we should popularise the public about intranasal vaccines’ features and immune mechanisms and offer the general public a choice of the immunisation methods.  

Intranasal immunisation routes can induce sterilising mucosal and systemic immunity, and further prevent virus infection and transmission.  Application of intranasal vaccines will hopefully help deal with the persistent
COVID-19 pandemic and potentially viral contagious diseases in the future.

To further optimise the potential values of intranasal vaccines of SARS-CoV-2 and promote their translation into clinic, there remains much to be done, including:

  1. Precise mechanisms of how intranasal vaccines activate the mucosal and systemic immune responses need to be clarified.
  2. Ensure the efficacy of intranasal vaccines and whether they are adoptable to scale-up strategies. 
  3. Develop ideal mucosal adjuvants and delivery systems that can guarantee the efficacy and safety of intranasal vaccines at the same time.  

The London General Practice, the leading doctors’ clinic in Harley Street commends the National Health Service on its vaccination programme and encourages all those eligible to be vaccinated.

Dr Paul Ettlinger

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