A nose ahead? Intranasal vaccines champion advantages over traditional injections

All currently authorized and approved COVID-19 vaccines are delivered intramuscularly: but intranasal vaccine developers believe their format can have advantages over traditional vaccine delivery, either as an initial vaccination regimen or as a booster. 

Needle-free advantages

While intranasal vaccines may sound attractive thanks needle-free delivery, the potential goes far beyond an appeal to the needle-phobic.

Administration does not require a trained professional, sterile environment, and syringe and needle; making self-administration possible and thus offering much broader possibilities of distribution and a greater uptake in vaccination.

And intranasal vaccines hope to stop the virus in its tracks at its point of entry: focusing on the immune response in the nose.

There are currently nine intranasal COVID-19 vaccines in clinical development: representing plenty of research in the area but a small proportion of the 150 or so COVID-19 vaccines in clinical trials (the vast majority of candidates are naturally focused on intramuscular administration, but also represent other routes such as oral or subcutaneous administration).

Broad immune response

One of the more advanced is a candidate from Bharat Biotech: with the Indian vaccine developer prepping to take the novel adenovirus vectored, intranasal COVID-19 vaccine into Phase 3 trials​​, claiming a broad immune response by neutralizing IgG, muscosal IgA, and T cell responses.

Current COVID-19 vaccines, delivered intramuscularly, have been designed to elicit systemic immunity. And yet it is mucosal immunity in the nasal compartment which is the first line of defense against a virus spread by respiratory droplets: which intranasal vaccines pledge to deliver alongside systemic responses.​​

This has been highlighted y Farmingdale, New York-headquartered Codagenix: which is also looking at Phase 2/3 trials for its live-attenuated candidate COVI-VAC and in September announced promising safety and immunogenicity results in a Phase 1 dose escalation trial in healthy adults.

"Our vaccine candidate appears able to block surrogate SARS-CoV-2 replication in the nose before it reaches the lower airways or lungs. This is likely achieved by stimulating both a systemic and mucosal immune response, highlighting the value of an intranasal, live-attenuated vaccine model,”​ noted J. Robert Coleman, Ph.D., M.B.A., co-founder and CEO of Codagenix.

Furthermore, Codagenix anticipates that its candidate could be produced and rapidly scaled up via existing manufacturing infrastructure.

Intranasal vaccines and transmission

Intramuscular vaccines still face questions on how effective they are in reducing transmission. Intranasal vaccines, however, could be more effective in this area: with the potential to induce sterilizing immunity against mucosal pathogens.

In October, Californian biotech Meissa Vaccines revealed preliminary data from an interim analysis of 49 patients in a Phase 1 trial for MV-014,212, the company’s intranasal recombinant live attenuated COVID-19 vaccine. The vaccine has been build on the company’s AttenuBlock platform: already used for its intranasal RSV vaccine candidate.

The interim results suggested the vaccine could stimulate a nasal IgA antibody response similar to that seen after SARS-CoV-2 infection.

“While circulating IgG antibodies are important for preventing serious lung disease, nasal IgA antibodies are essential for blocking infection and transmission of respiratory viruses. Injectable vaccines typically induce only serum (IgG) antibodies that circulate in the blood, whereas intranasal vaccines also generate mucosal (IgA) antibodies in the nasal cavity.”​

The US’ Cynvac and its subsidiary Blue Lake Biotechnology also notes its candidates potential role in blocking transmission: having started a phase 1 trial​​ for its CVXGA1 intranasal vaccine (based on an attenuated strain of PIV5 (canine parainfluenza virus) and expresses the S protein of SARS-CoV-2) in September. In preclinical studies the vaccine was shown to induce mucosal antibody responses and cell-mediated immune responses as well as serum antibody responses, and was shown to be be effective in protecting multiple animal species from SARS-CoV-2 viral infection and in blocking SARS-CoV-2 viral transmission.

Head to head: comparing IM and IN vaccines

Perhaps one of the biggest questions is how intranasal vaccines stack up compared to their intramuscular counterparts in terms of efficacy. The most telling data so far comes from the University of Oxford, which has taken the authorized Oxford/AstraZeneca vaccine (ChAdOx1 nCoV-19) into an intranasal format.

In a study published in Science Translational Medicine​ in July, researchers compared the intramuscular and intranasal format administered in hamsters. Both routes of administration produced high levels of antibodies against SARS-CoV-2 in the blood after a single dose. Levels of antibodies in the blood were actually higher after intranasal administration.​​

The researchers also compared unvaccinated and intranasally vaccinated monkeys: finding that the intranasally vaccinated monkeys exposed to SARS-CoV-2 had less virus in their noses and lung tissue compared to the unvaccinated monkeys.

Now, the University of Oxford is running a Phase 1 clinical trial: testing the intranasal vaccine in 54 healthy adults aged 18-55 years old.

The study is looking at the vaccine across five different groups. The first three groups will cover vaccine naïve individuals with either one or two doses. The doses will cover three different levels: a standard dose equivalent to that given by injection, plus two lower doses.

The fourth group will look at the intranasal vaccine as a booster for those who have already been vaccinated with the same vaccine via the typical intramuscular route; while the fifth group will investigate the booster in those who were initially vaccinated with Pfizer/BioNTech’s mRNA vaccine.  

The 12 month trial is set to run until May this year.