A nose in front? Intranasal vaccines argue advantages over traditional injections

All currently licensed and approved COVID-19 vaccines are administered intramuscularly: but intranasal vaccine developers believe their format may have advantages over traditional vaccine administration, either as an initial vaccination regimen or as a reminder.

Needle Free Benefits

While intranasal vaccines may sound appealing thanks to needle-free delivery, the potential goes far beyond appealing to needle phobics.

Administration does not require a trained professional, sterile environment, syringe and needle; making self-administration possible and thus offering much wider distribution opportunities and greater adherence to vaccination.

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

There are currently nine intranasal COVID-19 vaccines in clinical development: which represents a lot of research in the field, but a small proportion of the approximately 150 COVID-19 vaccines in clinical trials (the vast majority of candidates naturally focus on the administration intramuscularly, but also represent other routes such as oral or subcutaneous administration).

Broad immune response

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

Current COVID-19 vaccines, administered intramuscularly, were designed to elicit systemic immunity. And yet it is the mucosal immunity of the nasal cavity that is the first line of defense against a virus transmitted by respiratory droplets: what intranasal vaccines promise to deliver along with systemic responses.

This was highlighted by Codagenix, headquartered in Farmingdale, NY, which is also considering Phase 2/3 trials for its live attenuated candidate COVI-VAC and announced in September promising safety and immunogenicity results in a phase 1 dose-escalation trial in healthy patients. adults.

“Our vaccine candidate appears capable of blocking surrogate replication of SARS-CoV-2 in the nose before it reaches the lower respiratory tract or lungs. This is likely achieved by stimulating both a systemic and mucosal immune response, emphasizing the value of a live, intranasal response. attenuated vaccine model,​ noted J. Robert Coleman, Ph.D., MBA, co-founder and CEO of Codagenix.

Additionally, Codagenix anticipates that its candidate could be produced and quickly scaled through existing manufacturing infrastructure.

Intranasal vaccines and transmission

Intramuscular vaccines still face questions about their effectiveness in reducing transmission. Intranasal vaccines, however, might be more effective in this area: with the potential to induce sterilizing immunity against mucosal pathogens.

In October, California-based 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 was built on the company’s AttenuBlock platform: already used for its intranasal RSV vaccine candidate.

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

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

The American Cynvac and its subsidiary Blue Lake Biotechnology also note the potential role of its candidates in blocking transmission: after launching a phase 1 trialfor its CVXGA1 intranasal vaccine (based on an attenuated strain of PIV5 (canine parainfluenza virus) and expressing the S protein of SARS-CoV-2) in September. In preclinical studies, the vaccine has been shown to induce mucosal antibody responses and cell-mediated immune responses as well as serum antibody responses, and has been shown to be effective in protecting several animal species against infection. transmission by SARS-CoV-2 and to block SARS-CoV-2 viral transmission.

Face to face: comparison of IM and IN vaccines

Perhaps one of the biggest questions is how intranasal vaccines compare to their intramuscular counterparts in terms of efficacy. The most telling data to date comes from the University of Oxford, which took the licensed vaccine from Oxford/AstraZeneca (ChAdOx1 nCoV-19) in an intranasal format.

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

The researchers also compared unvaccinated and intranasally vaccinated monkeys: they found that intranasally vaccinated monkeys exposed to SARS-CoV-2 had less virus in their nose and lung tissue than unvaccinated monkeys.

Today, the University of Oxford is conducting a Phase 1 clinical trial: testing the intranasal vaccine in 54 healthy adults between the ages of 18 and 55.

The study is looking at the vaccine in five different groups. The first three groups will cover people who have never been vaccinated with 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 consider the intranasal vaccine as a booster for those who have already been vaccinated with the same vaccine by the typical intramuscular route; while the fifth group will study recall in those who were initially vaccinated with Pfizer/BioNTech’s mRNA vaccine.

The 12-month trial is expected to last until May this year.