Development of Intranasal Covid-19 Vaccines in US

“The first generation of vaccines are probably going to protect a lot of people,” said Michael Diamond, an infectious disease specialist at Washington University in St. Louis. “But I think it’s the second- and third-generation vaccines — and maybe intranasal vaccines will be a key component of blocking transmission— that ultimately are going to be necessary. Otherwise, we’ll continue to have community transmission.”

Of the vaccines currently in Phase 3 trials, all are administered by injection, according to the World Health Organization (WHO).

But, based on a news from Reuters, it reported on 10/18/2020 that:

Serum Institute of India and Bharat Biotech are expected to pursue late stage clinical trials of intranasal COVID-19 vaccines in the coming months once they receive regulatory approval, Health Minister Dr. Harsh Vardhan said on Sunday.

Potential Benefits of Intranasal vaccines

Inhaled and nasal vaccine makers are counting on some of the unique features of the lungs, nose and throat, which are lined with mucosa. This tissue contains high levels of immune proteins, called IgA, that give better protection against respiratory viruses. Note that the amount of IgA produced in association with mucosal membranes is greater than all other types of antibody combined.

Antibodies secreted at the mucosal surface play an integral role in immune defense by serving to neutralize the pathogen and promote its elimination at the site of entry.

In [21], it demonstrates that:

Intranasal, but not systemic, immunization induces local IgA secretion in the bronchoalveolar space.

In Summary, intranasal vaccines may hold the below benefits:

• May offer ease of self administration
  • Don’t require needles
  • Can reduce the need for health workers to administer them
• May not need to be stored and shipped at low temperatures
• May improve vaccines’ chances of blocking Covid transmission
• The nasal route of administration mimics the natural route of infection by coronavirus and influenza and can activate both mucosal and systemic immunity
• May protect areas deeper in the lungs where the SARS-CoV-2 does the most damage
• May induce local IgA secretion in the lower respiratory tract^[21]

Considerations on Device Selection

Both liquid and dry powder formulations can be given via intranasal route. A great consideration has to be given while selecting a suitable device for nasal administration since the volume delivered is very low. A number of devices are available based on number of doses to be administered and type of dosage formulation.

Developments in US

AdCOVID (Based on a report on 10/22/2020)

Altimmune announced a preclinical evaluation of its single-dose, intranasal vaccine candidate, AdCOVID. The pre-clinical studies were conducted as part of Altimmune’s ongoing collaboration with the University of Alabama at Birmingham. These researchers stated 'AdCOVID, which promotes concomitant systemic and local mucosal immunity, represents a promising COVID-19 vaccine candidate.'

Based on the positive outcomes of the preclinical study, the Company plans to advance the vaccine candidate to a Phase 1 safety and immunogenicity study in Q4 of 2020.

CoroFlu (Based on a report on 04/02/2020)

CoroFlu, a unique intranasal vaccine against COVID-19, is under development by an international collaboration of virologists at the University of Wisconsin–Madison and the vaccine companies FluGen and Bharat Biotech. Refinement of the CoroFlu vaccine concept and testing in animal models at UW–Madison is expected to take 3-6 months. Bharat Biotech in Hyderabad, India will then begin production scale-up for safety and efficacy testing in humans. CoroFlu could be in human clinical trials by the fall of 2020.

CoroFlu builds on the backbone of FluGen’s flu vaccine candidate known as M2SR. The group will insert gene sequences from SARS-CoV-2, the novel coronavirus that causes the disease COVID-19, into M2SR so that the new vaccine will also induce immunity.

References

1. Gilead’s coronavirus drug: why experts are cautious on its prospects (ft.com)
2. A COVID-19 vaccine: 5 things that could go wrong
3. Covid-19 vaccine delivery faces problems, warns DHL
4. Moderna COVID-19 vaccine appears to work as well in older adults in early study
• Moderna said the immune responses in those aged between ages 56 and 70, above age 70 and those 18 to 55-years-old were similar
• Moderna has never brought a vaccine to market before
5. Iceland Has Very Good News About Coronavirus Immunity
6. Inhaled Vaccines Aim to Fight Coronavirus at Its Point of Attack
7. COVID-19 antibodies last at least three months; so do symptoms for many
8. Eli Lilly Virus Antibody Trial Paused Due to Safety Concerns
9. Characterizing COVID-19 antibodies for potential treatments
10. Why and How Vaccines Work
11. Serum Institute, Bharat Biotech to begin trial of intranasal COVID-19 vaccine soon: Vardhan
12. INHALED AND NASAL COVID-19 VACCINE PROGRESS
13. Advantages of Intranasal Vaccination and Considerations on Device Selection
14. Anti-COVID-19 nasal spray 'ready for use in humans'
15. Mucosal Immunity in COVID-19: A Neglected but Critical Aspect of SARS-CoV-2 Infection
16. Safety and Immunogenicity of an Intranasal SARS-CoV-2 Vaccine (BBV154) for COVID-19
17. Safety and Immunogenicity of AdCOVID in Healthy Adults (COVID-19 Vaccine Study)
18. BBV154 - A novel adenovirus vectored, intranasal vaccine for COVID-19
19. Updates on eliciting mucosal immunity for protection against SARS-CoV-2 (Tweeter thread)
20. Efficient mucosal antibody response to SARS-CoV-2 vaccination is induced in previously infected individuals
21. Intranasal priming induces local lung-resident B cell populations that secrete protective mucosal antiviral IgA