All approved COVID-19 vaccines so far are administered in the form of injections. What if the vaccines could be conveniently delivered as spray in the nose? If you do not like shots, here may be the good news! Intranasal administration of COVID-19 vaccine through spray could soon be a reality. Currently, many companies are researching on exploiting the nasal route of administration for COVID-19 vaccines, some of which are undergoing clinical trials. This article discusses the progress made in this regard with particular emphasis on the use of attenuated viruses in a nasal spray formulation against COVID-19.
The emergence of COVID-19 as a pandemic triggered frantic research all over the world to combat this pandemic by developing vaccines in a race against time in order to help countries all over the world to return to normalcy as soon as possible. A number of pharmaceutical and biotech companies have been engaged in vaccine development and till date over 300 vaccine projects have been initiated and more than 40 projects are in clinical evaluation while at least 5 of them have been approved as an emergency use authorization in different countries. Vaccines have been made using different approaches such as live attenuate vaccine, mRNA-based vaccine that expresses the Spike protein of the virus as well as Adenovirus based vaccine that expresses several proteins of the virus. All these proteins are expressed by the host and in turn mount an antibody response to the viral proteins thereby providing protection.
An alternative mode of preventing viral entry into the human body and delivering a vaccine candidate is to use the nasal route. Several researchers have used nasal spray1 consisting of sticky substances that coat the nasal mucus lining, thereby preventing the viral entry into the hosts cells. For example, use of nanoconjugate as nasal spray to deliver the shRNA-plasmid to the target site 2. Intranasal route for administration of COVID-19 vaccine has been investigated by many researchers 3. There are several companies in the fore-front in the use of nasal spray technique for administering of vaccines against COVID-19. A few of these companies use the attenuated virus, while others are using the adenovirus based or influenza-based vectors in the form of nasal spray 4.
The companies that are exploiting the adenovirus, influenza-based virus and Newcastle disease virus (NDV)5, 6 based vectors in a nasal spray formulation include Beijing Antai Biol Pharm Enterprise, China, two projects from Acad Mil Sci, China, Bharat Biotech-Washington Univ, India-US, AstraZeneca, Sweden-UK, Altimmune, USA, Univ Hong Kong, Valavax-Abogn, China, Beijin Vantal Biol Pharm, China and Lancaster University, UK. On the other hand, companies that are utilizing attenuated virus in a nasal spray formulation include Codagenix, a New York based company in collaboration with The Serum Inst of India, India, Indian Immunologicals Ltd, India, in collaboration with the Griffith University, Australia and Mehmet Ali Aydunar Univ, Turkey. Of particular interest are the companies that are using the attenuated whole virus in a nasal spray formulation as the whole virus will retain the capability of mounting an immune response to the varied antigens present in the virus as opposed to only certain proteins being targeted for antibody production as is the case with adenovirus based, influenza-based and Newcastle disease virus-based vaccines. This may potentially take care of the several mutations the virus in undergoing as well. In this article, we will specifically focus on the development and trials for the nasal spray vaccine that use the attenuated virus.
The first group that uses attenuated virus in a nasal spray are researchers at Codagenix, USA whose vaccine is named COVI-VAC. The first patient in the randomised, double-blinded, placebo-controlled trial has been dosed in January 2021. They have entered into collaboration with The Serum Institute of India for the manufacture of this vaccine. The dose-escalation study has been designed to evaluate the safety and tolerability of the vaccine in a total of 48 healthy volunteers. The study will also assess the ability of the vaccine to generate an immune response which will be assessed by measuring neutralising antibodies, mucosal immunity in the airway and cellular immunity. The vaccine can be stored easily in a refrigerator (2-8 C), can be administered easily without the help of skilled personnel and is hopefully available as a single dose that can afford protection. This alleviates the need for storage and transportation at sub-zero temperatures and can be readily given to a large number of people at a time without the need for additional equipment and skilled personnel 7.
Another group at Eureka Therapeutics has developed InvisiMask™ , a Human Antibody Nasal Spray which has been successfully tested in preclinical studies in mice without any significant adverse effects. The human monoclonal antibody binds to the S1 Spike (S) protein of SARS-CoV-2 virus and prevent them from binding to the angiotensin-converting enzyme 2 (ACE2) receptor on cells in the upper respiratory tract. This prevents the virus from entering into human cells and thereby prevents infection. Another key feature of this vaccine is that the human monoclonal antibody used can bind and inhibit more than 20 SARS-CoV-2 variants, including the highly infectious D614G mutation 8,9.
These vaccines based on intra nasal spray route provide an excellent non-invasive way of administering vaccines against SARS-CoV-2 virus and can be of great help in controlling the COVID-19 pandemic. There are several advantages of using the nasal spray route for administering the vaccine. Nasal spray vaccine provides additional local protection at the site of administration (mucosal immunity based on secretory IgA and IgM and as a physical barrier) in addition to the systemic protection, in comparison to injected vaccine that confers only systemic protection. People administered with intra muscular vaccines can still have COVID-19 virus in their nasal cavity and can transmit it to others.
- Cavalcanti, I.D.L., Cajubá de Britto Lira Nogueira, M. Pharmaceutical nanotechnology: which products are been designed against COVID-19?. J Nanopart Res 22, 276 (2020). https://doi.org/10.1007/s11051-020-05010-6
- Prospective vaccination of COVID-19 using shRNA-plasmid-LDH nanoconjugate https://doi.org/10.1016/j.mehy.2020.110084
- Pollet J., Chen W., and Strych U., 2021. Recombinant protein vaccines, a proven approach against coronavirus pandemics. Advanced Drug Delivery Reviews. Volume 170, March 2021, Pages 71-82. DOI: https://doi.org/10.1016/j.addr.2021.01.001
- Forni, G., Mantovani, A., on behalf of the COVID-19 Commission of Accademia Nazionale dei Lincei, Rome. et al. COVID-19 vaccines: where we stand and challenges ahead. Cell Death Differ 28, 626–639 (2021). Published: 21 January 2021. DOI: https://doi.org/10.1038/s41418-020-00720-9
- University of Birmingham 2020. News – Anti-COVID-19 nasal spray ‘ready for use in humans’. Posted on 19 Nov 2020. Available online at https://www.birmingham.ac.uk/news/latest/2020/11/anti-covid-19-nasal-spray-ready-for-use-in-humans.aspx
- Park J, Oladunni FS., et al 2021. Immunogenicity and Protective Efficacy of an Intranasal Live-attenuated Vaccine Against SARS-CoV-2 in Preclinical Animal Models. Posted January 11, 2021. doi: https://doi.org/10.1101/2021.01.08.425974
- ClinicalTrial.gov 2020. Safety and Immunogenicity of COVI-VAC, a Live Attenuated Vaccine Against COVID-19. ClinicalTrials.gov Identifier: NCT04619628. Available online at https://clinicaltrials.gov/ct2/show/NCT04619628?term=COVI-VAC&cond=Covid19&draw=2&rank=1
- Eureka Therapeutics, Inc. 2020. Press Release – Eureka Therapeutics Announces Successful Preclinical Results of Invisimask™ Human Antibody Nasal Spray Against Sars-cov-2 Infection. Posted 14 December 2020 Available from: https://www.eurekatherapeutics.com/media/press-releases/121420/
- Zhang H., Yang Z., et al 2020. Intranasal administration of SARS-CoV-2 neutralizing human antibody prevents infection in mice. Preprint bioRxiv . Posted 09 December 2020. DOI: https://doi.org/10.1101/2020.12.08.416677