Oral and intranasal COVID-19 vaccines show promising results in hamster model

A new preprint discusses the protective effect of an oral adenovirus-vectored vaccine based on the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike against viral transmission and disease in hamsters.

Study: Oral and intranasal Ad5 SARS-CoV-2 vaccines decrease disease and viral transmission in a golden hamster model. Image Credit: PalSand/ ShutterstockStudy: Oral and intranasal Ad5 SARS-CoV-2 vaccines decrease disease and viral transmission in a golden hamster model. Image Credit: PalSand/ Shutterstock

A preprint version of the study is available on the bioRxiv* server while the article undergoes peer review.


SARS-CoV-2 gains entry through the nasal mucosa before entering the lungs and other organs. Mucosal immunity could thus be the most effective at controlling the viral spread.

At present, safe and effective vaccines are administered by intramuscular injection to prevent symptomatic infection with SARS-CoV-2. Transmission still occurs in part, however, and breakthrough infections have been repeatedly reported in vaccinated people.

People who have received two doses of a vaccine, such as those produced by Pfizer/BioNTech or Moderna, have been shown to shed viral RNA and infectious viral particles, thus spreading the virus to others. With most of the world’s people remaining unimmunized at present, a breakthrough infection in a vaccinated individual can probably pass on to an unimmunized person in the family or community.

There is thus a pressing need for vaccines that can end viral transmission, thus preventing both disease and viral spread from those who are vaccinated to the unvaccinated proportion of the population.

What did the study show?

The current study reports a shelf-stable oral vaccine that has been engineered to prevent replication of the adenovirus vector while expressing SARS-CoV-2 spike protein in the host cell.

The route of administration ensures that the vaccine can elicit local and systemic immunity. The oral vaccine may reach the gut and stimulate antibody formation. The plasmablasts and plasma cells from the gut may travel to the upper respiratory tract, namely, the nose, the trachea, and the lungs.

The current study was based on hamsters vaccinated with an oral vaccine, comparing with three control groups: those that received either intranasal adenovirus-SARS-CoV-2 spike or intramuscular spike protein, or placebo by mouth. These controls served to compare the extent of mucosal stimulation, systemic stimulation, and placebo, respectively.

Post-vaccination, the animals were challenged intranasally with a high titer of SARS-CoV-2. From the next day, they were allowed to be in the same chamber with unvaccinated hamsters, though upstream of the latter, and never in contact with them directly or through their fomites.

The researchers found that when the candidate vaccine was used either orally or intranasally in hamsters, the animals were protected against disease. At the same time, there was a decrease in aerosol transmission to unvaccinated hamsters. Mucosal vaccines thus produced a strong antibody response.

The vaccinated animals, both oral and intranasal groups, showed increased serum antibody titers, both immunoglobulin (Ig)G and IgA levels than controls, and higher IgA in the lung fluid washings. Viral RNA and infectious particles were reduced in the upper respiratory tract, and the animals did not lose as much weight or develop lung lesions.

The transmission was assessed by allowing naïve hamsters to be exposed to the air flowing in one direction from hamsters that had received the mucosal vaccine. The naïve hamsters had lower viral RNA loads in the nose and fewer symptomatic animals.

The unvaccinated hamsters were protected against aerosol transmission from the vaccinated animals. They showed less lung inflammation and weight loss, even though the vaccinated animals upstream of them had detectable viral RNA in the nasal swabs. The oral vaccine thus reduced both disease and transmission in hamsters.

The vaccinated animals also showed a higher viral clearance rate when infected with a high dose of the virus. At the same time, transmission via aerosol was significantly reduced, with low viral RNA loads in the naïve animals on day one and day three from exposure. This suggests that mucosal antibodies were elicited in the upper respiratory tract and were responsible for these effects.

Anti-spike IgA levels in animals who received intranasal and oral vaccines exceeded those of both intramuscular and placebo groups. These findings, along with those of earlier studies, show that intranasal and oral vaccination blocked transmission from either vaccinated and unvaccinated animals inoculated with SARS-CoV-2 to both vaccinated or naïve animals.

What are the implications?

This is the first demonstration that “mucosal vaccination can reduce SARS-CoV-2 transmission from vaccinated to unvaccinated animals.”

The benefits of vaccination appeared in the reduction in viral RNA and infectious viral particles in the nose and the lungs. Lung lesions were also markedly reduced in the vaccinated hamsters compared to controls.

The study did not assess mucosal T cell responses, and the infective dose used was supra-physiological, much more than normally encountered in real-life settings. Instead, it was intended to confirm the benefit of the mucosal vaccine.

Further work will be required to evaluate how these vaccines work against the Delta variant. If found to be equally effective, the implications are enormous.

*Important notice

bioRxiv publishes preliminary scientific reports that are not peer-reviewed and, therefore, should not be regarded as conclusive, guide clinical practice/health-related behavior, or treated as established information.

Journal reference:
Dr. Liji Thomas

Written by

Dr. Liji Thomas

Dr. Liji Thomas is an OB-GYN, who graduated from the Government Medical College, University of Calicut, Kerala, in 2001. Liji practiced as a full-time consultant in obstetrics/gynecology in a private hospital for a few years following her graduation. She has counseled hundreds of patients facing issues from pregnancy-related problems and infertility, and has been in charge of over 2,000 deliveries, striving always to achieve a normal delivery rather than operative.


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