In a recent study published in Nature Immunology, a team of researchers from the United States used non-human primate models to compare the protection conferred by an intramuscular booster dose of the bivalent messenger ribonucleic acid (mRNA) coronavirus disease 2019 (COVID-19) vaccine with that provided by a booster dose of a mucosal bivalent adenoviral vector vaccine delivered through an aerosol device or intranasal route.
Background
The rapidly developed COVID-19 vaccines were successful in limiting the severity and transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections, and the intramuscular booster doses continue to confer protection against high levels of morbidity and hospitalization.
However, studies have shown that the efficacy of intramuscularly administered bivalent mRNA vaccines vane after approximately four months, while breakthrough SARS-CoV-2 infections continue to occur.
Factors such as age, immunocompromised conditions, and post-acute sequelae could influence innate immunity levels and vaccine response, increasing the probability of breakthrough infections.
Vaccines that can prevent breakthrough infections would be effective in lowering the transmission levels and preventing the emergence of novel SARS-CoV-2 variants.
A mucosal vaccine, administered intranasally, could limit the transmission of SARS-CoV-2 by boosting the plasma cells and memory B cells in the lymphoid tissue associated with the mucosa and increasing the immune responses at the site of the infection.
About the study
In the present study, the researchers used Macaca mulatta or rhesus macaques to investigate the protective immune responses elicited by a mucosal bivalent adenoviral vector vaccine containing stabilized spike protein from the ancestral Wuhan strain and the Omicron BA.5 variant of SARS-CoV-2.
They compared these immune responses against those elicited by an intramuscular booster dose of a bivalent mRNA vaccine encoding the spike proteins of the same two variants.
Although the inflammation and pathology due to severe disease in humans are not completely recapitulated in non-human primate models, studies have shown that the virus readouts and immune responses observed in non-human primate models can be used to predict the clinical outcomes for Omicron infections in humans.
The adenoviral vector vaccine used in the study was the ChAd-SARS-CoV-2-S vaccine, which is currently being administered in the form of nasal drops in India under the name iNCOVACC. Viral vector vaccines using adenovirus, Newcastle disease virus, or parainfluenza virus can elicit immune responses at the site of the infection, making these vaccines an ideal candidate for a mucosal, intranasally administered booster dose.
The rhesus macaques in the study were primed with two intramuscular doses of an mRNA vaccine encoding the spike protein from the ancestral Wuhan strain.
Seven months after they were primed, one group of macaques was administered with the bivalent ChAd-SARS-CoV-2-S vaccine through an aerosol device, and the vaccine was delivered to the lower and upper airways.
A second group was administered the vaccine intranasally in the form of a mist using a clinical sprayer. In contrast, a comparison group was intramuscularly administered a booster dose of the bivalent mRNA vaccine.
The protection conferred by the mucosal adenoviral vector vaccine administered through aerosol and intranasal routes and the intramuscular booster dose of the bivalent mRNA vaccine were compared by challenging the animals with the XBB.1.16 strain of the virus four and a half months after the booster doses were administered.
Results
The study found that the viral replication in the lungs and the nose of the animals that were administered the mucosal adenoviral vector vaccine against SARS-CoV-2 was minimal for the animals in both the aerosol and intranasal administration groups.
In contrast, the animals that were intramuscularly administered the booster dose of the bivalent mRNA vaccine showed lower levels of viral replication only in the lower airways.
The mucosal vaccine also resulted in durable immunoglobulin (Ig) A and IgG responses in the airways and activated B cells specific for the spike protein in the lungs, which was not observed in the case of the intramuscular bivalent mRNA vaccine booster dose.
The study found that the aerosolized delivery of the mucosal vaccine elicited broad mucosal immunity in multiple respiratory compartments, which could rapidly suppress the replication of SARS-CoV-2.
In comparison, the intranasally administered booster dose of the same vaccine could only boost the IgA titers in the airway, which could prevent the local replication of the virus but could not inhibit viral replication in the lungs as effectively as the aerosolized booster dose or elicit memory B cells specific to the spike protein.
Conclusions
Overall, the findings showed that a booster dose of mucosal adenoviral vector vaccine against SARS-CoV-2, administered as an aerosol, was most effective in controlling viral replication in the lungs and the nose.
The IgA titers in the airways were indicative of the protection in the upper respiratory compartments. In contrast, memory B cell and T cell responses, as well as IgA and IgG titers, correlated with the protection conferred in the lower airways.
- Gagne, M., Flynn, B.J., Andrew, S.F., Marquez, J., Flebbe, D.R., Mychalowych, A., Lamb, E., DavisGardner, M.E., Burnett, M.R., Serebryannyy, Leonid A, Lin, B.C., Ziff, Z.E., Maule, E., Carroll, R., Naisan, M., Jethmalani, Y., Pessaint, L., Todd, J.M., DoriaRose, N.A. & Case, J.B. (2024). Mucosal adenovirus vaccine boosting elicits IgA and durably prevents XBB.1.16 infection in nonhuman primates. Nature Immunology. doi:10.1038/s41590024019515. https://www.nature.com/articles/s41590-024-01951-5

News
Small antibodies provide broad protection against SARS coronaviruses
Scientists have discovered a unique class of small antibodies that are strongly protective against a wide range of SARS coronaviruses, including SARS-CoV-1 and numerous early and recent SARS-CoV-2 variants. The unique antibodies target an [...]
Controlling This One Molecule Could Halt Alzheimer’s in Its Tracks
New research identifies the immune molecule STING as a driver of brain damage in Alzheimer’s. A new approach to Alzheimer’s disease has led to an exciting discovery that could help stop the devastating cognitive decline [...]
Cyborg tadpoles are helping us learn how brain development starts
How does our brain, which is capable of generating complex thoughts, actions and even self-reflection, grow out of essentially nothing? An experiment in tadpoles, in which an electronic implant was incorporated into a precursor [...]
Prime Editing: The Next Frontier in Genetic Medicine
By Dr. Chinta SidharthanReviewed by Benedette Cuffari, M.Sc. Discover how prime editing is redefining the future of medicine by offering highly precise, safe, and versatile DNA corrections, bringing hope for more effective treatments for genetic diseases [...]
Can scientists predict life longevity from a drop of blood?
Discover how a new epigenetic clock measures how fast you are really aging from just a drop of blood or saliva. A recent study published in the journal Nature Aging constructed an intrinsic capacity (IC) clock [...]
What is different about the NB.1.8.1 Covid variant?
For many of us, Covid-19 feels like a chapter we’ve closed – along with the days of PCR tests, mask mandates and daily case updates. But while life may feel back to normal, the [...]
Scientists discover single cell creatures can learn new behaviours
It was previously thought that learning behaviours only applied to animals with complex brain and nervous systems, but a new study has proven that this may also occur in individual cells. As a result, this new evidence may change how [...]
Virus which ’causes multiple organ failure’ found at popular Spanish holiday destination
British tourists planning trips to Spain have been warned after a deadly virus that can cause multiple organ failure has been detected in the country. The Foreign Office issued the alert on its dedicated website Travel [...]
Urgent health warning as dangerous new Covid virus from China triggers US outbreak
A dangerous new Covid variant from China is surging in California, health officials warn. The California Department of Public Health warned this week the highly contagious NB.1.8.1 strain has been detected in the state, making it the [...]
How the evolution of a single gene allowed the plague to adapt, prolonging the pandemics
Scientists have documented the way a single gene in the bacterium that causes bubonic plague, Yersinia pestis, allowed it to survive hundreds of years by adjusting its virulence and the length of time it [...]
Inhalable Nanovaccines: The Future of Needle-Free Immunization
The COVID-19 pandemic highlighted the need for adaptable and scalable vaccine technologies. While mRNA vaccines have improved disease prevention, most are delivered by intramuscular injection, which may not effectively prevent infections that begin at [...]
‘Stealthy’ lipid nanoparticles give mRNA vaccines a makeover
A new material developed at Cornell University could significantly improve the delivery and effectiveness of mRNA vaccines by replacing a commonly used ingredient that may trigger unwanted immune responses in some people. Thanks to [...]
You could be inhaling nearly 70,000 plastic particles annually, what it means for your health
Invisible plastics in the air are infiltrating our bodies and cities. Scientists reveal the urgent health dangers and outline bold solutions for a cleaner, safer future. In a recent review article published in the [...]
Experts explain how H5 avian influenza adapts to infect more animals
A new global review reveals how rapidly evolving H5 bird flu viruses are reaching new species, including dairy cattle, and stresses the urgent need for coordinated action to prevent the next pandemic. Since its [...]
3D-printed device enables precise modeling of complex human tissues in the lab
A new, easily adopted, 3D-printed device will enable scientists to create models of human tissue with even greater control and complexity. An interdisciplinary group of researchers at the University of Washington and UW Medicine [...]
Ancient DNA sheds light on evolution of relapsing fever bacteria
Researchers at the Francis Crick Institute and UCL have analyzed ancient DNA from Borrelia recurrentis, a type of bacteria that causes relapsing fever, pinpointing when it evolved to spread through lice rather than ticks, and [...]