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
New study suggests a way to rejuvenate the immune system
Stimulating the liver to produce some of the signals of the thymus can reverse age-related declines in T-cell populations and enhance response to vaccination. As people age, their immune system function declines. T cell [...]
Nerve Damage Can Disrupt Immunity Across the Entire Body
A single nerve injury can quietly reshape the immune system across the entire body. Preclinical research from McGill University suggests that nerve injuries may lead to long-lasting changes in the immune system, and these [...]
Fake Science Is Growing Faster Than Legitimate Research, New Study Warns
New research reveals organized networks linking paper mills, intermediaries, and compromised academic journals Organized scientific fraud is becoming increasingly common, ranging from fabricated research to the buying and selling of authorship and citations, according [...]
Scientists Unlock a New Way to Hear the Brain’s Hidden Language
Scientists can finally hear the brain’s quietest messages—unlocking the hidden code behind how neurons think, decide, and remember. Scientists have created a new protein that can capture the incoming chemical signals received by brain [...]
Does being infected or vaccinated first influence COVID-19 immunity?
A new study analyzing the immune response to COVID-19 in a Catalan cohort of health workers sheds light on an important question: does it matter whether a person was first infected or first vaccinated? [...]
We May Never Know if AI Is Conscious, Says Cambridge Philosopher
As claims about conscious AI grow louder, a Cambridge philosopher argues that we lack the evidence to know whether machines can truly be conscious, let alone morally significant. A philosopher at the University of [...]
AI Helped Scientists Stop a Virus With One Tiny Change
Using AI, researchers identified one tiny molecular interaction that viruses need to infect cells. Disrupting it stopped the virus before infection could begin. Washington State University scientists have uncovered a method to interfere with a key [...]
Deadly Hospital Fungus May Finally Have a Weakness
A deadly, drug-resistant hospital fungus may finally have a weakness—and scientists think they’ve found it. Researchers have identified a genetic process that could open the door to new treatments for a dangerous fungal infection [...]
Fever-Proof Bird Flu Variant Could Fuel the Next Pandemic
Bird flu viruses present a significant risk to humans because they can continue replicating at temperatures higher than a typical fever. Fever is one of the body’s main tools for slowing or stopping viral [...]
What could the future of nanoscience look like?
Society has a lot to thank for nanoscience. From improved health monitoring to reducing the size of electronics, scientists’ ability to delve deeper and better understand chemistry at the nanoscale has opened up numerous [...]
Scientists Melt Cancer’s Hidden “Power Hubs” and Stop Tumor Growth
Researchers discovered that in a rare kidney cancer, RNA builds droplet-like hubs that act as growth control centers inside tumor cells. By engineering a molecular switch to dissolve these hubs, they were able to halt cancer [...]
Platelet-inspired nanoparticles could improve treatment of inflammatory diseases
Scientists have developed platelet-inspired nanoparticles that deliver anti-inflammatory drugs directly to brain-computer interface implants, doubling their effectiveness. Scientists have found a way to improve the performance of brain-computer interface (BCI) electrodes by delivering anti-inflammatory drugs directly [...]
After 150 years, a new chapter in cancer therapy is finally beginning
For decades, researchers have been looking for ways to destroy cancer cells in a targeted manner without further weakening the body. But for many patients whose immune system is severely impaired by chemotherapy or radiation, [...]
Older chemical libraries show promise for fighting resistant strains of COVID-19 virus
SARS‑CoV‑2, the virus that causes COVID-19, continues to mutate, with some newer strains becoming less responsive to current antiviral treatments like Paxlovid. Now, University of California San Diego scientists and an international team of [...]
Lower doses of immunotherapy for skin cancer give better results, study suggests
According to a new study, lower doses of approved immunotherapy for malignant melanoma can give better results against tumors, while reducing side effects. This is reported by researchers at Karolinska Institutet in the Journal of the National [...]
Researchers highlight five pathways through which microplastics can harm the brain
Microplastics could be fueling neurodegenerative diseases like Alzheimer's and Parkinson's, with a new study highlighting five ways microplastics can trigger inflammation and damage in the brain. More than 57 million people live with dementia, [...]
