Amplification of IN with a stabilized spike of SARS-CoV-2 induces mucosal humoral memory. (A) Experimental design: Mice were immunized intramuscularly (IM) with 1 μg of mRNA-lipid nanoparticles (LNPs) encoding the adhesion protein of full-length SARS-CoV-2 (SCV2) (Pfizer/BioNTech BNT162b2), followed by intranasally (IN). ) immunization with 1 μg of fusion-stabilized (Hexapro), trimeric recombinant SCV2 protein 14 days after mRNA-LNP immunization. Fourteen days after the acute injection, serum, bronchoalveolar lavage (BALF), and nasal lavage fluids were collected to assess antibody binding and neutralization responses. Lung tissues were collected for extravascular B-cell analysis. (B to G) Measurement of SCV2 spike S1 subunit-specific nasal IgA (B), nasal lavage IgG (C), BALF IgA (D), BALF IgG (E), serum IgA (F), and serum IgG (G) in naive mice, mice immunized with mRNA-LNP IM (IM Prime), mice immunized with IN spike protein (IN Spike), or IM primed and IN spike-boosted (P&S) mice. (H to K) Measurement of the neutralization titer against SCV2 pseudotyped vesicular stomatitis virus (VSV) in CSF (H) and serum (I). (J to N) Using intravenous (IV) CD45 labeling, different extravascular (antibody negative for IV labeling) B cell subsets were measured, including RBD tetramer-binding B cells, resident IgA+ memory (BRM) B cells , IgG+ BRM cells, IgA+ antibody-secreting cells (ASCs), and IgG+ ASCs in lung tissues from IM Prime or P&S mice. Mean ± sem Statistical significance was calculated by [(B) to (G)] one-way ANOVA or [(H) to (N)] Student’s Test; *P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001, ****P ≤ 0.0001. Individual data points are represented and pooled from two or three independent experiments. credit: Science (2022). DOI: 10.1126/science.abo2523
A nasal vaccine developed by Yale University may help boost the immune response to COVID-19 in previously vaccinated animals and reduce transmission of the virus, Yale researchers report Oct. 27 in the journal Science.
New vaccine an approach developed by Yale researchers known as “prime and thorn“— designed for a quick start immune response in respiratory systemwhich is the first part of the body to be infected by the virus.
The intramuscular shots of the vaccine that most people have received to protect against the COVID-19 infection provide a broad immune response throughout the body and help prevent serious illness. However, this protection tends to wane after about four months, leaving people susceptible to breakthrough infections and new variants.
A new “prime” and “spike” approach could help prevent breakthrough infections in vaccinated people by boosting the immune response inside the lining of the airways, which are the first cells that are attacked by COVID-19. (“Prime” refers to the process of injecting the vaccine directly into the muscle, as is commonly done. “Spiked” refers to the subsequent vaccination with adhesion proteins known to come from the coronavirus, directly into the nostril, where the virus is known to enter the body. )
“The nasal vaccine promotes the development of immunity in the respiratory system, which can respond more quickly to infection,” said Dr. Benjamin Goldman-Israelov, associate professor of medicine (infectious diseases) at Yale School of Medicine and co-author of the article. “By creating mucosal immunity, the vaccine helps stop the virus at the point of entry, rather than waiting to fight back.”
The Yale team, led by Goldman-Israel and Tianyang Mao, a graduate student in the lab of fellow co-author Akiko Iwasaki, Sterling Professor of Immunobiology, delivered the nasal vaccine to both vaccinated and unvaccinated mice. They found an increased immune system response only in the airways of vaccinated mice. Naïve mice and vaccinated mice that did not receive the nasal vaccine died from infection. Meanwhile, mice that received an intranasal booster were completely protected from death and disease.
U hamsters who received the nasal vaccine, the Yale team found a reduced duration and total amount of virus that occurs when an infected individual releases copies virus including through sneezing or coughing. Hamsters vaccinated with the prime and spike method also showed reduced viral loads when housed in the same cage as infected unvaccinated hamsters, suggesting that the strategy reduces transmission routes.
The researchers also found an increased breadth of immune response among animals that received the nasal vaccine, indicating that the approach would be effective against a wide range of coronaviruses with pandemic potential.
Goldman-Israelov noted that the Yale approach does not use live viruses, viral vectors or adjuvants, which could make the vaccine safer.
Tianyang Mao et al. Intranasal vaccine without adjuvants induces protective mucosal immunity against sarbecaviruses, Science (2022). DOI: 10.1126/science.abo2523
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