๐๐ผ๐ ๐ฎ ๐ฆ๐ฐ๐ถ๐ฒ๐ป๐๐ถ๐ณ๐ถ๐ฐ ๐๐ฟ๐ฎ๐ป๐ฑ ๐๐ฒ๐ฒ๐ฝ๐ ๐ฎ ๐ฉ๐ฎ๐ฐ๐ฐ๐ถ๐ป๐ฒ ๐๐ป๐ฑ๐๐๐๐ฟ๐ ๐๐น๐ถ๐๐ฒ โจ Innovation shines โ even as time passes.
The global shift toward nextโgeneration mucosal vaccines has revealed a powerful truth: ๐ฎ ๐๐ฐ๐ถ๐ฒ๐ป๐๐ถ๐ณ๐ถ๐ฐ ๐ฏ๐ฟ๐ฎ๐ป๐ฑ ๐ถ๐ ๐บ๐ผ๐ฟ๐ฒ ๐๐ต๐ฎ๐ป ๐ฎ ๐ฝ๐ฟ๐ผ๐ฑ๐๐ฐ๐; ๐ถ๐ ๐ถ๐ ๐ฎ๐ป ๐ฒ๐ฐ๐ผ๐๐๐๐๐ฒ๐บ.
The recent npj Vaccines Perspective โ โCurrent status of intranasal and inhaled COVIDโ19 vaccinesโ โ highlights a remarkable fact: despite dozens of global attempts, only ๐ผ๐ป๐ฒ ๐ฎ๐ฑ๐ท๐๐๐ฎ๐ป๐๐ฒ๐ฑ ๐ฝ๐ฟ๐ผ๐๐ฒ๐ถ๐ปโ๐ฏ๐ฎ๐๐ฒ๐ฑ ๐ถ๐ป๐๐ฟ๐ฎ๐ป๐ฎ๐๐ฎ๐น ๐๐ฎ๐ฐ๐ฐ๐ถ๐ป๐ฒ reached emergency authorization and entered highโimpact literature.
This single achievement proves something essential: ๐ฎ ๐๐๐ฟ๐ผ๐ป๐ด ๐๐ฐ๐ถ๐ฒ๐ป๐๐ถ๐ณ๐ถ๐ฐ ๐ถ๐ฑ๐ฒ๐ฎ, ๐๐ต๐ฒ๐ป ๐ฏ๐ฟ๐ฎ๐ป๐ฑ๐ฒ๐ฑ ๐ฝ๐ฟ๐ผ๐ฝ๐ฒ๐ฟ๐น๐, ๐ฐ๐ฎ๐ป ๐ธ๐ฒ๐ฒ๐ฝ ๐ฎ๐ป ๐ฒ๐ป๐๐ถ๐ฟ๐ฒ ๐ถ๐ป๐ฑ๐๐๐๐ฟ๐ ๐ฎ๐น๐ถ๐๐ฒ.
Across Nature Reviews Immunology, Signal Transduction and Targeted Therapy, and The Lancet Infectious Diseases, one message is clear: ๐ฑ๐ถ๐๐ฒ๐ฟ๐๐ถ๐ณ๐ถ๐ฒ๐ฑ ๐ฝ๐น๐ฎ๐๐ณ๐ผ๐ฟ๐บ๐, ๐บ๐๐ฐ๐ผ๐๐ฎ๐น ๐ถ๐บ๐บ๐๐ป๐ถ๐๐, ๐ฎ๐ป๐ฑ ๐ถ๐ป๐ป๐ผ๐๐ฎ๐๐ถ๐๐ฒ ๐ฑ๐ฒ๐น๐ถ๐๐ฒ๐ฟ๐ ๐๐๐๐๐ฒ๐บ๐ ๐ฎ๐ฟ๐ฒ ๐๐ต๐ฒ ๐ณ๐๐๐๐ฟ๐ฒ.
This is exactly where ๐ฅ๐ฎ๐๐ถ ๐๐ผ๐ ๐ฃ๐ฎ๐ฟ๐ stands as a compelling example.
๐ Razi Cov Pars โ When Innovation Becomes Legacy
๐น ๐๐น๐ผ๐ฏ๐ฎ๐น ๐ฟ๐ฒ๐ฐ๐ผ๐ด๐ป๐ถ๐๐ถ๐ผ๐ป ๐ณ๐ฟ๐ผ๐บ ๐ฎ ๐ป๐ฎ๐๐ถ๐ผ๐ป๐ฎ๐น ๐ถ๐ป๐ป๐ผ๐๐ฎ๐๐ถ๐ผ๐ป Its presence in highโimpact literature transforms it from a domestic achievement into a scientific reference point.
๐น ๐ ๐ฝ๐ฟ๐ผ๐ฝ๐ฟ๐ถ๐ฒ๐๐ฎ๐ฟ๐ ๐ฎ๐ฑ๐ท๐๐๐ฎ๐ป๐ ๐๐ต๐ฎ๐ ๐๐ถ๐ด๐ป๐ฎ๐น๐ ๐๐ฒ๐ฐ๐ต๐ป๐ผ๐น๐ผ๐ด๐ถ๐ฐ๐ฎ๐น ๐น๐ฒ๐ฎ๐ฑ๐ฒ๐ฟ๐๐ต๐ถ๐ฝ The RASโ01 oilโinโwater adjuvant has been repeatedly cited as a novel platform โ proof that innovation can emerge anywhere.
๐น ๐ ๐ฏ๐ฟ๐ฎ๐ป๐ฑ ๐๐ต๐ฎ๐ ๐ฑ๐ผ๐ฒ๐๐ปโ๐ ๐ณ๐ฎ๐ฑ๐ฒ When a scientific brand enters peerโreviewed literature, it becomes part of the global narrative โ and science that enters the narrative never stops shining.
๐ฑ A Message to Young Scientists
๐ฆ๐ฐ๐ถ๐ฒ๐ป๐ฐ๐ฒ ๐ถ๐ ๐ฎ ๐น๐ผ๐ป๐ด ๐ด๐ฎ๐บ๐ฒ. Your work may take years to mature, but when it does, it becomes part of a legacy that outlives crises, trends, and headlines.
If one idea โ born in a national institute โ can reach global literature and influence future vaccine platforms, then your idea can too.
Keep building. Keep publishing. Keep innovating. โจ Because real science always finds its way to the light. Stรฉphane Paul Stรฉphanie Longet
As Prof Robert Clancy explains, itโs not just about fighting pathogens - itโs about understanding the ๐ฏ๐ฎ๐น๐ฎ๐ป๐ฐ๐ฒโฆ the ๐๐ถ๐ป ๐ฎ๐ป๐ฑ ๐๐ฎ๐ป๐ด of our immune system.
And when that understanding is absent? Decisions are made from an incomplete picture.
During COVID, we saw this play out - authoritative voices speaking with certaintyโฆ yet lacking foundational knowledge in this space.
Thatโs not just a gap. Thatโs a risk to public health.
This conversation isnโt about criticism - itโs about evolution.
Medicine must move forward. And that starts with asking better questions.
Whatโs your take - should immunology be rethought in modern medicine?
A very insightful review from the Akiko Iwasaki's group on the potential to harness mucosal immunity in next-generation vaccine development. While the rapid deployment of intramuscular mRNA vaccines was a landmark achievement in preventing severe COVID-19, intramuscular shots often fall short of providing sterilizing immunity. Mucosal immunity represents a particularly promising avenue for improving vaccines against respiratory viruses, as it enables immune protection to be established directly at the site of viral entry and early replication. Mucosal tissues, such as the respiratory tract, host locally regulated specialized immune cells that are functionally and spatially distinct. Reduction of infection and transmission requires engaging the mucosal immune response: a coordinated process beginning with epithelial pathogen sensing and culminating in the establishment of tissue-resident memory T (TRM) and B (BRM) cells, alongside robust local secretory IgA (SIgA) production. Unlike systemic IgG, nasal SIgA has demonstrated superior virus-neutralizing activity and greater breadth against antigenically drifted variants. A promising strategy for advancing vaccine design is the heterologous prime-boost approach. Research suggests that intramuscular priming (to establish peripheral memory pools) followed by an intranasal boost can effectively "pull" memory cells to the respiratory mucosa. However, the so-called 'mucosal' vaccines requires navigating complex physiological constraints, such as the mucociliary clearance system and the anionic mucus layer. Moreover, the regulatory path for mucosal vaccines is primarily hindered by the lack of validated correlates of protection, making it difficult to predict efficacy and guide clinical trial designs. Additionally, the anatomical proximity of the nasal mucosa to the central nervous system necessitates rigorous safety evaluations to prevent neuro-olfactory spillover or unintended neuro-inflammation. https://lnkd.in/eb5ZUMY4
Beginning with Edward Jennerโs discovery of the smallpox vaccine, the ever-expanding repertoire of vaccines against pathogens has saved many lives. During the COVID-19 pandemic, a revolutionary mRNA injectable vaccine emerged that effectively controlled the severity of disease caused by SARS-CoV-2. This vaccine induced potent antigen-specific neutralizing serum IgG antibodies, but was limited in its ability to prevent viral invasion at the respiratory surfaces. Nasal vaccines have attracted attention as a potential strategy to combat respiratory infections and prepare for future pandemics. Input from disciplines such as microbiology, biomaterials, bioengineering and chemistry have complemented the immunology to create innovative delivery systems. This approach to vaccine delivery has yielded nasal vaccines that induce secretory IgA as well as serum IgG antibodies, which are expected to prevent pathogen invasion, thereby diminishing transmission and disease severity. For a nasal vaccine to be successful, the complexity of the relevant anatomical, physiological and immunological properties, including the proximity of the central nervous system to the nasal cavity, must be considered. In this Review, we discuss past and current efforts as well as future directions for developing safe and effective nasal vaccines for the prevention of respiratory infections. This Review provides an overview of progress and future directions in the development of nasally administered vaccines for respiratory infections.
The olfactory mucosa is a component of the nasal airway that mediates the sense of smell. Recent studies point to an important role for the olfactory mucosa as a barrier to both respiratory pathogens and to neuroinvasive pathogens that hijack the olfactory nerve and invade the CNS. In particular, the COVID-19 pandemic has demonstrated that the olfactory mucosa is an integral part of a heterogeneous nasal mucosal barrier critical to upper airway immunity. However, our insufficient knowledge of olfactory mucosal immunity hinders attempts to protect this tissue from infection and other diseases. This Review summarizes the state of olfactory immunology by highlighting the unique immunologically relevant anatomy of the olfactory mucosa, describing what is known of olfactory immune cells, and considering the impact of common infectious diseases and inflammatory disorders at this site. We will offer our perspective on the future of the field and the many unresolved questions pertaining to olfactory immunity. This Review from Wellford and Moseman considers the unique immunology of the olfactory mucosa. The authors describe how stromal cells, innate immune cells and adaptive immune cells cooperate to defend the olfactory mucosa, protecting the host from potentially serious respiratory or neurotropic infections. They also discuss the relevance of olfactory mucosal immunology for the fields of vaccination and neurodegeneration.
Abstract. Established evidence indicates that oral microbiota plays a crucial role in modulating host immune responses to viral infection. Following severe
Researchers have developed a novel intranasal COVID-19 vaccine that enhances the immune systemโs response to the virus, providing longer-lasting, greater protection than vaccine injections, even against new and emerging variants.
Abstract The mucosal system, which includes the respiratory, gastrointestinal, and urogenital tracts, serves as a primary entry point for pathogens, with a unique immune microenvironment and specialized defense mechanisms. In recent years, especially following the onset of the COVID-19 pandemic, there has been increasing recognition of the importance of mucosal immunity, motivated by an enhanced comprehension of its fundamental mechanisms. Currently, strategies based on mucosal delivery systems to administer antigens and induce strong mucosal protective immunity have become a key focus in the development of mucosal vaccines. Compared with conventional intramuscular delivery, mucosal vaccination can simultaneously elicit a robust local mucosal response, effectively block pathogen entry into the local mucosa, and generate systemic immune responses to prevent symptomatic infections and severe disease. In addition, mucosal delivery offers advantages such as ease of administration and low invasiveness, making it a more widely acceptable approach to vaccination. In the present study, we conducted a systematic review of the mechanisms of mucosal immunity, the technological platforms for mucosal vaccines, and proposed a perspective on the challenges and future directions for the development of next-generation mucosal vaccines, with the goal of enhancing public knowledge and awareness regarding mucosal immunity and its possible effects on global health.
Pre-eclampsia is often described as a disease of the placenta, but at its core it is also a disease of immune balance. When the maternal immune system becomes overactivated, the delicate vascular architecture of the placenta can begin to fail.
Recent data showing rising pre-eclampsia rates after the pandemic has prompted renewed interest in immune-vascular triggers. If spike protein interacts with macrophages and endothelial cells in the placenta, understanding that mechanism could become a crucial piece of the puzzle in protecting maternal and fetal health.
======================================================== Your Gut Readiness Assessment https://lnkd.in/ezPm4wht ========================================================
Nasal spray vaccine could โreplace multiple jabs every yearโBookmark popoverRemoved from bookmarksClose popoverScientists at Stanford Medicine have developed a universal vaccine formula, tested on mice, that offers broad protection against various respiratory threats. The vaccine, delivered as a nasal spray, could protect against cold, flu, Covid, allergies, respiratory viruses, sepsis-causing bacteria, and even house dust mites. It works by mimicking the signals immune cells use to communicate during an infection, rather than targeting specific parts of a pathogen. If developed for humans, this vaccine could replace multiple annual jabs for winter respiratory infections and potentially protect against new pandemic bugs. While lead author Dr Bali Pulendran estimates human availability within five to seven years, other experts caution that a truly universal vaccine is still some way off due to safety considerations and the diversity of the human population.
A Review of Currently Licensed Mucosal COVID-19 Vaccines -
Recent review on mucosal COVID-19 vaccines approved by the FDA. Unlike most injectable vaccines, they induce a robust mucosal immune response with secretory IgA antibodies. Mucosal vaccines also lead to a strong systemic cellular and humoral immune response.
To date, only five active mucosal vaccines have received regulatory approval for human use, and at least 29 are under clinical trials. Approved vaccines use intranasal, sometimes also combined with intramuscular doses. Most of them utilize replication incompetent viruses (e.g. adenovirus) to deliver the antigen to the nasal mucose via nasal sprays or nebulizers.
๐ Le futur des vaccins : des solutions nasales contre les infections respiratoires ๐ฆ ย Dans le cadre de la Semaine Europรฉenne de la Vaccination, dรฉcouvrez les derniรจres innovations dans le domaine des vaccins, avec un focus particulier sur les vaccins nasaux permettant une protection plus efficace et ciblรฉe. ๐ ย ๐ Ces solutions novatrices sont dรฉveloppรฉes pour protรฉger les gรฉnรฉrations futures contre des infections respiratoires graves telles que la coqueluche, la pneumonie ร pneumocoques, et les virus comme la #grippe et le Covid-19. ๐ซ ย Des chercheurs europรฉens, dont lโInstitut Pasteur de Lille, sont ร la pointe de ces dรฉcouvertes avec des projets comme :ย ๐ข BPZE1 : Un vaccin nasal contre la coqueluche en dรฉveloppement, il bloque la transmission et offre une protection durable, avec des rรฉsultats positifs chez les enfants et adultes ! ๐ ๐ข Vaccin nasal contre les pneumocoques : Ce vaccin protรจge contre toutes les souches de pneumocoques, une avancรฉe importante pour protรฉger les plus vulnรฉrables ! ๐ถ๐ต ย ย ๐ Pour en savoir plus, rendez-vous sur pasteur-lille.frย
The โFerrari of virusesโ is having a banner season. Norovirus, which races through cruise ships, homes, and long-term care facilities, is experiencing a remarkable winter surge in the Northern Hemisphere, sending large numbers of people racing to the bathroom and many others to the hospital, and in rare cases, proving fatal. In the United States, for example, 91 outbreaks of the intestinal virus occurred in the first week of December 2024, far above the previous maximum, 65, for the same week between 2010 and 2024. And levels of its genes in U.S. wastewater are an order of magnitude above last year. โThe early data for the early part of the season is certainly supporting that weโre going to have a pretty intense norovirus year,โ says Lisa Lindesmith, who studies the virus at the University of North Carolina (UNC) at Chapel Hill. Some of the surge may be due to a new variant of the virus, unfamiliar to many peopleโs immune systems, and the resumption of cruises and other gatherings that the COVID-19 pandemic interrupted. And thereโs no vaccine anywhere in sight: The most advanced candidate just failed a key trial and others wonโt be ready for several years. Norovirus thrives in cold climes, causing explosive diarrhea and vomiting that typically only last for a day. But several weeks after people recover, they can still shed the virus, and it can remain infectious for long periods on surfaces. Itโs notoriously resistant to many disinfectants, and studies in adult volunteers have shown just a trace of virus is enough to sicken a person. Oysters are also a source of infection, because the filter-feeding mollusks concentrate the virus from contaminated water in their tissues. U.S. health officials issued several warnings about infected oysters in December, and France has banned oyster harvesting in certain regions because of norovirus outbreaks.
ย
For most people the virus is a rapidly passing misery that creates the wrong kind of unforgettable memories from a wedding or a holiday gathering. But, โIt can be pretty severe,โ says Mary Estes, a virologist at the Baylor College of Medicine who is a leading researcher in this small field. Although norovirus-related mortality is low in wealthy countries, it kills an estimated 200,000 young children in the developing world each year. Even in the U.S., itโs the leading cause of hospitalization for diarrheal disease, hitting young children and the elderly particularly hard. Immunocompromised people, particularly cancer patients on chemotherapy or transplant recipients taking antirejection drugs, can have chronic infections that last for months or even years. Many sickened people also miss work, globally leading to an estimated $60 billion in annual losses. Given that symptoms quickly resolve in most cases, few people seek care, but in the U.S., reports of norovirus-related outbreaksโtwo or more illnesses from a common sourceโthis winter promise to far outstrip the 2500 typically seen. Cruise ships are being hit hard, too. In the United Kingdom, labs that test for the virus reported 63% more positive samples in the last 2 weeks of 2024 than the average, and hospitalizations were up 11%.
ย
Albert Kapikian at the U.S. National Institutes of Health discovered the first norovirus in 1972 from an outbreak of โwinter vomiting diseaseโ that occurred at an elementary school in Norwalk, Ohioโhence the โnoroโ in the name. Scientists have since described more than 30 major variants that circulate in humans, distinguished by changes in their surface protein, VP1, which is the main target of antibodies that can โneutralizeโ it. โThis virus is really good at getting around antibodies,โ says veteran norovirus researcher Christine Moe of Emory University. โI used to think it was the most successful pathogen until COVID came along.โ The world had four massive waves of norovirus between 2002 and 2012โโthe most pandemics of any virus in the 21st century,โ says UNCโs Ralph Baric, who has long studied the pathogen. Each erupted when a new norovirus variant replaced the dominant one. But since 2012, a set of related variants called GII.4 has held sway. โOne of the hottest topics in norovirus research is why, after having those really frequent replacement events, has that process slowed down?โ says Lindesmith, who works in Baricโs lab. A change that could help explain this winterโs surge in cases is the success of GII.17, a variant that has circulated at low levels for decades. GII.17 began to rise in the U.S. and six European countries last year, a 26 September 2024 paper in Eurosurveillance reported. According to the U.S. Centers for Disease Control and Prevention, 70% of 56 viral isolates sequenced between 1 September and the end of the year belong to the GII.17 lineage. The U.K. and the Netherlands are also seeing GII.17 dominate. Whether it will end GII.4โs 12-year reign as the dominant variant wonโt be clear for many months.
ย
What finally gave GII.17 an edge isnโt clear. Norovirus research Miranda de Graaf at the Erasmus Medical Center says the virus found in the Netherlands has significantly mutated away from other GII.17 strains. The drop in norovirus transmission because of social distancing during the COVID-19 pandemic may also have played a role. โIf you go 3 or 4 years without much exposure in the population, the prediction would be that that background immunity is going to drop over time, and then thereโs going to be a big surge that occurs sometime after as things return to normal,โ Baric says. A norovirus vaccine likely would have a large global market among all ages, but development was slow off the mark. โIt took a long time for people to recognize that these viruses really are infecting a lot of people,โ Estes says, which limited funding for the research. The virus is also a challenge to work with; it can only grow reliably in a complicated organoid culture system, developed by Estes and co-workers, that mimics human intestines. The most advanced vaccine candidate, which contained โviruslike particlesโ made of VP1, failed in an efficacy trial in infants, its manufacture, HilleVax, reported in July 2024. A Chinese company, Zhifei, has an efficacy trial underway in children of a candidate that contains VP1s from four genotypes, including GII.4 and GII.17. And Moderna in September 2024 launched an efficacy trial in adults of a vaccine that uses messenger RNAs encoding VP1s from multiple variants (although not GII.17). Even if a norovirus vaccine proves safe and effective, it is up against what Baric calls โone of the most infectious viruses in nature,โ which means a vaccine is unlikely to prevent all symptoms and completely stop transmission. It would probably also require regular boosters. โThis is not going to be a one-and-done sort of vaccination,โ Lindesmith says. But like COVID-19 vaccines, a norovirus vaccine might slow spread and spare people from severe disease or even deathโkeeping one day of misery from turning into something much worse.
The findings, published July 31 in Science Advances, provide further evidence that so-called mucosal vaccines sprayed into the nose or dropped into the mouthโฆ
Currently, SARS-CoV-2 has evolved into various variants, including the numerous highly mutated Omicron sub-lineages, significantly increasing immune evasion ability. The development raises concerns about the possibly diminished effectiveness of available vaccines and antibody-based therapeutics.
The development of effective SARS-CoV-2 vaccines has been essential to control COVID-19, but significant challenges remain. One problem is intramuscular administration, which does not induce robust mucosal immune responses in the upper airwaysโthe primary site of infection and virus shedding. Here we compare the efficacy of a mucosal, replication-competent yet fully attenuated virus vaccine, sCPD9-ฮFCS, and the monovalent mRNA vaccine BNT162b2 in preventing transmission of SARS-CoV-2 variants B.1 and Omicron BA.5 in two scenarios. Firstly, we assessed the protective efficacy of the vaccines by exposing vaccinated male Syrian hamsters to infected counterparts. Secondly, we evaluated transmission of the challenge virus from vaccinated and subsequently challenged male hamsters to naรฏve contacts. Our findings demonstrate that the live-attenuated vaccine (LAV) sCPD9-ฮFCS significantly outperformed the mRNA vaccine in preventing virus transmission in both scenarios. Our results provide evidence for the advantages of locally administered LAVs over intramuscularly administered mRNA vaccines in preventing infection and reducing virus transmission. In this study, the authors evaluated the protective capacity of a mucosal, live-attenuated SARS-CoV-2 vaccine and show that it induces systemic and mucosal humoral immunity, protects from clinical disease symptoms, and prevents virus transmission in hamsters more efficiently than an intramuscular mRNA vaccine.
Researchers at Karolinska Institutet have shown that nasal drops with IgA antibodies can protect mice from SARS-CoV-2 infection. The results imply a new way to protect individuals at high risk from different variants of the SARS-CoV-2 virus and possibly other infections. The study is published in PNAS.
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