It started with a tickle in your throat. Then, it evolved into congestion, and maybe a little cough. Perhaps you lost your voice.
You might have had a slight fever that went away with ibuprofen, but you never felt bad enough to stay in bed all day.
So, which respiratory virus was invading your cells?
There are several types of viruses that could be the culprit: respiratory syncytial virus (RSV), influenza, parainfluenza viruses, metapneumovirus, rhinoviruses, coronaviruses, enteroviruses, and adenoviruses are among the most common.
However, most people who are infected will probably never know which one rallied their immune system.
"They are hard to distinguish one from the next because they all have similar respiratory symptoms of congestion, cough, runny nose, fever. They all start that way," said Paul Offit, MD, of Children's Hospital of Philadelphia. "There's really no distinguishing them unless you test."
Testing isn't likely to happen unless you're hospitalized. A typical Quest Diagnostics respiratory panel, for example, includes adenovirus, influenza, parainfluenza, rhinovirus, enterovirus, metapneumovirus, and RSV.
"Typically what we see at Children's Hospital of Philadelphia in winter is RSV, number one; and right behind it is influenza," Offit said. "Then, you'll see things like human metapneumovirus, parainfluenza virus, adenovirus."
This year, he said, there seems to be more of a "bi-demic" rather than a "tri-demic" of winter respiratory illness, with RSV and influenza causing the most problems for hospitals. Luckily, SARS-CoV-2 hasn't caused a huge burden of illness this year, Offit said.
Outside of hospitalization, respiratory virus testing isn't as common because there are no at-home tests for any of those viruses except for SARS-CoV-2.
Without widespread testing, there's less surveillance data on infections, so it's hard to know just how much morbidity happens in any given year from any given virus.
"We do not track morbidity or mortality of all of these viruses," said William Schaffner, MD, professor of infectious diseases at Vanderbilt University Medical Center in Nashville, Tennessee. "We know in general that many of them are seasonal, increasing in late fall, winter, and into spring, and they provide the great background of viral infections with which every human on this planet is familiar -- the runny nose, the sore throat, feeling out of sorts for a day or 2 or 3 and then slowly getting better."
While all of these viruses typically prompt similar symptoms, there are a few known to have particular manifestations, such as parainfluenza being responsible for the majority of croup in children, and RSV being a frequent cause of bronchiolitis in infants.
Here are the key features and differences among each of the most common annual respiratory nuisances.
Respiratory Syncytial Virus
RSV is a single-stranded RNA virus in the Pneumoviridae family and the Orthopneumovirus genus. It was first isolated in 1955 from chimpanzees with respiratory illness at the Walter Reed Army Institute of Research, according to a report in Nature.
It's the most common cause of bronchiolitis in infants, and can be severe in older adults as well. Up to 10,000 adults die each year in the U.S. from RSV, Offit noted.
"RSV has this reputation as a pediatric virus, but over the last 15 years, we've accumulated data that people over 65, particularly those with underlying lung or heart disease, can be affected by RSV just as severely as influenza," Schaffner said. "And in some years the impact of RSV has been as serious as the impact of flu."
In most cases, however, symptoms are usually mild and resemble the common cold. These include congestion, runny nose, sneezing, dry cough, low-grade fever, and sore throat.
Influenza is an RNA virus in the Orthomyxoviridae family and its most common subtypes are A and B. Infection typically leads to more severe symptoms than the common cold. These include fever, aches, fatigue, cough, and sore throat.
People infected with influenza are most contagious in the 3 to 4 days after the illness starts, according to the CDC.
The virus can be more severe in young children and in older adults, and the U.S. typically sees some 20,000 to 25,000 influenza deaths per year, though that number can reach as high as 60,000 annually, Offit said.
These single-stranded RNA viruses belong to the Paramyxoviridae family, and fall into two genera: Respirovirus and Rubulavirus, and overall there are four types (1-4) and two subtypes (4a and 4b), according to the CDC.
Parainfluenza viruses are the most common culprit in cases of croup, infamous for terrifying parents with the raspy sound of stridor.
By age 5, almost all children are seropositive, and people can be reinfected multiple times in their lifetime, resulting in mild illness with cold-like symptoms. Older adults and people who are immunocompromised have a higher risk of severe infection, according to the CDC.
This single-stranded RNA virus in the Paramyxoviridae family was discovered in the Netherlands in 2001, but evidence suggests its been in circulation for at least 5 decades, according to the Encyclopedia of Microbiology.
Common symptoms include cough, fever, and congestion, but it can lead to more severe disease in young children, older adults, and people who are immunocompromised, according to the CDC.
Rhinoviruses are the most common cause of the common cold, according to the CDC. These single-stranded RNA viruses belong to the Picornaviridae family and have three types: A, B, and C.
They were first isolated in the 1950s by Winston Price, MD, at Johns Hopkins University in Baltimore, during an effort to identify the cause of the common cold.
While coronaviruses are now widely known due to the pandemic of SARS-CoV-2, four subtypes previously had been responsible for respiratory disease in the U.S. Those include 229E, OC43, NL63, and HKU1, which have typically been associated with mild cold-like symptoms.
Two other coronaviruses, the original SARS-CoV and MERS-CoV, have caused more severe disease in humans.
These single-stranded RNA viruses are known for their distinct surface spikes, which supply them a crown-like appearance.
Most people infected with an enterovirus have asymptomatic infections or only mild, cold-like illness. Of the more than 100 non-polio enteroviruses, the most common ones are EV-D68, EV-A71, and coxsackie virus A6 (CV-A6), according to the CDC.
EV-D68 more commonly causes respiratory illness, while EV-A71 and CV-A6 can cause hand, foot, and mouth disease. While EV-D68 is usually asymptomatic or causes only mild symptoms, it can in rare cases cause acute flaccid myelitis (AFM).
These DNA viruses in the family Adenoviridae are frequently accompanied by small, single-stranded DNA parvoviruses known as adeno-associated viruses, that don't seem to cause any specific disease. In fact, most experimental gene therapies have switched from using adenoviruses to these adeno-associated viruses to mitigate some of the side effects.
Most adenovirus infections are asymptomatic, and when they do cause symptoms, these are mostly mild. They can also range widely in the type of disease they cause.
"Adenoviruses are interesting. Some are directed more at the respiratory tract, while some have more intestinal symptoms and others like to supply us pink eye," Schaffner said. "That viral family is very diverse and often the major impact is quite strain-specific."
Medical Respiratory and Ventilation Motors
This design uses a ventilator electric motor to power a BVM-bridge ventilator, automating what is usually a manual process.
NEW YORK, NY, UNITED STATES, November 25, 2022 /einpresswire.com / -- Market.Biz published research on the Global medical respiratory and ventilation motors market covering the micro-level of analysis by competitors and key business segments (2022-2030). The Medical Respiratory and Ventilation Motors market explores a comprehensive study of various segments like opportunities, industry size, share Product Type [DC; AC], and Application [Hospital; Clinic] development, innovation, sales, and overall growth of major key players [FAULHABER Group; Portescap; Allied Motion; Infineon Technologies; Maxon; Dentsply Sirona; Danaher; Morita; A-Dec Inc.; W&H-Group; COXO; Denjoy; Aseptico Inc.]. Sector research is conducted on primary and secondary statistical sources and consists of qualitative and quantitative details.
Various factors are responsible for the market's growth, which are studied at length in the report. In addition, the report lists the restraints that are posing threat to the Medical Respiratory and Ventilation Motors market. This report is a consolidation of primary and secondary research, which provides business size, share, dynamics, and forecasts for various segments and sub-segments considering the macro and micro environmental factors.
This design uses a ventilator electric motor to power a BVM-bridge ventilator, automating what is usually a manual process. The power source for the ventilator motor controls is either a notebook battery brick or a backup system using an MPSDC/DC boost board.
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The Medical Respiratory and Ventilation Motors market research report delivers a comprehensive analysis of industry size, trends, and business growth prospects. This report also provides detailed information on technology spending for the forecasting period, which gives a unique view of the Medical Respiratory and Ventilation Motors market across numerous segments.
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The main objective of the report is to provide companies in the sector with a strategic analysis of the impact of covid-19. The sudden emergence of the covid19 epidemic led to the introduction of severe form lockdown laws in some countries, causing delays in importing and exporting Medical Respiratory and Ventilation Motors markets. The application and the leading countries study and assess the potential of the Medical Respiratory and Ventilation Motors industry including statistical data on business dynamics, growth factors, key challenges, growth analysis, and analysis of business entry strategy, opportunities, and forecasts.
The Medical Respiratory and Ventilation Motors industry is segmented in this report based on manufacturers, regions, product types, and applications. The study can help understand the industry and define progress strategies for the company / key players. Provides a detailed analysis of new entrants or existing competitors in the keyword industry, ranging from industry positioning and marketing channels to potential growth strategies.
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Region of the Medical Respiratory and Ventilation Motors market:
➛ North America (the United States, and Canada, Mexico)
➛ Europe (UK, Germany, France, Italy, and Russia)
➛ Asia-Pacific (Japan, Korea, India, China, and Southeast Asia)
➛ South America (Argentina, Colombia, and Brazil)
➛ The Middle East and Africa (Saudi Arabia, Nigeria, Egypt, UAE, and South Africa)
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NEW YORK — The U.S. flu season keeps getting worse.
Health officials said Friday that 7.5% of outpatient medical visits last week were due to flu-like illnesses. That's as high as the peak of the 2017-18 flu season and higher than any season since.
The annual winter flu season usually doesn’t get going until December or January, but this one began early and has been complicated by the simultaneous spread of other viruses.
The measure of traffic in doctor's offices is based on reports of symptoms like coughs and sore throats, not on lab-confirmed diagnoses. So it may include other respiratory illnesses.
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That makes it hard to compare to flu seasons from before the COVID-19 pandemic. Other years also didn't have this year's unusually strong wave of RSV, or respiratory syncytial virus, a common cause of cold-like symptoms that can be serious for infants and the elderly.
Meanwhile, 44 states reported high or very high flu activity last week, the Centers for Disease Control and Prevention said Friday.
That may not bode well for the near future. It's likely there was more spread of respiratory viruses during Thanksgiving gatherings and at crowded airports, experts say.
The dominant flu strain so far is the kind typically associated with higher rates of hospitalizations and deaths, particularly in people 65 and older.
The CDC estimates there have been at least 78,000 hospitalizations and 4,500 deaths from flu so far this season. The deaths include at least 14 children.
Flu shots are recommended for nearly all Americans who are at least 6 months old or older.
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are currently stressing hospitals across California.
Children's Health of Orange County Hospital (CHOC) in Orange is setting up patient beds in every possible space available, even in the lobby.
The Orange County Board of Supervisors voted Tuesday to extend an emergency declaration to help CHOC cope with the ongoing surge of patients with upper respiratory viruses.
The emergency declaration helps CHOC obtain Tamiflu, albuterol and other medications that have been in short supply across the U.S.
The hospital has set up patient beds in spaces including the discharge lounge, in an oncology playroom gym and in surgical playrooms. The emergency lobby has been extended into the hospital's driveway.
CHOC officials said the hospital is seeing more than 150 children per day in the lobby, and has been averaging 410 emergency-room visits, with as many as 489 one day. That's more than double the usual amount of ER visits, officials said.
RSV (respiratory syncytial virus) and flu cases are up 25 percent in an "already record-breaking year," according to CHOC Chief Medical Officer Dr. Sandip Godambe.
January and February are usually the peak months for the viruses, so it's unclear if this wave will just continue or worsen through the winter, Godambe said.
More and more people are bringing back masks as we get deeper into the holiday season. Medical experts say there are definitely more people getting sick in accurate weeks and they say people are trying to better protect themselves using what worked during the pandemic.
In Jamaica Plain – masks are still required by some businesses to get in the door. “We don’t want workers to get sick. We care about them too and we rely on them,” a customer said. Coming off Thanksgiving and more people getting sick in general – masks seem to be on a comeback. “A lot of people I try to wear a mask. I don’t like it, I don’t enjoy it but I don’t want to get sick,” said the customer.
Doctor Shira Doron is the Hospital Epidemiologist at Tufts Medical Center. She says there is an uptick in covid and all respiratory viruses. “Sounds like some parts of NY have reached their orange level. In that orange level the CDC recommends wearing masks indoors,” said Doron.
Back when the mask mandate was lifted last year people thought there would be no looking back. Dr Doron says masks have now become an important tool for staying healthy. “What we have learned from the pandemic is people can choose to protect themselves with a high quality, well-fitting mask,” said Doron. “It actually works better when people assess their own risk and take it upon themselves to protect themselves”
The Dr also explained that even though Boston is seeing higher covid numbers in the wastewater – hospitalizations are still on a safe zone so there is no CDC mask recommendation locally.
This is a developing story. Check back for updates as more information becomes available.
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SANTA FE, N.M. (KRQE) – The New Mexico Department of Health (NMDOH) issued a public health emergency order on Thursday. Officials said there is a notable strain on the healthcare system at this time.
NMDOH declared an emergency order due to the spike in pediatric cases and hospitalizations of respiratory viruses.
One of these viruses is the respiratory syncytial virus (RSV), which is known to affect small children and babies. RSV is spread through droplets produced by coughing and sneezing.
“We expand our social networks during the holidays, which is an important part of nurturing ourselves as human beings living in a complex world. However, at the same time we create more opportunities for respiratory viruses to spread,” said Acting Department of Health Secretary David Scrase, “It’s important to take steps to reduce the risk for respiratory viruses by practicing the good health and hygiene habits we’ve learned over the past few years as New Mexico nurses, doctors and hospital staff are facing another surge.”
The order was issued because hospitals and emergency rooms are being strained as they are seeing a surge in respiratory viruses.
“In light of the increasing numbers of children being hospitalized with RSV, and the number of children presenting to the Emergency Departments statewide, it is really important at this time to take these precautions recommended by the New Mexico Department of Health, especially not exposing our children to others that are currently experiencing respiratory symptoms,” said CHRISTUS St. Vincent Chief Medical Officer David Gonzales.
New Mexico saw RSV cases begin to increase in October and November alongside other respiratory illnesses like COVID-19 and influenza.
The state recommends the following steps to slow the spread of illnesses.
Nearly 20,000 people in the United States were admitted to the hospital for flu last week, almost double the number of admissions from the week before, according to data updated Friday by the US Centers for Disease Control and Prevention.
The CDC estimates that there have been at least 8.7 million illnesses, 78,000 hospitalizations and 4,500 deaths from influenza this season.
In a letter to the nation’s governors Friday, US Health and Human Services Secretary Xavier Becerra notes that flu and other respiratory viruses are “increasing strain” on the country’s health care systems.
In a letter obtained exclusively by CNN, Becerra wrote that the Biden administration “stands ready to continue assisting you with resources, supplies, and personnel.”
Last month, children’s health leaders requested a formal emergency declaration from the federal government to support hospitals and communities amid an “alarming surge of pediatric respiratory illnesses, including respiratory syncytial virus (RSV) and influenza, along with the continuing children’s mental health emergency.”
The Biden administration has not declared a public emergency for RSV or flu, but the Becerra letter outlines ways the public health emergency declaration for Covid-19 can be applied to more broadly address challenges brought on by a confluence of Covid-19 and other respiratory and seasonal illnesses.
“The Administration has exercised regulatory flexibilities to help health care providers and suppliers continue to respond to COVID-19. These flexibilities – while critical in addressing the COVID-19 pandemic – can also help address many of the challenges you face during the spread of non-COVID-19 illnesses, including RSV and flu,” the letter says. “They remain available to you and health care providers as you all make care available in response to flu, RSV, COVID-19, and other illnesses.”
For example, if a hospital has staffing shortages that have been exacerbated by the Covid-19 pandemic, it may use a waiver that would allow increased surge capacity or easier patient transfers – even if the patients need treatment for something other than Covid-19, such as flu or RSV.
The letter also highlights available funding, including $400 million from the US Centers for Disease Control and Prevention to prepare for and respond to public health threats each year, including flu and other respiratory diseases such as RSV, along with data, analysis and other planning resources put together by the federal government. It also notes that the federal government is monitoring the supply chain for critical drugs and devices and that federal health officials over the past month have been engaging with the nation’s governors through a meeting hosted by the National Governors Association.
“As your federal partner, we stand ready to evaluate any request for federal medical assistance and support – including requests for medical personnel and equipment – working in close coordination with you and local jurisdictions to determine the needs and availability of matching resources,” Becerra wrote.
Flu activity has been highest in the South, with hot spots spreading from El Paso to southwest Virginia. All but six states are experiencing “high” or “very high” respiratory virus levels, and seasonal flu activity remains “high and continues to increase,” according to the CDC.
There have been nearly 17 flu hospitalizations for every 100,000 people this season, rates typically seen in December or January. The cumulative hospitalization rate hasn’t been this high at this point in the season in more than a decade.
The latest surveillance data probably does not reflect the full effects of holiday gatherings, as it only captures through November 26, two days past Thanksgiving.
While flu continues to ramp up, RSV has shown signs of slowing nationwide, but test positivity rates are still higher than they’ve been in years, and cumulative hospitalization rates are about 10 times higher than typical for this point in the season. Less than two months in, the RSV hospitalization rate this season is already nearing the total RSV hospitalization rate from the entire 2018-19 season.
There is no vaccine for RSV, but health officials have urged people to get their flu shots and updated Covid-19 boosters heading into winter. With the holiday season – and flu season – underway, Dr. Anthony Fauci warned this week of the potential for an emergency situation.
“When you have very little wiggle room of intensive care beds, when you have like almost all the intensive care beds that are occupied, it’s bad for the children who have RSV and need intensive care. But it also occupies all the beds, and children who have a number of other diseases that require intensive care or ICU, they don’t have the bed for it,” Fauci, director of the National Institute of Allergy and Infectious Diseases, said on CBS’s “Face the Nation” on Sunday. “So if you get to that situation, that’s approaching an emergency.”
The holiday season is here, but so is a season of sickness. Respiratory illnesses have people heading to hospitals to get medical care, overloading the system.
VANCOUVER, Wash. — Everyone is looking for a break after long years living with COVID-19, but the coronavirus is not done with us yet — and health officials warn that it's accompanied by a strong onset of RSV, or respiratory syncytial virus, and what is developing into a severe flu season.
There are a variety of viruses circulating out there, with RSV affecting young children the worst. All this has hospitals in both Washington and Oregon beyond stressed.
In fact, local pediatric hospitals are working in crisis mode to accommodate all the young patients. And emergency rooms at all hospitals are packed.
“In Clark County we're seeing a significant increase in respiratory illness, and it's gotten to the point where it's having an impact on our local urgent cares and hospitals,” said Dr. Alan Melnick, Clark County Public Health director.
The impact at PeaceHealth Southwest Washington Medical Center is real — a hospital that normally would average between 280 and 310 patients right now is virtually full, caring for up to 380 patients, and an emergency department with 42 beds is holding 120 to 130 patients.
“We're seeing people wherever we can, we're opening up new units, we're getting a lot of support from the hospital in terms of being able to see patients in other areas. But at a certain point there are just a lot of people needing care at once,” said Dr. Jason Hanley.
The medical director of the PeaceHealth Southwest Emergency Department commends his staff for stepping up to meet the need. But public health officials say there are ways that we can help.
Clark County Public Health wants people to be aware and take precautions, to avoid getting sick if possible. That starts with vaccinations. Melnick strongly encourages everyone eligible to be up-to-date on both COVID-19 and influenza vaccines and boosters.
“I don't think there's anything abnormal about going in and getting a vaccine," Melnick said. "It's pretty quick, it's pretty easy and it's incredibly safe.”
Melnick said that if you or your child do get a respiratory illness with mild symptoms, start by treating them at home. If there is no improvement or worsening of symptoms, call your primary care provider first, or go to an urgent care clinic if needed.
“Certainly if you or your child are struggling to breathe or have severe shortness of breath then you do need to get emergency care,” said Melnick.
The is no vaccine yet for RSV, which is especially hard on young children. That, along with the other illnesses, has both Doernbecher at OHSU and Legacy's Randall Children's Hospital at crisis standards of care.
“Our two pediatric hospitals are in crisis care, which allows them to be more flexible with staffing and space in order to not turn away patients or have to limit interventions for patients, but it's a sign of real distress in our hospitals and health systems across the board that I am genuinely concerned is going to get worse before it gets better,” said Dr. Jennifer Vines, Multnomah County health officer.
Vines also strongly encourages vaccinations as a way to avoid or lesson the effects of illness. And RSV is a virus that survives on surfaces, so it's important to wipe things down and wash your hands well.
Dr. Vines added that as much as people may not want to hear it, she recommends wearing masks inside public places until this situation passes. And for those at high risk, it's best to avoid public gatherings as much as possible.
Click here more information from Multnomah County on managing seasonal illnesses.
State data updated Wednesday shows the number of reported flu and COVID-19 cases in North Carolina increased over the last week.
Credit: auremar - stock.adobe.com
It’s not even the height of the typical flu season yet, but many people have already caught a respiratory virus.
“We’ve seen an increase in flu, we’ve seen an increase in strep, ear infections, some RSV, COVID is still going around,” Natalie Anderson, the pharmacist at Dilworth Drug and Wellness Center, said.
Doctors’ offices and hospitals across the region are slammed with patients. Statewide, the number of emergency department visits for flu-like illness is way up compared to the same time in the past two years.
“We are seeing higher rates of flu now as compared to both during the COVID pandemic and even the years prior to the COVID pandemic,” Dr. Ward Adcock, the Vice President of Medical Affairs at CaroMont Health, said.
At CaroMont Health in Gaston County, the number of flu admissions hasn’t been this high since 2009. Adcock said the number of flu cases will likely rise over the next two to three months.
“I would urge anyone if you haven’t been vaccinated yet to please go out and get vaccinated because that’s the best way to prevent the flu,” he said. “And we’re seeing already that this year’s flu vaccine is very effective.”
Compounding the stress, pharmacists across the country are having a hard time keeping their shelves stocked with certain antibiotics and antivirals, including Tamiflu.
“We’ve had a huge challenge being able to get antibiotics like amoxicillin, Augmentin, that turned into a decrease in the ability to get Tamiflu too in the last couple of weeks," Anderson said. "And these are things that people need right away not that they can wait on."
Pharmacists at Dilworth Drug and Wellness Center are taking whatever allocations they can get, using new suppliers and in some cases, working with doctors on alternative treatments.
“I can’t really pinpoint a time when I couldn’t get Tamiflu and there’s like zero available," Anderson said. "Now that they’ve had some allocations this week, we were able to get six one day but especially with the pediatric population, sometimes we have to use two or three bottles just for one patient so that doesn’t really go far."
With the stress on the healthcare system, doctors say this year more than ever it’s important to take as many preventative steps as possible. It is not too late to get vaccinated and doctors stress people shouldn’t put it off any longer.
“If you were thinking I’ll just maybe take Tamiflu if I happen to get flu this season, that may not work out because there may not be availability in the outpatient pharmacy,” Adcock said.
Hand washing and staying home when sick are also important.
A accurate study published in the journal Trends in Molecular Medicine reviewed the current efforts in developing nasal vaccines, delivery systems, and clinical applications for preventing respiratory illnesses.
Review: Nasal vaccines: solutions for respiratory infectious diseases. Image Credit: Josep Suria / Shutterstock
Mucosal surfaces are exposed to external environments and serve as primary entry sites for foreign antigens. Thus, they have a unique immune system that is independently regulated, which acts as the first barrier against foreign substances. Mucosal vaccines leverage this unique system and have been in the limelight due to the coronavirus disease 2019 (COVID-19) pandemic.
Though intramuscularly (IM) administered mRNA vaccines have been effective, they fail to elicit mucosal immunity efficiently. In contrast, mucosal vaccines induce systemic responses at par with IM-administered vaccines and trigger responses at mucosal surfaces. As a result, mucosal vaccination can protect against infection and severe illness. In addition, mucosal immune responses are generally induced at antigen delivery/administration sites.
Multiple administration sites have been considered for mucosal vaccines, such as oral, vaginal, rectal, and nasal mucosa. Nasal administration elicits effective responses in the reproductive and respiratory tracts through the lymphocyte-homing pathway. Therefore, it is suggested as an effective and logical means to prevent respiratory and sexually-transmitting infections, including COVID-19.
Nasopharyngeal-associated lymphoid tissue (NALT) is a primary site of immune induction for vaccines and invading pathogens. NALT contains B, T, and antigen-presenting cells (APCs) and is covered by a layer of microfold cells, specialized cells for antigen uptake. APCs phagocytose the absorbed antigens, process and present them to naïve T cells.
Stimulated T lymphocytes produce interleukin (IL)-5 and transforming growth factor (TGF)-β for B cell activation. Then, B cells differentiate into immunoglobulin (Ig) A-positive (IgA+) B cells. The antigen-specific T and IgA+ B cells traverse to effector sites, where the IgA+ B cells terminally differentiate into plasma cells producing IgA.
The plasma cell-produced polymeric or dimeric IgA binds to the polymeric Ig receptor on epithelial cells and is transported as secretory IgA (sIgA) into the nasal cavity lumen. sIgA is pivotal in mucosal immunity for capturing upper respiratory tract pathogens and preventing adhesion to mucosal surfaces.
A critical feature of acquired immune responses is the induction of immunologic memory for long-term immunity against infection. Tissue-resident memory cells remain in non-lymphoid mucosal tissues without entering circulation for long periods. These cells are activated upon re-exposure to antigens and promptly induce effector functions.
Mucosal tissues have mechanisms to exclude foreign particles, which may prevent the efficient delivery of vaccine antigens. Therefore, a delivery vehicle that can circumvent this obstacle is necessary. To this end, non-replicating and replicating delivery systems have been developed. Replicating systems involve recombinant viral vectors that multiply in the host and deliver vaccine antigens continuously.
Besides viruses, bacteria-based delivery systems have been investigated. Specifically, Lactobacillus, a relatively safe organism, is a leading candidate for vaccine delivery due to its ability to deliver vaccine antigens directly to the nasal mucosa. Although effective in inducing humoral and cellular responses, the safety concerns of replicating delivery systems, such as the toxic effects of vectors and the reversion to virulence, need to be addressed before these systems can advance in clinical use.
Non-replicating delivery systems, such as non-replicating viral vectors, polymers, nanomaterials, and liposomes, have been developed to overcome the safety issues associated with replicating designs. Adenoviral vectors are promising as they do not require adjuvant co-administration. Nanomaterials have been extensively studied as vaccine delivery vehicles due to biological affinity and safety advantages.
Eleven nasal vaccine candidates are being tested in clinical trials, per the World Health Organization’s COVID-19 vaccine tracker. The replication-competent influenza virus vector-borne vaccine based on the spike protein’s receptor-binding domain is in a Phase 3 trial. Non-replicating vector-borne vaccines under various clinical trial stages include CVXGA1-001, BBV154, and Covishield.
COVI-VAC, a live-attenuated vaccine under phase 3 evaluation, has improved safety due to the deletion of the furin cleavage site and the recoding of spike segments. The MV-014-212 vaccine, based on the spike protein, uses a live-attenuated respiratory syncytial virus (RSV) vector and is evaluated in a phase 1 trial for safety and immunogenicity. Besides vector- and live-attenuated virus-based vaccines, three recombinant protein subunit-based nasal vaccines, CIGB-669, Razi Cov Pars, and ACM-001, are under development.
FluMist Quadrivalent is the only nasal influenza vaccine approved by the United States (US) Food and Drug Administration (FDA). Even if a cold-adapted attenuated vaccine could be developed by decreasing virulence, it will not be approved for use in older adults and infants, as nasal administration of live vaccines can result in medically significant wheezing.
Another critical concern is the reversion to the replicative state of vaccines using the whole pathogen. As such, recombinant protein subunit-based vaccines appear safer than live vaccines. Nevertheless, recombinant antigens require delivery systems and tend to induce weak responses, warranting co-administration of adjuvants as immunostimulants. For example, an inactivated nasal influenza vaccine was used in Switzerland in the past but was terminated due to several cases of facial nerve palsy.
Furthermore, another inactivated nasal influenza vaccine (Pandemrix) increased the risk of narcolepsy. Nasally administered substances may traverse into the brain via the olfactory epithelium and bulbs, potentially affecting neural functions. Because of the nasal cavity’s proximity to the central nervous system (CNS), nasal vaccine candidates must be tested before clinical application to ensure that vaccine components do not affect the CNS.
Nasal vaccines can elicit antigen-specific systemic and mucosal immune responses and are considered viable alternatives to IM vaccines, given their efficacy and ease of administration. However, only a few nasally administered vaccines are in use currently. A concerted global effort to develop safe and effective nasal vaccines is necessary to combat the COVID-19 pandemic and the threat of pandemics in the future.