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Study indicates need for developing mucosal vaccines to induce potent immune responses at sites where SARS-CoV-2 infection occurs

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In a recent study published in Clinical Infectious Diseases, a team of researchers measured the antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from nasal fluid, saliva, and plasma to compare the antibody levels between blood and mucosal fluids.

Study: Comparison of levels of nasal, salivary, and plasma antibody to SARS-CoV-2 during natural infection and after vaccination. Image Credit: TG23/Shutterstock

Background

SARS-CoV-2 is known to enter the body through mucosal surfaces such as the nasal passages. However, most studies examining the level of protection against SARS-CoV-2 infections have measured the antibody levels in blood samples, and few have evaluated the antibody levels in mucosal fluids such as nasal secretions.

Given that SARS-CoV-2 infections largely occur in mucosal tissue, the antibody levels in nasal fluids and saliva might not correlate with those in blood. Furthermore, the antibodies in the mucosa could result from antibody transudation from the plasma or the production of antibodies by plasma cells in the mucosa. Determining the differences in antibody levels in mucosal fluids and blood could aid the development of mucosal vaccines against SARS-CoV-2.

About the study

In the present study, the team longitudinally measured the antibody levels in the nasal fluid, saliva, and plasma of individuals infected with SARS-CoV-2 before and after vaccination and vaccinated individuals who had not been infected with SARS-CoV-2. The participants comprised healthcare workers and other employees at the National Institutes of Health in Bethesda, Maryland, in the United States. The study was conducted between April 2020 and February 2022.

Blood samples were collected monthly from healthcare workers who came in contact with patients. Nasal fluid and saliva samples were also collected from the participants. The luciferase immunoprecipitation systems (LIPS) assay was performed to measure the anti-SARS-CoV-2 spike and nucleocapsid antibodies. Since immunoglobulin A (IgA) antibodies play an important role in mucosal immunity, IgA-specific antibody levels were also measured in the nasal fluid and saliva samples.

Results

The results reported that the levels of anti-nucleocapsid antibodies against SARS-CoV-2 declined faster than the anti-spike protein antibodies in the plasma samples of unvaccinated infected individuals. Vaccination increased the anti-spike antibody levels in the plasma, while the level of anti-nucleocapsid antibodies remained the same. The anti-spike antibody levels in the nasal fluid decreased faster than in plasma.

In vaccinated individuals who were not infected with SARS-CoV-2, the anti-spike antibodies in nasal fluid and saliva and the IgA-specific antibodies in the nasal fluid decreased faster than those in plasma. Furthermore, the increase in antibody levels after vaccination in individuals with previous SARS-CoV-2 infections varied across the plasma, saliva, and nasal fluid samples. While one vaccine dose resulted in a 22.4-fold increase in anti-spike antibodies in plasma, nasal fluid and saliva only exhibited an increase of 14.1 and 12.3-fold, respectively.

In unvaccinated, infected individuals, the anti-spike antibody levels in the nasal fluids and saliva correlated with that in the plasma, while the anti-nucleocapsid antibody levels did not, suggesting that the mucosal antibodies were most likely a result of transudation from plasma and were not produced by plasma cells in the mucosa. The authors believe that the rapid decline of mucosal antibody levels after the second vaccine dose as compared to the antibody levels in plasma might explain the increase in breakthrough infections despite high antibody levels in the blood.

Furthermore, intramuscular administration of the SARS-CoV-2 vaccine might be responsible for the lower and short-lived antibody levels in mucosal tissue. Vaccines given through the oral or intranasal route might produce stronger mucosal immunity against SARS-CoV-2. Oral poliovirus vaccines and intranasal influenza vaccines have shown better protection against disease than intramuscularly administered vaccines.

Furthermore, experiments with animal models have shown that intranasal vaccinations against SARS-CoV-2, as well as SARS-CoV-1 and Middle East respiratory syndrome (MERS), have been more effective than intramuscular vaccines.

Conclusions

To summarize, the study measured the antibodies against SARS-CoV-2 spike and nucleocapsid proteins in plasma, saliva, and nasal fluid samples of individuals infected with SARS-CoV-2 before and after vaccinations, as well as SARS-CoV-2-naive, vaccinated individuals.

The results suggested that in unvaccinated, infected individuals, the anti-spike antibody levels in nasal fluid and saliva correlated with that in plasma, indicating the transudation of antibodies from blood to mucosa. Anti-nucleocapsid antibody levels in saliva, nasal fluid, and plasma declined rapidly compared to anti-spike antibody levels.

Furthermore, vaccinations did not boost the antibody levels in nasal fluids and saliva to the same extent as in plasma, suggesting that intramuscularly administered vaccines might not be effective in increasing mucosal immunity. The results highlight the importance of developing orally and intranasally administered vaccines against SARS-CoV-2.

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Canada to donate up to 200,000 vaccine doses to combat mpox outbreaks in Africa

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The Canadian government says it will donate up to 200,000 vaccine doses to fight the mpox outbreak in Congo and other African countries.

It says the donated doses of Imvamune will come from Canada’s existing supply and will not affect the country’s preparedness for mpox cases in this country.

Minister of Health Mark Holland says the donation “will help to protect those in the most affected regions of Africa and will help prevent further spread of the virus.”

Dr. Madhukar Pai, Canada research chair in epidemiology and global health, says although the donation is welcome, it is a very small portion of the estimated 10 million vaccine doses needed to control the outbreak.

Vaccine donations from wealthier countries have only recently started arriving in Africa, almost a month after the World Health Organization declared the mpox outbreak a public health emergency of international concern.

A few days after the declaration in August, Global Affairs Canada announced a contribution of $1 million for mpox surveillance, diagnostic tools, research and community awareness in Africa.

On Thursday, the Africa Centres for Disease Control and Prevention said mpox is still on the rise and that testing rates are “insufficient” across the continent.

Jason Kindrachuk, Canada research chair in emerging viruses at the University of Manitoba, said donating vaccines, in addition to supporting surveillance and diagnostic tests, is “massively important.”

But Kindrachuk, who has worked on the ground in Congo during the epidemic, also said that the international response to the mpox outbreak is “better late than never (but) better never late.”

“It would have been fantastic for us globally to not be in this position by having provided doses a much, much longer time prior than when we are,” he said, noting that the outbreak of clade I mpox in Congo started in early 2023.

Clade II mpox, endemic in regions of West Africa, came to the world’s attention even earlier — in 2022 — as that strain of virus spread to other countries, including Canada.

Two doses are recommended for mpox vaccination, so the donation may only benefit 100,000 people, Pai said.

Pai questioned whether Canada is contributing enough, as the federal government hasn’t said what percentage of its mpox vaccine stockpile it is donating.

“Small donations are simply not going to help end this crisis. We need to show greater solidarity and support,” he said in an email.

“That is the biggest lesson from the COVID-19 pandemic — our collective safety is tied with that of other nations.”

This report by The Canadian Press was first published Sept. 13, 2024.

Canadian Press health coverage receives support through a partnership with the Canadian Medical Association. CP is solely responsible for this content.

The Canadian Press. All rights reserved.

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How many Nova Scotians are on the doctor wait-list? Number hit 160,000 in June

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HALIFAX – The Nova Scotia government says it could be months before it reveals how many people are on the wait-list for a family doctor.

The head of the province’s health authority told reporters Wednesday that the government won’t release updated data until the 160,000 people who were on the wait-list in June are contacted to verify whether they still need primary care.

Karen Oldfield said Nova Scotia Health is working on validating the primary care wait-list data before posting new numbers, and that work may take a matter of months. The most recent public wait-list figures are from June 1, when 160,234 people, or about 16 per cent of the population, were on it.

“It’s going to take time to make 160,000 calls,” Oldfield said. “We are not talking weeks, we are talking months.”

The interim CEO and president of Nova Scotia Health said people on the list are being asked where they live, whether they still need a family doctor, and to give an update on their health.

A spokesperson with the province’s Health Department says the government and its health authority are “working hard” to turn the wait-list registry into a useful tool, adding that the data will be shared once it is validated.

Nova Scotia’s NDP are calling on Premier Tim Houston to immediately release statistics on how many people are looking for a family doctor. On Tuesday, the NDP introduced a bill that would require the health minister to make the number public every month.

“It is unacceptable for the list to be more than three months out of date,” NDP Leader Claudia Chender said Tuesday.

Chender said releasing this data regularly is vital so Nova Scotians can track the government’s progress on its main 2021 campaign promise: fixing health care.

The number of people in need of a family doctor has more than doubled between the 2021 summer election campaign and June 2024. Since September 2021 about 300 doctors have been added to the provincial health system, the Health Department said.

“We’ll know if Tim Houston is keeping his 2021 election promise to fix health care when Nova Scotians are attached to primary care,” Chender said.

This report by The Canadian Press was first published Sept. 11, 2024.

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Newfoundland and Labrador monitoring rise in whooping cough cases: medical officer

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ST. JOHN’S, N.L. – Newfoundland and Labrador‘s chief medical officer is monitoring the rise of whooping cough infections across the province as cases of the highly contagious disease continue to grow across Canada.

Dr. Janice Fitzgerald says that so far this year, the province has recorded 230 confirmed cases of the vaccine-preventable respiratory tract infection, also known as pertussis.

Late last month, Quebec reported more than 11,000 cases during the same time period, while Ontario counted 470 cases, well above the five-year average of 98. In Quebec, the majority of patients are between the ages of 10 and 14.

Meanwhile, New Brunswick has declared a whooping cough outbreak across the province. A total of 141 cases were reported by last month, exceeding the five-year average of 34.

The disease can lead to severe complications among vulnerable populations including infants, who are at the highest risk of suffering from complications like pneumonia and seizures. Symptoms may start with a runny nose, mild fever and cough, then progress to severe coughing accompanied by a distinctive “whooping” sound during inhalation.

“The public, especially pregnant people and those in close contact with infants, are encouraged to be aware of symptoms related to pertussis and to ensure vaccinations are up to date,” Newfoundland and Labrador’s Health Department said in a statement.

Whooping cough can be treated with antibiotics, but vaccination is the most effective way to control the spread of the disease. As a result, the province has expanded immunization efforts this school year. While booster doses are already offered in Grade 9, the vaccine is now being offered to Grade 8 students as well.

Public health officials say whooping cough is a cyclical disease that increases every two to five or six years.

Meanwhile, New Brunswick’s acting chief medical officer of health expects the current case count to get worse before tapering off.

A rise in whooping cough cases has also been reported in the United States and elsewhere. The Pan American Health Organization issued an alert in July encouraging countries to ramp up their surveillance and vaccination coverage.

This report by The Canadian Press was first published Sept. 10, 2024.

The Canadian Press. All rights reserved.

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