Gail Connor Roche

Influenza (flu) vaccine stored up to 12 years as part of the US Department of Health and Human Services’ pandemic readiness plan is safe and immunogenic, a 

The H5N1 avian influenza antigen and adjuvant maintained their functional integrity in the National Pre-Pandemic Influenza Vaccine Stockpile (NPIVS), according to testing led by Rick Bright, PhD, director of the Biomedical Advanced Research and Development Authority (BARDA).

BARDA was established as part of HHS to help secure the US from pandemic influenza, among other threats.

“Our goal was to build and maintain a stockpile of vaccines for emerging influenza viruses considered to be high risks to public health,” Bright told 

®. “The study results mean that if a particular type of influenza, H5N1, became a pandemic, clinicians and the public can feel confident that this vaccine is safe and provides some protection from the viral infection.”

BARDA began pre-pandemic influenza vaccine procurement in 2005 for vaccines that would provide protection against emerging avian influenza H5N1 viruses posing a significant pandemic threat. The antigen and adjuvant components are stored in refrigerated in bulk containers at the influenza vaccine manufacturers’ FDA-approved facilities.

The team focused on the strain that, at the time, had the highest risk of causing severe sickness and death in humans if it were to become easily transmissible from person to person, Bright said.

The vaccine used for the study was developed from the A/Viet Nam/1203/2004 (H5N1) virus.

“It was produced using the same methods as the FDA-approved seasonal influenza vaccines.” Bright said. “However, seasonal vaccines are stored for 1 year or less, and the H5N1 vaccine has been stored since 2005.”       

To test the efficacy and safety of the stored vaccine components, investigators conducted a randomized, double-blinded phase 2 trial that considered the oldest stockpiled influenza A(H5N1) antigen, stored over the previous 10—12 years, with and without&#8239;and an adjuvant that had been stored over the previous 2–7&#8239;years.

More than 400 healthy adults aged 18-49 years old were enrolled at 6 US clinical sites between March 2016 and April 2017. The study then tested how well 2 doses of vaccine, designed to protect against a single virus strain, stimulated their immune systems and how well the vaccine was tolerated.

“We measured whether vaccinated people developed antibodies that block the ability of H5N1 virus to infect cells in a test tube,” Bright said. Vaccinated people who have enough of such antibodies in the blood are likely to be protected from viral infection or severe illness.

The study also looked for potential adverse events. The most common symptoms were injection site pain, headache, fatigue, and myalgia.

Investigators reported the stockpiled vaccines were tolerable, adverse events were generally mild, and patients reported no drop in immunogenicity to the oldest vaccine. VN1203 vaccine was also more effective when combined with an adjuvant known as MF59.

“Without adjuvants, vaccines for influenza viruses like H5N1 often required a large amount of antigen to stimulate the desired levels of antibodies,” Bright said.

 By adding adjuvant, the researchers decreased the amount of antigen needed—by 12 to 24 times&mdash;to produce an immune response as they also increased the ability to block viruses that have some mutations.

“That’s a significant difference and will allow the antigen to be used to vaccinate more people if an H5N1 pandemic occurs,” Bright noted.

Since 2005, the rapid mutation of H5N1 viruses has sparked the stockpiling of other vaccines. Bright noted that, in 2014, BARDA added vaccine against the H7N9 avian flu virus that emerged in China.

Regarding the H5N1 vaccine, Bright noted that up to 20 million people could be vaccinated with it—including healthcare workers, law enforcement officers, and first responders.

Bright said his team has worked with the private sector using such technologies.

“As new influenza strains emerge and infect people, we will continue to work with private industry to make antigens against them in case vaccines would be needed,” he said.

In the meantime, BARDA will continue to test and monitor the vaccines in the NPIVS.

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The National Pre-Pandemic Influenza Vaccine Stockpile has been storing vaccines for particular pandemic-potential viruses since 2005.

Flu Vaccine Stored for Pandemic Risk Found Safe, Immunogenic

 vaccine shot may reduce the severity of the infection, even when the vaccine doesn’t prevent the influenza virus itself, a recent study evidenced.

The finding is especially important for people aged 65 years and over. These individuals experience up to 90% of flu-related deaths and more than half of flu-related hospitalizations. According to the most recent weekly flu report from the US Centers for Disease Control and Prevention (CDC), more than 900 elderly people in the US have reported influenza positive specimens thus far this flu season.

In a study conducted in northeast Spain, investigators from the University of Barcelona and public health agencies there found that the effectiveness of a flu shot to prevent intensive care unit (ICU) admissions or death in people 65 and older was 44% out of the total patients hospitalized for flu.

The vaccine’s effectiveness in preventing ICU admissions or death overall was 23%, data from 12 hospitals showed.

“This study, based on surveillance of hospitalized cases of severe laboratory-confirmed influenza from 2010/11—2015/16 in Catalonia, showed an effectiveness of influenza vaccination in reducing ICU admission or death of 23%,” investigators wrote.

Most patients hospitalized for severe influenza are in the 65-and-up age group. Many have underlying medical conditions that lead to a higher risk of influenza-associated complications, ICU admission, and death, investigators noted.

“Influenza vaccination could reduce ICU admission and death in these patients, by reducing the severity of the disease,” they said.

While flu shots are effective in preventing visits to primary care doctors and admissions to the hospital, chronic conditions and risk factors such as older age may hinder a successful vaccine response.

But studies diverge when it comes to assessing the effectiveness of the vaccine in reducing the most severe effects of the flu: ICU admissions and death of patients whose vaccine did not prevent them from getting infected.

The CDC reported in August that a study it supported showed flu shots lessened the risk of severe influenza among adults, including hospitalizations and admissions to the ICU. Vaccination also reduced the severity of the illness.

In that study, adults who were vaccinated decreased their risk of being admitted to the hospital with flu and placed in a general ward bed by 37%. A flu shot was even more effective in preventing the most severe forms of flu. It reduced the risk of being admitted to an ICU with flu by 82%.

The CDC noted at the time that, while the annual flu vaccination varies in efficacy, it remains the best possible prevention of the flu and its potentially severe consequences.

In the current study, the researchers considered 1727 patients age 18 and older who were hospitalized for flu in the Catalan region of Spain over 6 flu seasons ending in 2016.

Of this group, 591 (34.2%) were admitted to the ICU and 223 (12.9%) died.

A total of 1285 (74.4%) of the patients presented&thinsp;with one or more influenza risk factors, but only 450 (26.1%) had received the influenza vaccine. Except for 1 season (2013/14), the vaccine had a positive effect, although the effect was not significant in some seasons, the team found.

This suggests an important potential impact of vaccination in reducing influenza severity.

“Influenza vaccination is a factor for a good prognosis, as it reduces influenza-associated disease severity in patients, in whom vaccination did not prevent influenza,” investigators wrote.

One explanation for these results is the role the immune system plays in the influenza virus.

“People who were previously infected by the virus or who received anti-influenza vaccines would get benefits, at least, in the pre-existing cross-reactive memory of cytotoxic T lymphocytes, which would reduce the severity of the infection, even without protective antibodies,” investigators noted.

Influenza vaccine effectiveness in reducing severe outcomes over six influenza seasons, a case-case analysis, Spain, 2010/11 to 2015/16

In a recent Spain-based study, patients who received the annual vaccination were 82% less likely to be hospitalized by the flu.


Flu Vaccine Reduces Virus Severity in Patients, Regardless of Prevention

Pregnant women who are seriously ill with 

 are more likely to deliver babies with complications than those without the flu or with milder cases, a study that considered more than 3000 pregnancies has found.

“Severely ill women with 2009 H1N1 influenza during pregnancy were more likely to have adverse birth outcomes, such as their baby being born preterm or of low birth weight than women without influenza,” lead author Kimberly Newsome, MPH, BSN, a health scientist at the US Centers for Disease Control and Prevention’s (CDC’s) National Center on Birth Defects and Developmental Disabilities told 

The investigators also discovered that the severity of the mother’s flu plays a role in her baby’s outcome.

Pregnant women with the flu who were not hospitalized and those who were hospitalized, but not admitted to intensive care, delivered infants that did not face significantly elevated risks for complications, the team wrote in 

“We don’t know why only severely ill women had adverse birth outcomes,” Newsome said. “It suggests that it isn’t the flu virus per se, but the severe illness associated with influenza that results in problems at birth.”

Many studies have demonstrated the risks that influenza poses to pregnant women, but information on infant outcomes is limited.

To investigate, a team from the CDC collaborated with health departments in California, New York City, North Carolina, Utah, and Washington. The investigators reviewed the records of 490 pregnant women with confirmed or probable 2009 H1N1 influenza—the predominant type of influenza circulating in the current flu season.

“We chose the year 2009 because that was the year of the H1N1 pandemic, when large numbers of women became ill with the flu,” Newsome said. “We would expect that the findings of our study would apply to other years and other types of flu.”

The investigators then compared the women with the flu to 1451 women who were pregnant in the same year, but didn’t have the virus as well as 1446 women with pregnancies in the prior year who also didn’t have influenza.

“We collected data from birth certificates on babies whose moms didn’t have the flu, which allowed for a comparison group, something that wasn’t available in many previous studies,” Newsome said.

The data showed that 64 women with 2009 H1N1 influenza were admitted to an ICU. These mothers were more likely to deliver infants who were born at less than 37&thinsp;weeks of gestation. The babies also had low birth weight, and Apgar scores—a measure of how the infant is doing at birth&mdash;of 6 or less at 5 minutes when compared to the newborns of women who did not have influenza.

Babies born to mothers with the flu who didn’t go to the hospital or were not sick enough for the ICU also did not have significantly elevated risks for infant complications, the data showed.

“No statistical differences in infant outcomes were found among women in the comparison groups and women with 2009 H1N1 influenza who were admitted to the hospital but not ICU or not admitted to the hospital,” the investigators wrote.

As for timing, the team found that poor infant outcomes might occur if a woman delivered either after or during a flu infection. However, the complications were more common among those who gave birth while they had the flu, Newsome said.

The study, like others, reinforces the CDC’s recommendation that everyone 6 months and older should get an annual flu shot. This is especially true during pregnancy — for both the mother and her infant.

“Newborn babies are at increased risk of becoming severely ill with influenza, but can’t receive a flu shot until they are 6 months of age,” Newsome said. “Getting a flu shot during pregnancy helps protect both the mother and her baby.”

When a pregnant woman gets a flu shot, the antibodies that she makes pass across the placenta and can protect her baby from getting the flu, making the shot effective and safe for bother the mother and her baby.

“Pregnant women and those who might be considering pregnancy can reduce their health risks and risks to their infants by getting a flu shot and getting prompt treatment with antiviral medications if they get sick,” Newsome stressed.

Outcomes of infants born to women with influenza A(H1N1)pdm09

Investigators also discovered that the severity of the mother’s flu plays a role in her baby’s outcome.

Severe Flu in Pregnant Women Linked to Poor Outcomes in Newborns

A flu shot was more effective than nasal spray in protecting children aged 2 to 17 years old against a widely circulating type of 

, according to a recent study that included more than 17,000 young people from 42 US states.

To reach that conclusion, investigators looked to previously reported data from

5 US studies that covered the influenza seasons from 2013-2014 through 2015-2016.

These studies considered the viral effectiveness (VE) of inactivated influenza vaccine (IIV), administered as a shot, and quadrivalent live attenuated vaccine (LAIV4), delivered as a nasal spray known as FluMist.

The current mega-analysis mirrored previous results. Investigators reported 67% effectiveness for the IIV shot versus 20% effectiveness for the LAIV4 spray against influenza A/H1N1pdm09, the main type of flu in the US this season.

“The findings of lower effectiveness of LAIV compared to IIV against A/H1N1pdm09 virus in the US are consistent with the findings from the individual studies,” lead author Jessie R. Chung, MPH, an epidemiologist in the US Centers for Disease Control and Prevention’s (CDC’s) Influenza Division, told 

When the team analyzed the 2 vaccines’ effectiveness against any type of influenza, the difference was less pronounced: 51% VE for IIV and 26% for LAIV4

 The study also suggested a possible but non-significant benefit of LAIV4 over IIV against influenza B viruses.

“The vaccines provided similar protection against A (H3N2) and B viruses,” Chung said.

The US Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) recommended against using the nasal spray for young children in the 2016—17 and 2017–18 flu seasons because of concerns about its earlier effectiveness

However, Chung noted that LAIV has been updated since then.

The spray was used in Europe and Canada in 2017—2018, although limited circulation of the A/H1N1pdm09 virus hindered the ability to obtain precise effectiveness estimates. According to information from the UK though, the US can expect more favorable results.

“VE estimates against H1N1 last season in the UK are encouraging and suggest effectiveness of LAIV against that virus in the US will be higher this season,” Chung said.

The ACIP has reinstated the recommendation for use of LAIV4 in the US for the current influenza season as 1 vaccine choice. The AAP recommends the inactivated influenza vaccine as the primary choice for all children because of past effectiveness questions and lack of current data on LAIV4.

However, the AAP said LAIV4 may be offered for children who would not otherwise receive an influenza vaccine, and for whom it is appropriate by age and health status, according to its website.

“LAIV is again an option for this season for patients aged 2-49 years who would prefer to receive the nasal spray vaccine,” Chung said. Influenza vaccinations can reduce the risk of flu-associated hospitalization and can be life-saving in children, she stressed.

“Parents should know that the most important thing they can do to protect their child against influenza is to vaccinate him or her,” she said.  

She added that the CDC recommends annual influenza vaccination for everyone 6 months and older with any licensed, age-appropriate flu vaccine (IIV, RIV4, or LAIV4) with no preference expressed for any 1 vaccine over another.   

RIV4 is a recombinant egg-free vaccine known as Flublok Quadrivalent, which is delivered as a shot to adults aged 18 years and older, according to the CDC.

While the new vaccine effectiveness analysis drew similar conclusions to the 5 individual studies, Chung noted that the latest investigation provided more depth.

“The current study better described vaccine effectiveness in age groups that the individual studies were not able to due to small sample sizes,” she said. 

Live Attenuated and Inactivated Influenza Vaccine Effectiveness

Analysis of past studies shows benefit of inactivated influenza vaccine against A/H1N1pdm09 virus in 2- to 17-year-olds. 
 

Gail Connor Roche

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