Story at-a-glance

• A cell-based flu vaccine, Flucelvax, grown in dog kidney cells became available during the 2017 to 2018 flu season
• Flucelvax, made by Seqirus, was supposed to offer advantages over egg-based flu vaccines, which are notoriously problematic
• A study by the U.S. Food and Drug Administration (FDA) revealed the cell-based vaccine worked only a little bit better than the conventional flu shot in protecting seniors — which isn’t saying much
• While flu vaccines overall had only 24 percent effectiveness in preventing flu-related hospitalizations in people aged 65 and older, the Flucelvax vaccine had an effectiveness rate of only 26.5 percent in that population

Most flu vaccines in the U.S. are grown in chicken eggs, but during the 2017 to 2018 flu season, a cell-based flu vaccine, Flucelvax, grown in dog kidney cells became available. This vaccine was licensed in 2012 and is approved for individuals aged 4 years and over. As the effectiveness of conventional flu shots continues to leave much to be desired, the new Flucelvax vaccine was touted as a new-and-improved version that would protect more people once flu season hit.

In reality, a study by the U.S. Food and Drug Administration (FDA) revealed the shot worked only a little bit better than the conventional flu shot in protecting seniors — which isn’t saying much. While flu vaccines overall had only 24 percent effectiveness in preventing flu-related hospitalizations in people aged 65 and older, the Flucelvax vaccine had an effectiveness rate of only 26.5 percent in that population.1

Flu Shot Grown in Kidney Cells No Better Than Flu Shot Grown in Eggs

Flucelvax, made by Seqirus, was supposed to offer advantages over egg-based flu vaccines, which are notoriously problematic. Because the egg-based vaccines must adapt while grown in eggs, they often acquire mutations that can hamper their effectiveness.2 In addition, according to Seqirus, the cell-cultured vaccine is superior because it doesn’t rely on egg availability, which could be affected by avian flu, and is grown in closed sterile bioreactors instead of in an open system.

Further, the manufacturing technology eliminates the need for antibiotics, which are sometimes used in egg-based vaccines manufacturing, and could potentially be rapidly produced during an outbreak or pandemic (whereas egg-based vaccines have only limited ability to respond to such demands).3 However, the end product failed to deliver where it matters most: effectiveness.

In March 2018, FDA Commissioner Scott Gottlieb announced that preliminary FDA data suggested Flucelvax worked about 20 percent better than the conventional egg-based vaccine. However, the final data suggested an even smaller benefit.

FDA analysts looked at medical records from 16 million people aged 65 and older covered by Medicare, including flu shots received and whether they ended up in the hospital due to the flu. As mentioned, the effectiveness of both vaccines was similar: 24 percent for the egg-based flu vaccine and 26.5 percent for the cell-based Flucelvax.

Why Egg-Based Vaccines Failed, and Cell-Based Vaccines May Be No Better

It’s been known for some time that growing flu vaccines in eggs may lead to problematic mutations that make them less effective against circulating flu viruses. Such was the case during the 2016 to 2017 flu season, when H3N2 viruses were prevalent. Writing in PNAS, researchers noted, “Human vaccine strains grown in eggs often possess adaptive mutations that increase viral attachment to chicken cells.”

They identified a mutation in the flu vaccine strain that produced antibodies that didn’t work well to neutralize the H3N2 viruses circulating that year.4 “These studies highlight the challenges associated with producing influenza vaccine antigens in eggs, while offering a potential explanation of why there was only moderate vaccine effectiveness during the 2016–2017 influenza season,” they noted. Likewise, according to a NEJM report:

“During the egg-based production process, the vaccine virus acquires amino acid changes that facilitate replication in eggs, notably changes in the hemagglutinin (HA) protein that mediates receptor binding. Since the influenza HA is the primary target of neutralizing antibodies, small modifications in this protein can cause antigenic changes in the virus and decrease vaccine effectiveness.

Egg adaptation has been postulated to contribute to low vaccine effectiveness, particularly with influenza A (H3N2) viruses [the type predicted to be most widely circulating this year].”5

Studies have repeatedly shown that flu shots have been from zero to less than 50 percent effective in preventing type A or B influenza over the past decade.6 Again during the 2017 to 2018 flu season, the U.S. Centers for Disease Control and Prevention (CDC) estimated the flu vaccine’s effectiveness to be only 25 percent against the H3N2 virus.7 The idea that cell-based vaccines would provide an answer to this problem, particularly among H3N2 strains, now appears to be overly optimistic.

Dr. John Treanor, a flu vaccine expert at the University of Rochester Medical Center, told STAT News in 2017, “There wasn’t convincing evidence that it [cell culture flu vaccine] was better so why would anyone spend extra money to buy that? … The business case was tough, and I think a lot of these enterprises did not make it partially because of that.”8 This was before the FDA data came in on the 2017 to 2018 season, which offered proof that the effectiveness was virtually identical to the conventional egg-based version.

Your Immune System’s Response to Flu Vaccine Can Make You More Susceptible to the Flu

The flu vaccine is described as the best tool to stay healthy during flu season despite years of dismal failure. There are many reasons why flu vaccines are often ineffective, starting with vaccine mismatches. Each year, health officials make educated guesses as to which influenza strains will be circulating in order to include them in that year’s vaccine. Often, the vaccines are not well matched to circulating viruses.

However, there’s more to it than this, in large part due to the complexity of your immune system and how it works. A term known as heterologous immunity describes the memory your immune system has of previous infections, which it allow it to respond to similar infections later. Sometimes this is a good thing, giving you protection from circulating diseases — but not always. As noted in the Journal of Leukocyte Biology, heterologous immunity has two faces: protection and immunopathology:9

“Immunity to previously encountered viruses can alter responses to unrelated pathogens. This phenomenon, which is known as heterologous immunity, has been well established in animal model systems. Heterologous immunity appears to be relatively common and may be beneficial by boosting protective responses. However, heterologous reactivity can also result in severe immunopathology.”

This may help explain why flu vaccine may offer some level of protection against the viral strains included in the vaccine while simultaneously diminishing your ability to ward off infection by other influenza strains and other types of viral or bacterial infections. The reality is that vaccines may “have nonspecific effects on the ability of the immune system to handle other pathogens,” and these effects have not been evaluated, in large part, according to Trends in Immunology, because “current perception excludes such effects.”10

The strategy of annual flu vaccination may, in fact, be backfiring, leaving those who have been vaccinated annually less protected than those with no prior flu vaccination history.11

Research presented at the 105th International Conference of the American Thoracic Society in San Diego even revealed that children who get seasonal flu shots are more at risk of hospitalization than children who do not. Children who had received the flu vaccine had three times the risk of hospitalization as children who had not. Among children with asthma, the risk was even higher.12

Is Vitamin D a Better Option?

Despite its questionable effectiveness, we’re likely to see more cell-based flu vaccines rolled out. Already, there’s also a flu vaccine produced using genetically modified insect cells and one on the horizon manufactured in Nicotiana benthamiana, a type of tobacco plant known for its ability to make proteins at a high rate of speed.13 Yet, no one knows what the long-term effects of such vaccinations will be, or whether their purported benefits are truly worth the risk.

The Cochrane Collaboration concluded in 2014 that the NNT (number needed to treat) for the flu vaccine is 71.14 In other words, 71 people have to be vaccinated in order for a single case of influenza to be avoided. In a 2017 scientific review, on the other hand, the NNT for vitamin D was 33, meaning one person would be spared from acute respiratory infection such as the flu for every 33 people taking a vitamin D supplement.15

If health and safety were really the chief aim of public health officials, why not promote vitamin D testing and optimization, since vitamin D supplementation has been shown to cut your risk of respiratory infections, including colds and flu, in half if you are vitamin D deficient?16,17

I believe sensible sun exposure is the ideal way to optimize your vitamin D. Taking a vitamin D3 supplement is only recommended in cases when you simply cannot obtain sufficient amounts of sensible sun exposure.

In the latter case, you may need 8,000 IUs of vitamin D3 per day (or more) in order to reach and maintain a clinically relevant level of 40 to 60 nanograms per milliliter (ng/mL). Both vitamin D and sun exposure, by the way, stimulate your immune system,18 which is a key to fighting off all sorts of infections, including the flu.

Focus on Boosting Your Immune System (Especially NK Cells) to Ward Off Flu

Natural killer (NK) cells are a specific type of white blood cell. They’re an important component of your cell-mediated (innate) immune system and are involved in both viral diseases and cancer. Researchers recently discovered that with enough NK cells in your system, you will not contract influenza.19 KLRD1 is a receptor gene found on the surface of NK cells, and the level of KLRD1 found in a person’s blood prior to exposure to the influenza virus was able to predict with 86 percent accuracy whether that individual would contract the flu.

Generally speaking, people whose immune cells consisted of 10 to 13 percent NK cells did not get the flu while those whose levels fell below 10 percent did. NK cells tend to lose functionality as you age, which explains why you may become more susceptible to the flu and other illnesses as you get older. However, you can absolutely counteract this decline and boost your NK cells (no matter what you age), by doing the following — none of which involves getting a flu vaccine:

Get regular exercise

In one study, moderate exercise improved NK cell function in cancer patients.20

Quit smoking

Quitting smoking will also help, as smoking impairs NK cell function.21

Enzymatically modified rice bran (EMRB)

EMRB is produced by exposing rice bran fiber to enzymes isolated from the shiitake mushroom. In one 2013 study, a rice bran product called MGN-322 increased NK cell activity by as much as 84 percent in patients with multiple myeloma after three months of treatment.23 In an earlier study, old mice injected with EMRB had a fivefold increase in NK cell activity within two days.24

Cardamom

A relative of turmeric, known for its potent immune-boosting benefits, cardamom increases NK cell activity.25

Black pepper

Like cardamom, black pepper has also been shown to enhance the cytotoxic activity of NK cells and promote healthy immune function.26

Colostrum

Colostrum is milk produced within the first 24 to 48 hours of giving birth. Colostrum from cows is very similar to human colostrum, and colostrum products are typically derived from cows. The colostrum contains an array of immune and growth factors required by the offspring.

In a 2012 study on mice, oral administration of skimmed and concentrated bovine late colostrum was shown to activate the immune system and protect against influenza infection by boosting NK cell activity.27

Another 2014 animal study concluded that, "Colostrum supplementation enhanced NK cell cytotoxicity and improved the immune response to primary influenza virus infection in mice." Colostrum-supplemented mice that did contract the flu also had less severe infection and a lower viral burden in the lungs compared to controls.28

An earlier study, published in 2007, found treatment with oral colostrum for two months prevented influenza infection three times more effectively than influenza vaccination.29 According to the authors, "Colostrum, both in healthy subjects and high-risk cardiovascular patients, is at least three times more effective than vaccination to prevent flu and is very cost-effective …"

Mushrooms

Mushrooms such as shiitake, maitake and oyster mushrooms, also boost NK cell activity courtesy of beta-glucans, a polysaccharide known for its immune-boosting and cancer-fighting activities.30

Active hexose correlated compound (AHCC)

AHCC is a commercially available fermented mushroom extract that supports healthy immune function, primarily by enhancing NK cell activity. As noted in a paper published in the Natural Medicine Journal:31

“Supplementation studies with AHCC have demonstrated positive effects on immune function in humans and animal models, including decreased tumor formation, increased resistance to viral and bacterial infection; enhanced NK cell activity ...

… increased T-cell proliferation, including altered T-cell activity; altered cytokine production … increased nitric oxide release by peritoneal cells; and antioxidant and anti-inflammatory effects …

Overall, AHCC has been suggested to enhance prognosis and quality of life in a variety of cancers, as well as to elicit potentially positive changes in cytokine production and lymphocyte populations — most notably increased NK cell activity.”

Probiotics

Beneficial bacteria found in traditionally fermented foods also boosts NK cell activity,32 and those with low NK cell levels tend to experience greater benefits from probiotic supplementation than those with healthy levels of NK cells.

Ginseng

Panax ginseng augments NK cell activity and boosts cytokine production that lowers inflammation via a polysaccharide called ginsan.33

Melatonin

Melatonin, a neurohormone produced by your pineal gland, is a well-recognized modulator of cancer risk that may also boost NK production. A 2005 paper discussed the immunoregulatory action of melatonin on your innate immune system, and that exogenous melatonin (melatonin supplementation) "augments NK cells and monocytes in both the bone marrow and the spleen with a latency of 7 to 14 days."34