Should You Choose The High-Dose Flu Vaccine?

Between patients last week the skeptical cardiologist skipped over to the employee health office at St. Luke’s and requested he be given a flu shot.

To my surprise, I was given a choice between a “high dose” flu shot which was “recommended for individuals 65 and older” and the regular quadrivalent flu vaccine.
I hadn’t been aware of this “high dose” flu shot previously thus had not had a chance to research it.  My time was limited and I decided to go with the high dose flu vaccine hoping that high dose did not also mean more chance for side effects.
Fortunately, I had no side effects and thus far have not contracted the flu.

Influenza More Deadly In Elderly But Vaccine Less Effective

Influenza, of course, is a huge killer which causes around 36,000 deaths per year in the United States. We adults 65 and older particularly vulnerable to complications of influenza and we are the ones that account for most of the more than 200,000 hospitalizations per year from the disease.
Hospital cardiology consultations typically spike during flu season as a bad case can worsen heart failure or trigger heart attacks and arrhythmias.
Although vaccination is the most effective intervention against influenza and associated complications, older individuals mount a lower antibody response to the vaccine compared to younger individuals.

Fluzone HD: High Dose Antigen Which Increases Antibody Reponse

To improve protect strategies to improve antibody responses to influenza vaccine in the older population, such as increasing the amount of antigen in the vaccine have been developed.
The vaccine I received is called Fluzone HD and is manufactured by the French pharmaceutical company Sanofi. It is a high-dose, trivalent, inactivated influenza vaccine (IIV3-HD) and contains four times as much hemagglutinin (HA) as is contained in standard-dose vaccines.
AFter studies demonstrating an acceptable safety profile and superior immunogenicity as compared with a standard-dose vaccine, IIV3-HD was licensed for use in the United States in December 2009,

Studies Show Improved Relative Efficacy Of Fluzone Compared to Standard Dose Flu Vaccine

A study published NEJM in 2014 proved the clinical superiority of Fluzone. It has a relative efficacy compared to standard vaccines of around 24%.
The CDC summarizes it as follows

Fluzone High-Dose (HD-IIV3) met prespecified criteria for superior efficacy against laboratory-confirmed influenza to that of SD-IIV3 in a randomized trial conducted over two seasons among 31,989 persons aged ≥65 years, and might provide better protection than SD-IIV3 for this age group . For the primary outcome (prevention of laboratory-confirmed influenza caused by any viral type or subtype and associated with protocol-defined ILI), relative efficacy of HD-IIV3 compared with SD-IIV3 was 24.2% (95% CI = 9.7–36.5%).

Subsequent studies have provided further support for the improved efficacy of Fluzone according to the CDC:

These findings are further supported by results from retrospective studies of Centers for Medicare and Medicaid Services (CMS) and Veterans Administration data, as well as a cluster-randomized trial of HD-IIV3 versus SD-IIV among older adults in nursing homes  A meta-analysis reported that HD-IIV3 provided better protection than SD-IIV3 against ILI (relative VE = 19.5%; 95% CI = 8.6–29.0%); all-cause hospitalizations (relative VE = 9.1%; 95% CI = 2.4–15.3); and hospitalizations due to influenza (relative VE = 17.8%; 95% CI = 8.1–26.5), pneumonia (relative VE = 24.3%; 95% CI = 13.9–33.4), and cardiorespiratory events (relative VE = 18.2%; 95% CI = 6.8–28.1)

Should You Choose Fluzone?

Most likely, now that I have had a chance to look in detail at the studies supporting Fluzone HD for the elderly and review the CDC recommendations, I would choose it for myself for  vaccination this year.
This is not a slam dunk decision and the CDC is actually quite wishy washy in its recommendations basically saying any formulation of vaccine is OK with them

For persons aged ≥65 years, any age-appropriate IIV formulation (standard-dose or high-dose, trivalent or quadrivalent, unadjuvanted or adjuvanted) or RIV4 are acceptable options.

As the CDC points out, we need more studies comparing these different flu vaccines to help guide decision-making.
Skeptically Yours,
Addendum. Dr. Chelsea Pearson, the prominent St. Louis internist,tells me she recommends Fluzone or Flublok to her patients 65 or older.
Flublok is a quadrivalent recombinant vaccine of standard dosage.
A head to head comparison of these two vaccines would be nice to help patients and physicians decide which to take.
Cost was not an issue in my decision but a year ago Canadian health officials felt the five-fold greater cost of flu zone HD was not warranted (see here.)
N.B. Be aware there is a quadrivalent flu vaccine from Sanofi also called fluzone.  From the FDA:
Tradename: Fluzone, Fluzone High-Dose and Fluzone Intradermal
Manufacturer: Sanofi Pasteur, Inc (for Fluzone High-Dose and Fluzone Intradermal only)

  • Fluzone is indicated for active immunization of persons 6 months of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.
  • Fluzone High-Dose is indicated for active immunization of persons 65 years of age and older against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.
  • Fluzone Intradermal indicated for active immunization for use in adults 18 through 64 years of age against influenza disease caused by influenza virus subtypes A and type B contained in the vaccine.


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14 thoughts on “Should You Choose The High-Dose Flu Vaccine?”

  1. Three weeks after receiving the high dose vaccine, my arm and shoulder are painful and my reach is limited. I’ve never had this reaction to other flu shots. I was also sick for a few days. I’m not sure I’d take it again.

  2. I had the “senior” flu vaccine last year and was told that although it provided more protection for the flu strains it protected against, it offered protection against fewer strains than the regular vaccine. Nonetheless, I opted for the “senior” version again this year.

  3. Corrected post:

    To quote you, “Influenza, of course, is a huge killer which causes around 36,000 deaths per year in the United States. We adults 65 and older particularly vulnerable to complications of influenza and we are the ones that account for most of the more than 200,000 hospitalizations per year from the disease.”

    The 36,000 is influenza and pneumonia COMBINED since they are reported together.

    From a CDC publication, since taken down but still available on the Wayback Machine. See

    “Does CDC think that influenza causes most P&I deaths? No, only a small proportion of deaths in either of these two categories are estimated to be influenza-related. CDC estimated that only 8.5% of all pneumonia and influenza deaths and only 2.1% of all respiratory and circulatory deaths were influenza-related.”

    I further commend to your reading this article from the British Medical Journal from 2005 pointing out a number of inconvenient truths about this data (which are readily confirmed from other CDC data). See:

    • Bruce,
      Thanks for your comments. The actual # of flu related deaths difficult to know with certainty. In general I think death certificates are not a good way to determine the precise statistics on causes of mortality.
      That first CDC publication is also looking at respiratory and circulatory causes but everything is an estimate.
      CDC uses two categories of underlying cause of death information listed on death certificates: pneumonia and influenza (P&I) causes and respiratory and circulatory (R&C) causes. CDC uses statistical models with records from these two categories to make estimates of influenza-associated mortality. CDC uses underlying R&C deaths (which include P&I deaths) as the primary outcome in its mortality modeling because R&C deaths provide an estimate of deaths that include secondary respiratory or cardiac complications that follow influenza. R&C causes of death are more sensitive than underlying P&I deaths and more specific than deaths from all cause

  4. This is timely for me as I saw my internist 3 hours ago. I’ve gotten the high-dose before (I’m 67); he told me he’s had reactions from “everyone” to whom he’s given the trivalent. So he gave me the quadrivalent.
    Oh, and I also got the Pneumovax-23. So far, the Pneumovax arm is the only one getting sore.

  5. I have had the high dose flu shot for several years now with no adverse effects. One year also got the Quadrivalent shot with the same result. Occasionally a sore arm for a day or so, but that used to happen with the regular shots as well.

  6. I got the high dose flu shot and the next day felt achy and it was downhill sneezing, coughing , aching …several people in my neighborhood felt sick as well.. I will never take the high dose again..

  7. That’s an interesting point I never really considered in that older individuals have a blunted antibody response to typical vaccine antigen dose. The adaptive immune system is an amazing mechanism and it makes me wonder how memory T cells or MHC (major histocompatibility complex) is effected with age. It makes sense to me that plasma cell production would decrease with age, therefore decreasing antibody production and the other players like NKC and neutrophils would also be effected by decreased leukopoieses but I wonder if the memory component of the immune system is compromised as well? Perhaps its just a numbers game though with decreased ouput of all T cell and phagocytosing cells that leads to overall less immuno surveillance?

    • christian,
      Yes, An interesting finding and I have no answer to why. Your suggestions merit consideration.
      One also wonders if taking care oneself, healthy diet, regular aerobic exercise, limiting alcohol and good sleep can forestall these age related reductions in the immune response.
      For me, I find upper respiratory infections can be mostly avoided if I limit alcohol, eat lots of fresh vegetables and berries, and get >7.5 hours of quality sleep.

  8. I usually have a slight reaction to the shot the following day. This year I got the “high dose” and I’m glad I did but I didn’t feel well at all the next morning. By the end of the day I was fine. I wonder how common that is.

    • The 2014 NEJM study indicates a higher frequency of local reactions like soreness at injection site but not systemic reactions. I feel like if you are getting 4 times as much antigen your are going to get more nonspecific reactions which are more severe.
      If other readers have gotten the flu zone HD perhaps they can register their reactions in the comment section here.
      As I mentioned I had minimal soreness at injection site (really not distinguishable from what I’ve previously felt) and had no other symptoms (which is the normal after flu vaccination for me)


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