Fluzone High-dose vs. Standard Quadrivalent Flu Vaccine - Which To Get

Alexis Bryan27 Sep 2021

Both the high-dose and standard flu vaccines are designed to protect against four different flu viruses. Individuals between 6 months old and 64 should typically get the standard quadrivalent flu vaccine, while the Fluzone High-Dose Quadrivalent vaccine is licensed and recommended for anyone over the age of 65. The high-dose vaccine contains four times the antigen as the standard dose to elicit a stronger immune response. 

With most health insurance plans, you can get a free flu shot at your doctor’s office, several pharmacies, or an urgent care center. If you don’t have insurance, Mira can help you access affordable health coverage for preventative care, urgent care, prescriptions, lab tests, and more. 

2021-2022 Flu Vaccines and Which to Get

All vaccines in the United States is administered during the  2021-2022 flu season are quadrivalent, providing protection against two influenzas A viruses and two influenza B viruses. This means the vaccine contains 4 strains of flu to offer broad protection against the strains of flu most likely to spread during the 2021-2022 flu season. Within 2 weeks of vaccination, your body will create antibodies to protect against these strains of the flu. 

Fluzone High-dose Quadrivalent Flu Vaccine for Adults 65+

The Fluzone High-dose Quadrivalent flu vaccine is an “enhanced” vaccine specifically formulated for people 65 and older. There is also the adjuvanted flu vaccine,  FLUAD quadrivalent, which has an added ingredient to help promote a better immune response. The CDC and its Advisory Committee on Immunization Practices (ACIP) have not indicated a preference for one enhanced vaccine over the other.

People 65 years and older are administered an enhanced vaccine because they are at increased risk of serious complications from flu. Shoshana Fishbein, MPH, a director at Families Fighting Flu, explains, “Older individuals are at higher risk of getting sick from the flu because they typically have a weaker immune response to the flu vaccine. The high-dose flu vaccine was designed to offer them stronger protection against the flu virus.”

Evidence Behind the High-Dose Flu Vaccine 

A study published in The Lancet Infectious Diseases Journal found the high-dose vaccine to be 22 percent more effective than the standard dose vaccine for flu prevention among people 65 and older. Additionally, the study showed a significant reduction in flu-related hospital admissions among those who were administered the high-dose vaccine.

Fishbein adds, “High-dose vaccines are recommended for people 65 and older because their immune systems are weaker and they are more likely to die from flu. High-dose vaccines contain more flu proteins called antigens. This means that there are more of the vaccine ingredients in order for the body to create a stronger antibody response. A higher dose is necessary for people 65 and older because they comprise the majority of flu hospitalizations.”

The Centers for Disease Control’s (CDC) 2021-2022 Flu Vaccine Recommendations

Annual flu vaccination is recommended for everyone six months and older. Different flu shots are approved for people of different ages. In general, if you are pregnant or have an underlying health condition, you should still get a flu shot, but you can talk to your healthcare provider first if you are concerned. 

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The regular quadrivalent flu vaccine and high dose flu vaccine can be made using several different methods. Below we explain the three ways that flu vaccines are made: 

  1. Egg Based: Most flu shots are made with egg-based technology. The virus is grown in eggs and incubated for several days before the fluid containing the virus is extracted. The viruses are then killed (inactivated) and purified before being distributed. Even though these vaccines contain a small amount of egg protein, they are safe for people with severe egg allergies.
    There are egg-based vaccines that also include adjuvants, which are additional ingredients that help promote a better immune response.
  2. Cell culture-based: This type of inactivated flu vaccine is made from viruses grown in animal cells instead of eggs. There is currently only one inactivated cell-based flu vaccine that is approved by the FDA. There is some evidence that this type of vaccine may provide stronger protection against the flu than standard egg-based vaccines.
  3. Recombinant Flu Vaccine: The recombinant vaccine production method does not require chicken eggs or use the flu virus and is instead created synthetically. There is also only one recombinant flu vaccine that is FDA approved.

Below is a table of the available flu vaccines, the way they are made, and the age range appropriate for each type of vaccination.

Influenza Vaccines and Age Indications

Vaccine Name

Age Range

Vaccine Type 

Afluria Quadrivalent


  • ≥6 mos
Standard dose, egg based

Fluarix Quadrivalent


  • ≥6 mos
Standard dose, egg based

FluLaval Quadrivalent


  • ≥6 mos
Standard dose, egg based

Fluzone Quadrivalent

(Sanofi Pasteur)

  • ≥6 mos
Standard dose, egg based



  • ≥65 yrs
Standard dose, egg based

FluMist Quadrivalent


  • 2 through 49 yrs
Standard dose, egg based

Fluad Quadrivalent


  • ≥65 yrs
Standard dose, egg based with MF59 adjuvant

Fluzone High-Dose Quadrivalent

(Sanofi Pasteur)

  • ≥65 yrs
High dose, egg based

Flucelvax Quadrivalent


  • ≥4 yrs
Standard dose, cell culture based 

Flublok Quadrivalent

(Sanofi Pasteur)

  • ≥18 yrs

High Dose Flu Vaccine Frequently Asked Questions (FAQs)

There are several flu vaccines on the market each season, and each differs from the other slightly. The questions below aim to answer a few common questions to help you choose the best vaccine for you and be an informed healthcare consumer.

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What is the difference between High-Dose and Standard-Dose Quadrivalent flu vaccines?

The high-dose flu vaccine has four times the amount of flu virus antigen and was created for people ages 65 and older. The purpose of an “enhanced” vaccine is to help elicit a strong immune response even among people who have weaker immune systems. The standard-dose vaccines are effective for everyone under 65 years old.

This year, both the high-dose and standard-dose vaccines are quadrivalent, meaning they offer broader protection against four different flu viruses. Two of the viruses are influenza A viruses and two are influenza B viruses.

Below we outline the main differences between the standard and high dose influenza vaccines. 

Standard Quadrivalent Flu Shot vs Fluzone High-Dose


Standard Dose

High Dose

  • 2 influenza A viruses and  2 influenza B viruses
  • 2 influenza A viruses and 2 influenza B viruses
  • Contains four times the amount of antigen to create a stronger immune response
Age Range
  • 6 months and above
  • Age 65 and above
Side Effects
  • Soreness, redness, or swelling at site of injection
  • Fever (low grade)
  • Aches
  • Soreness, redness, or swelling at site of injection
  • Fever (low grade)
  • Aches
  • Headache

Is the high-dose flu vaccine more effective?

Among persons 65 years of age or older, high-dose vaccines have been shown to induce significantly higher antibody responses, thus providing better protection against flu illness. The amount of protection provided by a flu vaccine varies by flu virus type and vaccine, but generally, the high-dose flu shots are more effective than standard-dose vaccines for older adults. The effectiveness of the flu vaccines also varies each season.

Can the flu vaccine make you sick?

While the flu vaccine can give some people mild side effects, it cannot give you the flu. Any side effects are caused by your body’s immune response to the vaccination. 

The vaccines are made with inactivated (killed) viruses and can not get you sick. The most common side effect after vaccination is soreness, redness, tenderness, or swelling where the shot was given. Although uncommon, it is possible to have a low-grade fever, headache, and muscleaches 1-2 days after getting vaccinated. 

Bottom Line

There are many flu vaccines to choose from, but the most important thing is for all people six months and older to get a flu vaccine this year. As the COVID-19 Delta variant continues to spread worldwide, we need to avoid spreading the flu as well.

As flu season approaches, it is a good time to check in with your doctor or to get routine lab work done to ensure optimal health. A membership with Mira can help you access affordable health services if you are currently without health insurance.