Types of Flu Vaccines: Which Quadrivalent Flu Vaccine is the Best Flu Shot for You?

Each season clinics must answer questions regarding influenza, including inquiries about the different types of the flu vaccines, and which one is best.

MyFluVaccine is also here to help answer questions related to the flu vaccine, as well as track the spread of the flu for the US for the current flu season.

What are the different types of flu vaccines available?

There are two main types of flu vaccines available to help combat the seasonal flu: inactivated influenza vaccines and live attenuated influenza vaccines. When properly administered, both help to protect from the flu, but cannot cause the flu.

It is recommended that all people 6 months and older receive a flu vaccine, with some rare exceptions. Discuss the options with your healthcare provider to see which vaccine is best for you and available in your area.

Inactivated Influenza Vaccines

Inactivated influenza vaccines (IIV) can be used for those 6 months and older and are injected. The term "inactivated" means the vaccine/injection will not cause influenza (though minor symptoms may occur as the body works to build antibodies against influenza) and that the virus has been "killed" and purified. Children who have not been vaccinated for the flu should receive two doses, four weeks apart.

Live Attenuated Influenza Vaccines

Live attenuated flu vaccines (LAIV) are for people 2-49 years old with no chronic medical conditions. A LAIV comes in the form of a nasal spray and is administered as such. This type is made from live but weakened (attenuated) viruses, which may cause short-term, mild flu-like symptoms after the intranasal vaccine is administered, but the nasal spray does not cause influenza.

For those who fear injections or needles, this may be a good option, but it is important to confirm with your healthcare provider.

How many different flu vaccines are there?

In the US, there are nine types of flu vaccines available. The Centers for Disease Control and Prevention (CDC) have created a table to show the influenza vaccines for the 2022-23 flu season1, and the links below provide information about the individual influenza vaccines used in the US.

What are the different types of flu vaccine administration?

The Flu Shot:

Flu shots are typically administered by needle and are usually injected in the patient's upper arm.

Advantages: This is the most widely available type of flu vaccine, and depending on the brand/type, the flu shot can be administered to all age groups.

Disadvantages: For those with a severe fear of needles or injections, this may seem like a scary option. However, the injection is quick and side effects are often quite mild.

Nasal Spray Flu Vaccine:

Typically, a live attenuated influenza vaccine (LAIV) is administered as a nasal spray.

Advantages: The nasal spray serves a wide range of ages, for those aged 2-49, and if a patient has a fear of needles or injections, the nasal spray is a more approachable option.

Disadvantages: Babies under two cannot receive the nasal spray flu vaccine, nor can those over age 49, so this is not an appropriate option for infants and the elderly.

High-Dose Flu Vaccine:

Licensed for people 65 years and older, this high-dose vaccine contains 4 times the amount of antigen as a regular flu shot.

Advantages: This high dosage helps the body to build more immunity to flu viruses.

Disadvantages: This is only approved for use in seniors 65+.

Jet Injector:

While the name may sound more to do with flight, a jet injector is actually a medical product that uses a high-pressure stream of fluid that injects the vaccine without the use of a needle. This medical technology was developed in the 1960s. The only available flu vaccine available by jet injection is Afluria® Quadrivalent.

Advantages: Afluria® Quadrivalent via jet injector is approved for a wide range of adults, people aged 18 through 64.

Disadvantages: A jet injector is not approved for use in children nor the elderly. However, Afluria® Quadrivalent can be administered for people 6 months and older via needle and syringe.

Adjuvanted Vaccine:

Similar to the high-dose flu vaccine, the adjuvanted flu vaccine is licensed for people 65 and older and designed to create a stronger immune response by adding an extra ingredient—an adjuvant—to the vaccine. Adjuvants are added to vaccine formulations to enhance efficacy. In the case of Fluad® Quadrivalent, MF59® is made from an emulsion of squalene oil (a substance which occurs in humans, animals, and plants, and is purified for vaccine manufacturing) that enhances the immune process. MF59® has been administered in flu vaccines to millions of people since 1997 (in Europe) and in the US since 2016. Adjuvants help in the manufacturing process as well because the amount of virus needed is reduced, which allows for greater production and, therefore, greater availability.

Cell-Based Flu Vaccines:

Different than flu vaccines grown using eggs, cell-based flu vaccines are not grown in eggs but are grown in cells of mammalian origin. No animals are harmed in this process, and cell-based vaccines are not reliant on egg supply, which has the potential to speed up manufacturing. In addition, cell-based flu vaccines have been recorded as providing better protection2 (for those 65 and older) and better chances of virus "matching" with circulating flu strains.

The CDC describes the cell-based flu manufacturing process3 as such: "First, CDC or one of its laboratory partners, uses influenza viruses that have been grown in cultured mammalian cells to make CVVs [Candidate Vaccine Viruses], which are then provided to a vaccine manufacturer.

Next, the vaccine manufacturer inoculates the CVVs into cultured mammalian cells (instead of into chicken eggs) and allows the CVVs to replicate (i.e., make copies) for a few days. Then, the virus-containing fluid is collected from the cells and the virus antigen is purified. The manufacturing process continues with purification, virus inactivation, and testing. Finally, FDA tests and approves the vaccines prior to release and shipment."

Flucelvax® Quadrivalent is the only cell-based flu vaccine in the US.

Recombinant Flu Vaccines:

In contrast to the cell-based flu vaccines, recombinant flu vaccines are grown through a method that is egg-free. This is a great option for patients who are worried about egg allergy reactions.

Recombinant flu vaccines are made synthetically using the chosen flu virus' genetic makeup, which allows for creation of the antigen which will fuel the protective immune response in the vaccine recipient. There is only one FDA-approved recombinant influenza vaccine in the US, and the manufacturing process of recombinant vaccines is the fastest because this process can skip the CVV portion.

What is the difference between the quadrivalent and trivalent flu vaccine?

The difference between quadrivalent and trivalent flu vaccines is the number of virus strains included in the creation of the vaccine: four for quadrivalent flu vaccines and three for trivalent flu vaccines. Both types of vaccines have similar, mild side effects and are continually examined for safety and effectiveness.

A quadrivalent influenza vaccine4 is designed to protect against four forms of flu: usually two Influenza A strains, and two Influenza B strains. Flu vaccines in the United States are all quadrivalent to provide wider protection against the spread of potential influenza strains. In other parts of the world, trivalent flu vaccines, which protect against three forms of influenza are also offered.

How many different quadrivalent flu vaccines are there?

For the 2023-2024 flu season, there are nine quadrivalent flu vaccines available.

  1. Afluria® Quadrivalent
  2. Fluad® Quadrivalent
  3. Fluarix® Quadrivalent
  4. Flublok® Quadrivalent Recombinant
  5. Flucelvax® Quadrivalent
  6. Flulaval® Quadrivalent
  7. FluMist® Quadrivalent
  8. Fluzone® High-Dose Quadrivalent
  9. Fluzone® Quadrivalent

How many different trivalent flu vaccines are there?

For the 2022-2023 season, there are no trivalent flu vaccines available in the US. Quadrivalent flu vaccines are preferred because they include an additional strain for more protection.

Are there different brands of the flu shot?

There are several brands and manufacturers of the flu vaccine. For flu vaccines available in the US for this flu season, the manufacturers include AstraZeneca, GlaxoSmithKline, Sanofi, and Seqirus.

It is projected that the US will be supplied with 173.5 – 183.5 million doses of influenza vaccines for the 2022-2023 season, yet, based on flu progression and activity of the season, these numbers are subject to change.

What type of vaccination is the flu vaccine?

The Influenza A and B viruses that often circulate have RNA gene segments5. Flu vaccines are not mRNA vaccines like some of the COVID-19 vaccines, but mRNA influenza vaccines are currently being researched.

What is the difference between the regular flu shot and the senior flu shot?

For those younger than 65, the CDC does not recommend a particular flu vaccine over another, but for those over 65, three types of flu vaccines are advised: Fluad® Quadrivalent, Flublok® Quadrivalent Recombinant, or Fluzone® High-Dose Quadrivalent. These types of vaccines have been found to offer more protection and be more effective for people over 65 years. However, if for some reason the above recommended vaccines for those 65+ are not available in your area, any age-appropriate flu vaccine is advised.

In comparing Flublok® Quadrivalent Recombinant vs Fluad® Quadrivalent vs Fluzone® High-Dose Quadrivalent, it is important to consider health conditions and any allergies or sensitivities (specifically, eggs). If you have an allergy or aversion to egg-based products, then Flublok® Quadrivalent Recombinant may be your best bet, and it is approved for use in those 18+, including seniors 65 and over.

For egg-based vaccines approved for those 65+, you have the option of Fluad® Quadrivalent vs Fluzone® High-Dose Quadrivalent. Fluad® Quadrivalent—manufactured by Sequris—contains four influenza strains and is a standard-dose flu vaccine. Fluad® also contains an adjuvant (MF59), which aids in immune response.

According to prescribing information from Sanofi, "Fluzone High-Dose has '4x the amount of antigen per strain of Fluzone vaccine' and is 'proven in a head-to-head randomized controlled trial to prevent more cases of influenza in adults 65+ compared with Fluzone [Quadrivalent] vaccine.'"

Is Flucelvax® Quadrivalent a live virus?

Flucelvax® Quadrivalent is an inactivated and cell-based flu vaccine, which means it is not grown in eggs, and the virus strains have been inactivated or purified. The virus strains used are not "live" and will not cause influenza.

Which influenza vaccine is best?

All vaccines used in the US are closely monitored by the CDC and FDA for safety and effectiveness, and flu vaccines are created for different purposes and populations. With that in mind, a vaccine that is best for one person might not be best for someone else. It is important to check with your healthcare provider to determine which influenza vaccine is best for you based on age, allergies, health status and/or conditions, etc.

But, recently, the Advisory Committee on Immunization Practices (ACIP) did make a recommendation for the use of specific flu vaccines for the 65+ population. These include Fluad® Quadrivalent, Flublok® Quadrivalent Recombinant, and Fluzone® High-Dose Quadrivalent. Because the elderly often carries the burden of flu and severe flu-related illnesses, this population is heavily encouraged to get one of the preferred flu vaccines created for those 65+. However, if the vaccines formulated for those 65 and older are not available in a particular area, a similar flu vaccine is recommended.

Are all flu vaccines the same?

In the US, all influenza vaccines are quadrivalent, which means they have been formed to protect against four different flu viruses (usually two Influenza A viruses, and two Influenza B viruses) depending on the season. To find out more about the specific influenza strain combinations for the 2022-2023 flu season, see Influenza Vaccine for the 2022-2023 Season | FDA6.

Types of Flu Vaccines Include:

  1. Standard-dose flu shot (virus is grown in eggs)*: Approved for use in children 6 months+ and anyone 18+. These types of flu shots are administered in the arm muscle by needle. Afluria® Quadrivalent, Fluarix® Quadrivalent, Flulaval® Quadrivalent, and Fluzone® Quadrivalent.
  2. Adjuvanted flu shot (egg-based)*: This vaccine is for use in people who are 65+ and contains an adjuvant (a substance used to enhance the body's immune response to an antigen). Fluad® Quadrivalent.
  3. High-dose flu shot (egg-based)*: Designed and approved for those 65+, this has four times the antigen amount than standard-dose flu vaccines. Fluzone® High-Dose Quadrivalent.
  4. Live attenuated nasal spray flu vaccine (egg-based)*: This flu vaccine spray is created with weakened live flu viruses and is administered through the nose. While it is approved for people ages 2 – 49, it is not recommended for use in pregnant people, those who are immunocompromised, or those with some medical conditions.* FluMist® Quadrivalent For a list of certain conditions, see the CDC's shared information, The Nasal Spray Flu Vaccine (CDC)7.
  5. Cell-based flu shot: A completely egg-free vaccine, this type is grown via cell culture and is approved for those 6 months and older. Flucelvax® Quadrivalent.
  6. Recombinant flu shot: Another egg-free option, this flu shot is approved for people 18 years+. This type of flu shot is made with three times the antigen than other flu vaccine options, which aids your body in creating a deeper immune response. An antigen is part of a vaccine that builds antibodies, thus creating greater protection in the body. Flublok® Quadrivalent Recombinant.

Check with your healthcare provider to know which vaccine is right for your age and medical condition(s).

*It is recommended that individuals who are severely allergic to eggs be vaccinated for the flu in a healthcare setting with medical professionals who can notice and treat severe allergic reactions. However, based on numerous studies, it is unlikely that severe allergic reactions will occur with the use of egg-based flu vaccines. As noted above, there are two completely egg-free flu vaccine options: Flublok® Quadrivalent Recombinant and Flucelvax® Quadrivalent.

Footnotes:

  1. TABLE. Influenza vaccines — United States, 2022–23 influenza season* | CDC
  2. Relative Effectiveness of Influenza Vaccines Among the United States Elderly, 2018-2019 | NIH
  3. How Influenza (Flu) Vaccines Are Made | CDC
  4. Quadrivalent Influenza Vaccine | CDC
  5. Influenza Virus Genome Sequencing and Genetic Characterization | CDC
  6. Influenza Vaccine for the 2022-2023 Season | FDA
  7. Live Attenuated Influenza Vaccine [LAIV] (The Nasal Spray Flu Vaccine) | CDC

References:

  1. Adjuvants and Vaccines | Vaccine Safety | CDC
  2. CDC Director Adopts Preference for Specific Flu Vaccines for Seniors | CDC
  3. Immunology and efficacy of MF59-adjuvanted vaccines | NIH
  4. Influenza Vaccine Production and Design | NIH: National Institute of Allergy and Infectious Diseases
  5. Quadrivalent Influenza Vaccine | CDC
  6. Seasonal Flu Vaccines | CDC
  7. Traditional and New Influenza Vaccines | PMC
  8. Types of Flu Shots: Trivalent, Quadrivalent, Side Effects, and More | Healthline
  9. Types of seasonal influenza vaccine | WHO