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Influenza History and Vaccine: Mind the Gap Series

Core IM

In part 1 of our flu series, we explore the history and present day understanding of the flu, just in time for flu season!

First, listen to the podcast. After listening, ACP members can take the CME/MOC quiz for free.


Up to 0.5 AMA PRA Category 1 Credits ™ and MOC Points
Expires December 18, 2022   active


Free to Members


Podcasts and Audio Content


Core IM

Welcome to Core IM, a virtual medical community! Core IM strives to empower its colleagues of all levels and backgrounds with clinically applicable information as well as inspire curiosity and critical thinking. Core IM promotes its mission through podcasts and other multimodal dialogues. ACP has teamed up with Core IM to offer continuing medical education, available exclusively to ACP members by completing the CME/MOC quiz.

  1. The infamous flu pandemic of 1918 sadly led to at least 25 million deaths and triggered research into influenza and the creation of a vaccine.
    1. What we now know of as “the flu” was first thought to a bacterial infection due to Haemophilus influenzae, which is where the virus got its name.
  2. Influenza has at least 3 species that infect humans (A, B, and C), but only A and B have been known to cause significant disease.
    1. Flu A is the most prevalent worldwide (on average around 75% of cases) and possibly more virulent, although new data challenges this.
    2. Flu B has caused localized epidemics in parts of Africa and South America.
  3. Influenza naming conventions require the flu species, followed by where it was isolated, the strain number, and the year for example: Influenza A/California/04/2009.
    1. Influenza A is further separated into various serotypes differentiated by how antibodies respond to their hemagglutinin and neuraminidase proteins.
    2. For example, the “Swine Flu” pandemic of 2009 was due to Influenza A/California/04/2009 (H1N1), hence the nickname “H1N1.”
  4. The flu vaccine specifically targets the hemagglutinin protein, whereas anti-virals used to treat the flu target the neuraminidase protein.
    1. Hemagglutinin is an envelope protein that allows the virus to enter cells
    2. Neuroaminidase is an envelope protein that allows the virus to leave cells after replicating in them.
  5. The vaccine formulation changes every year to match the virus’s latest mutations, caused by antigenic drift and antigenic shift.
    1. The strains are recommended by the WHO and a US group called the VRBPAC based on trends they see from epidemiology and genetic data.
  6. There are 3 ways to produce the inactivated flu vaccine:  the age-old chicken egg culture, the newer mammalian cell culture, or the recombinant method (which uses insect cells).
    1. But, the first flu vaccines were created using ferrets! They have a uniquely strong immunogenicity against viral antigens and are still used to test vaccine effectiveness today.
    2. Today, most vaccines are made using the chicken egg method, although new methods are gaining in popularity.
    3. Of note, the CDC recently changed its guidelines to specify that patients with an egg allergy can get any vaccine. While patients who had a hive reaction to eggs previously required monitoring for >30 mins after getting the vaccine, the new guidelines now reserve this caution for patients with anaphylaxis allergy only.
  7. There is also an activated (but attenuated, i.e. not very strong) flu vaccine that is delivered nasally. As with other live vaccines, it should not be used in pregnant or immunocompromised patients.
  8. The flu vaccine can be trivalent or quadrivalent, meaning it contains 3 or 4 strains.
    1. Typically it includes a flu A strain similar to the 2009 H1N1 strain, a flu A strain of the H3N2 variant (related to the 1918 strain!), and 1-2 flu B strains.
    2. Data suggests the quadrivalent vaccine may be slightly more effective; it is also now the most commonly available vaccine type in the US. However the FDA still states that both vaccines are effective enough, so recommend getting whichever type is available.
  9. Vaccine effectiveness must be measured retrospectively and is typically around 40%.
    1. Effectiveness captures real world performance, compared to efficacy, which measures lab performance in ideal conditions.
    2. With herd immunity, the risk of getting the flu decreases even if not everyone has gotten the vaccine.
  10. Current frontiers in flu research include:
    1. Figuring out what to do with waning immunity (e.g. vaccine response) in the elderly. Do they need the high dose vaccine?
    2. Developing a flu vaccine that is universal and may not need to be given every year.


Janine Knudsen, MD - Host, Editor, CME questions

Steven Liu, MD - Host, Editor


Denise McColloch, MD

Aditya Shah, MD

Those named above unless otherwise indicated have no relationships with any entity producing, marketing, reselling, or distributing health care goods or services consumed by, or used on, patients.

Release Date: December 18, 2019

Expiration Date: December 18, 2022

CME Credit

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the American College of Physicians and the Core IM.  The American College of Physicians is accredited by the ACCME to provide continuing medical education for physicians.

The American College of Physicians designates each enduring material (podcast) for 0.5 AMA PRA Category 1 Credit™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

ABIM Maintenance of Certification (MOC) Points

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 1 medical knowledge MOC Point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program.  Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

How to Claim CME Credit and MOC Points

After listening to the podcast, complete a brief multiple-choice question quiz.  To claim CME credit and MOC points you must achieve a minimum passing score of 66%.  You may take the quiz multiple times to achieve a passing score.