Why Lengthen mRNA Vaccine Dosing Interval? CDC Staff Explain

Extended dosing intervals for Pfizer or Moderna vaccines may be considered for certain individuals ages 12 to 64 years, not only to lower the risk of vaccine-associated myocarditis, but to potentially improve vaccine effectiveness, CDC staff said on Thursday.

According to the agency’s new interim guidance, young people ages 12 to 39 may especially benefit from a second mRNA dose 8 weeks after their first dose.

However, the regular 3-week interval for Pfizer and 4-week interval for Moderna is appropriate for patients who are moderately to severely immunocompromised, adults ages 65 and up, those who need rapid protection (such as “during high levels of community transmission”), and children ages 5 to 11.

In a call with clinicians, CDC staff reviewed the evidence to support these changes, first discussed at the CDC’s Advisory Committee on Immunization Practices (ACIP) meeting earlier this month. Sara Oliver, MD, of the CDC, reviewed the mainly international data that led to the decision by showing lower rates of vaccine-associated myocarditis in men ages 18 to 24 with a dosing interval of 8 weeks or more.

Moreover, data from England showed that vaccine effectiveness for Pfizer was higher against symptomatic infection with an extended interval of more than 6 weeks versus a standard interval of 3 to 4 weeks across age groups.

“An extended interval may promote efficient T cell expansion and long-term memory cell persistence,” Oliver said.

When clinicians on the call asked why the 8-week interval, as opposed to a longer one, Oliver noted that it was due to a “tradeoff” between benefits and risks.

“The benefits of extending the intervals appear to level off at about 8 weeks, whereas the additional benefits were minimal” after that, she said, adding that it was almost too long a time to be protected with only one mRNA vaccine dose “especially during a pandemic.”

While Oliver noted that vaccine-associated myocarditis risks were highest for younger men, she added that “females can also experience myocarditis” and could potentially benefit from an extended dosing interval if they did not fall into a group that needed rapid protection.

Additional changes to CDC’s interim clinical guidelines included an update to guidance for moderate to severely immunocompromised individuals ages 12 and up, recommending that they receive a booster dose (fourth dose) of mRNA vaccine at least 3 months after their three-dose primary series. A three-dose primary series is also recommended for moderate to severely immunocompromised children ages 5 to 11.

Moderate to severely immunocompromised adults receiving the Johnson & Johnson vaccine should receive a second dose of mRNA vaccine at least 28 days later and a booster dose 2 months after that, for a total of three doses.

CDC staff also added that clinicians caring for immunocompromised patients may use their clinical judgment on a case-by-case basis to administer mRNA COVID vaccines outside of FDA and CDC dosing intervals “when the benefits of a different vaccination schedule or dosage” outweigh the risks.

Clinicians also asked CDC staff about the rumblings surrounding a fourth dose of vaccine for healthcare workers.

While Oliver said they didn’t have any recommendations for additional doses just yet, CDC staff would be working with their vaccine effectiveness team and the FDA; and “if it appears that we need additional doses either in a specific population or the population at large,” they will evaluate the safety and effectiveness data, and discuss it at a future ACIP meeting.

However, Oliver said that she didn’t anticipate “any updated recommendation in the imminent future.”