Flu Shot Timing: What's Optimal?

Maureen Salamon

August 27, 2021

Amid fresh national recommendations for COVID booster shots to ramp up waning immunity, new research examining the durability of flu vaccination indicates significantly dwindling protection just months after inoculation.  

Maximum influenza vaccine efficacy in adults occurred shortly after vaccination, followed by an average decline of 8% to 9% each month and an even swifter drop among older adults.

Even a 1- or 2-month delay in annual flu vaccination could improve vaccine effectiveness by 10% to 20%, according to the study, published August 15 in Clinical Infectious Diseases.

Dr Jill Ferdinands

Analyzing vaccine timing relative to influenza-associated hospitalizations among more than 5500 adults, the findings are broadly consistent with both early and more recent studies, said study author Jill Ferdinands, PhD, an epidemiologist in the Influenza Division of the National Center for Immunization and Respiratory Diseases at the US Centers for Disease Control and Prevention (CDC).

"These findings are not surprising," Ferdinands told Medscape Medical News. "In the very first successful trial of inactivated influenza vaccine in 1943, the study's authors observed that antibodies to influenza declined by about one third within 4 to 5 months after vaccination."

US guidelines call for annual flu shots for everyone 6 months and older, but determining the best time to get vaccinated can be complicated, Ferdinands noted. Current recommendations — which Ferdinands said clinicians should continue to follow — suggest that ideally, vaccination should occur by the end of October.

But, "a better understanding of waning immunity, like the information gained by this study, could help further optimize the recommendation," she said.

Participants in the study were enrolled in the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN), presented with new or worsening cough or sputum production over the prior 10 days during the 2015-16 through 2018-19 flu seasons, and were hospitalized for acute respiratory illness.

Patients testing positive for influenza were considered cases, while those testing negative were used as controls. Participants were considered vaccinated if they had documented evidence of at least one dose of influenza vaccine at least 14 days before they became ill.

Datasets included 3016 adults (average age 60) analyzed for vaccine efficacy against hospitalizations associated with influenza A (H3N2); 1492 patients for influenza A (H1N1); and 1060 patients for influenza B/Yamagata.

Overall, 34% had obtained vaccination by the end of September, 77% by the end of October, 92% by the end of November, and 97% by the end of December.

Results were adjusted for factors such as age, race, season, past year hospitalizations, and indicators of underlying health conditions. Vaccine efficacy against influenza-associated hospitalizations declined by an average of 7.5%–8.5% for each 30 days postvaccination, depending on influenza type.

These findings were more pronounced among older adults, with those 65 and older experiencing an average decline of 10.8% in vaccine efficacy for each 30 days after inoculation.

Results suggest that delaying vaccination timing by even 1 or 2 months might improve vaccine effectiveness by 10% to 20%, Ferdinands said, and this approach deserves consideration "if [it] doesn't encroach on the annual influenza season, delay vaccine delivery, or reduce vaccine uptake."

Public health benefits could be significant, given the millions who become ill and tens of thousands who die from influenza in the US each year, she added.  

While the study didn't examine variation in waning vaccine effectiveness by vaccine type or prior vaccination history, "it was large enough to look at the decline in vaccine protection among people 65 and older, a group for whom growing evidence suggests may be more likely to experience faster declines in vaccine protection," Ferdinands noted.

A New York-based infectious disease specialist said the new study reinforces the need for a better flu vaccine "that's more effective for a longer period of time, rather than just a few months."

"It's time to see whether a two-dose flu vaccine makes sense, maybe spaced out 3 or 4 months apart," said Harish Moorjani, MD, from Phelps Hospital of Northwell Health in Tarrytown, New York.

Dr Harish Moorjani

"I think we've known in general that vaccinations, for the most part, aren't forever," Moorjani told Medscape Medical News. "In some cases they are, but that's rare. With COVID, we do know we need three doses…with influenza, we need to ask the same question: Do we need two doses?"

Moorjani praised the new research, saying it confirmed that current influenza vaccines are likely to decline in efficacy over time and that "people who are most vulnerable, including the [elderly] and those without immune competence" may experience faster drops.

He said the COVID pandemic might prove to "actually be a shot in the arm for influenza vaccine research."

"It will give us more incentive to learn more about how we make better vaccinations for influenza, because now we realize the effects of a virus can be devastating," Moorjani added. "Whatever makes this possible, we should absolutely do it."

Ferdinands reports receiving nonfinancial travel support from the Institute for Influenza Epidemiology, funded in part by Sanofi Pasteur. Moorjani has disclosed no relevant financial relationships. The study was funded by the CDC, the National Institutes of Health Clinical and Translational Science Award program, and the National Center for Advancing Translational Sciences at Vanderbilt University Medical Center.

Clinical Infectious Diseases (CID). Published online August 15, 2021. Full text

Maureen Salamon is a New Jersey-based freelance writer who has written for The New York Times, The Atlantic, CNN.com and other major outlets.

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