We recently published a report in Clinical Infectious Diseases summarizing 11 studies published since 2013 that describe rates of waning immunity in a single season among individuals vaccinated against seasonal influenza using the traditional inactivated vaccine. 1 These studies, though variable in their approaches, reach the important conclusion that vaccine effectiveness diminishes more rapidly than expected, particularly against influenza A/H3N2 and B subtypes. For example, in a study by Kissling et al, vaccine effectiveness for A/H3N2 declined to 0% as early as 93 days post-vaccination, while Ferdinands et al found that vaccine effectiveness for A/H3N2 declined 7% each month post-vaccination. 2,3 These studies raise the concern that early recipients of the vaccine could become vulnerable to influenza during peak months of flu activity; the findings merit a vaccine policy discussion regarding optimal timing of vaccination.


Changes in Current ACIP Guidance

The Advisory Committee on Immunization Practices (ACIP) has historically valued total vaccine coverage over the possible effects of waning immunity. 4 The 2018-19 ACIP guidance on seasonal influenza vaccine has been modified to reflect the growing body of evidence of waning immunity. 5 Though the guidance acknowledges that waning immunity may result in poor coverage later in the season, ACIP warns that delaying vaccination may result in missed opportunities and cause difficulties in vaccinating a large portion of the population in a condensed amount of time. ACIP recommends vaccination before the end of October. The American Academy of Pediatrics (AAP) guidelines for 2018-19, on the other hand, encourage vaccination as soon as it is available, with a first dose preferably by the end of October. 6


Mitigating the Effects of Waning Immunity

Over the past 10 years, several contributing factors have led to earlier influenza vaccinations, including the 2009 H1N1 pandemic, during which a nonpandemic strain containing seasonal trivalent vaccine was heavily promoted and available much earlier than the pandemic monovalent vaccine. In subsequent seasons, as public health authorities seek to meet national vaccination goals, millions of people are vaccinated by early September and, due to waning immunity, may reenter the susceptible population during peak flu activity. 

We suggest several possible changes to mitigate the effect of waning immunity, including:

  1. Optimizing the calendar by delaying vaccine to better maintain immunity during months of peak flu activity
  2. Evaluating the potential for expanded use of adjuvanted, recombinant, or high-dose vaccines to strengthen immune response and lengthen duration of immunity
  3. Evaluating the possibility of a 2-dose vaccine schedule to boost immunity (of note, a child’s first flu vaccination is a 2-dose schedule)
  4. Improving the manufacturing process to eliminate egg-adaptations and improve strain matching
  5. Prioritizing the development of a conserved-antigen “universal” vaccine


Dilemma of Overall Vaccine Coverage Vs Protection During Peak Months

The challenge posed by waning immunity is not trivial, nor easily solved. From a population perspective, the goal of a seasonal influenza campaign should be to protect as many people as possible for the duration of each season. At an individual level, informed decisions should be made in collaboration with healthcare providers. For example, earlier immunization may be more appropriate for pregnant women who are due to deliver in the fall, as their newborns will be unable to receive flu vaccine until they reach 6 months old. Young and healthy individuals may have flexibility to wait until later to be vaccinated but may interact less frequently with healthcare providers and could represent missed opportunities to vaccinate. Further complicating this issue is the unpredictability of flu activity in communities, cities, counties, and states. 

While technical solutions are evaluated and brought forth through clinical trials, we suggest that delaying vaccination at least until September, and ideally until October, is an appropriate step to minimize the effects of waning immunity. Local health departments, schools, pharmacies, occupational clinics, and other frequent providers of flu vaccine should consider the value of delayed vaccination and emphasize the benefits of continued vaccination throughout November to February. It is important for healthcare providers and individuals to be informed about the costs and benefits of early vaccination and possible implications of waning immunity and to make decisions accordingly.


References

  1. Rambhia KJ, Rambhia MT. Early bird gets the flu. What should be done about waning intraseasonal immunity against seasonal influenza? Clin Infect Dis 2018 [epub ahead of print]. 
  2. Kissling E, Valenciano M, Larrauri A, et al. Low and decreasing vaccine effectiveness against influenza A(H3) in 2011/12 among vaccination target groups in Europe: results from the I-MOVE multicentre case-control study. Euro Surveill 2013;18(5):20390. 
  3. Ferdinands JM, Fry AM, Reynolds S, et al. Intraseason waning of influenza vaccine protection: evidence from the US Influenza Vaccine Effectiveness Network, 2011-12 through 2014-15. Clin Infect Dis 2017;64(5):544-550. 
  4. Grohskopf LA, Sokolow LZ, Broder KR, et al. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2017-18 influenza season. MMWR Recomm Rep 2017;66(2):1-20. 
  5. Grohskopf LA, Sokolow LZ, Broder KR, Walter EB, Fry AM, Jernigan DB. Prevention and control of seasonal influenza with vaccines: recommendations of the Advisory Committee on Immunization Practices—United States, 2018-19 influenza season. MMWR Recomm Rep 2018;67(3):1-20.
  6. Committee on Infectious Diseases. Recommendations for prevention and control of influenza in children, 2018-2019. Pediatrics 2018 [epub ahead of print].