April 11, 2016
3 min read

Influenza vaccine effectiveness varies by type, subtype

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A recently published meta-analysis of seasonal and monovalent influenza vaccination studies suggested substantial variation in vaccine effectiveness across influenza types and subtypes.

Vaccination was reported to provide moderate to high protection against H1N1pdm09, H1N1 (pre-2009) and type B influenzas, according to the researchers. However, greatly reduced vaccine effectiveness (VE) was observed during H3N2 influenza seasons, highlighting a need to develop alternative manufacturing methods for this particular subtype, they wrote.

Test-negative design studies yield type-specific VE data

“In a previous meta-analysis of [randomized clinical trials (RCTs)] in healthy adults, we found that pooled vaccine efficacy was 59% against all strains,” Edward A. Belongia, MD, of the Marshfield Clinic Research Foundation in Wisconsin, and colleagues wrote. “Although the RCT is the optimal design to minimize bias and confounding, it has important limitations. RCTs are often limited to one or two seasons, enroll healthy individuals, have low power to measure efficacy by subtype and are not feasible to do annually.”

To avoid these issues and report VE, Belongia and colleagues conducted a meta-analysis of published studies that used a test-negative design (TND) to report estimates by influenza type and subtype. TND studies published from Jan. 1, 2004 to March 31, 2015 that reported VE for at least one season of H3N2, H1N1, H1N1pdm09 or type B; recruited patients based on predefined illness criteria and PCR confirmation; and reported results from age-adjusted logistic regression models or age-stratified VE estimates were eligible for inclusion. The researchers excluded studies that were restricted to hospitalized or special populations, examined live-attenuated vaccine or studied pre-pandemic seasonal vaccines against H1N1pdm09. Data from these studies relevant to the analysis were extracted and examined for each included type and subtype.

Low H3N2 VE suggests need for improvements

Of the 3,368 identified publications, 56 were selected for full review and met the researchers’ eligibility criteria. These primarily were conducted within Europe and North America, and 93% were published after 2010. Of the 114 reported VE estimates, 30% were for seasonal vaccines against H3N2, 32% type B, 25% H1N1pdm09, 4% against H1N1 (pre-2009) and 9% for monovalent vaccine against H1N1pdm09.

Age-unrestricted analysis found high heterogeneity for VE against H3N2 and type B, but low heterogeneity for VE against H1N1pdm09. Pooled VE was variable between types and subtypes, ranging from 73% (95% CI, 61-81) for monovalent H1N1pdm09 and 33% for H3N2 (95% CI, 26-39). Furthermore, seasonal H1N1 (pre-2009) VE was 67% (95% CI, 29-85), seasonal H1N1pdm09 VE was 61% (95% CI, 57-65) and Type B VE was 54% (95% CI, 46-61). Analysis of H3N2 by antigenic similarity a showed variant VE 23% (95% CI, 2-40), while VE predominantly similar to the vaccine reference strain demonstrated 33% VE (95% CI, 22-43). Disparities in VE also were present when analyzing by age group.

The researchers noted some of the limitations of their analysis, such as the scarcity of eligible studies before 2009 and the growing evidence of previous seasonal vaccine’s effect on subsequent VE. However, they wrote these results demonstrate an immediate need to improve the effectiveness of poorly performing vaccines.

“We have shown that influenza vaccines provide substantial protection against H1N1pdm09, H1N1 (pre-2009) and type B, and reduced protection against H3N2,” Belongia and colleagues wrote. “An accumulating body of evidence suggests that egg-based manufacturing is not optimal for H3N2 influenza viruses that are poorly adapted for growth in eggs. A crucial need exists for alternative vaccine technologies that generate greater protection against H3N2 than do current vaccines, and product-specific VE studies will be needed to assess their effect after licensure.”

Early data shows 2015-2016 vaccine 59% successful

Preliminary data reported in a CDC press statement released in February suggested the 2015-2016 influenza vaccine was 59% effective. More specifically, it was 51% effective against the predominant H1N1 and 76% effective against all influenza.

This is a substantial improvement over the 2014-2015 vaccine, which reported 23% efficacy against circulating H3N2 due to antigenic drift.

The components of next season’s influenza vaccine already have been determined by the FDA, which adopted WHO’s recommendations in a unanimous committee vote in March. WHO recommended the trivalent influenza vaccine contain A/California/7/2009 (H1N1)pdm09-like virus, A/Hong Kong/4801/2014 (H3N2)-like virus and B/Brisbane/60/2008-like virus. It also recommended that quadrivalent vaccines should include B/Phuket/3073/2013-like virus. - by Dave Muoio


CDC. Seasonal Influenza Vaccine Effectiveness, 2005-2015. http://www.cdc.gov/flu/professionals/vaccination/effectiveness-studies.htm. Accessed April 8, 2016.

Disclosure: Belongia reports research support from MedImmune. Please see the full study for a list of all other authors’ relevant financial disclosures.