Perspective

Suboptimal vaccine effectiveness against influenza A/H3N2 identified

Researchers from the British Columbia Centre for Disease Control observed suboptimal vaccine effectiveness against the influenza A/H3N2 virus during the 2010-2011 winter season and also detected genetic variants to the virus using a sentinel surveillance platform.

During this time frame, there were many outbreaks related to influenza A/H3N2 at long-term care facilities in Canada. The outbreaks also affected vaccinated staff. Interim data from the sentinel surveillance system, which incorporated genotypic, phenotypic and epidemiologic indicators, identified genetic variants and suboptimal vaccine effectiveness.

“Unlike other vaccines, the influenza vaccine must be reformulated and re-administered each year to keep pace with ongoing changes in circulating virus strains,” Danuta Skowronski, MD, epidemiology lead of Influenza & Emerging Respiratory Pathogens at BC Centre for Disease Control, told Infectious Disease News. “For this reason, real-time monitoring of circulating strains, their relatedness to chosen vaccine components and their impact on vaccine protection are important. To do this requires the efficient harnessing of molecular, individual and population-level information.”

Danuta Skowronski

Danuta Skowronski

The researchers analyzed nasal/nasopharyngeal swabs and epidemiologic data from 1,718 participants who presented with influenza-like illness. Among these participants, 93 tested positive with A(H1N1)pdm09, 408 had A/H3N2 and 199 had influenza B. Patients who tested negative for influenza were considered controls. Among the cases, 16% received the influenza vaccine and among the controls, 24% received the vaccine.

The vaccine efficacy for adults aged 20 to 49 years was 65% for A(H1N1)pdm09 and 66% for influenza B. For A/H3N2, however, the vaccine efficacy was only 39%.

Two hundred thirty-three specimens were isolated for hemagglutination inhibition characterization. This process showed that all of the A(H1N1)pdm09 isolates were A/California/7/2009-like and all of the A/H3N2 isolates were A/Perth/16/2009-like, demonstrating that all of the isolates were well matched to the vaccine. However, on phylogenetic analysis, only two of the A/H3N2 isolates belonged to the A/Perth/16/2009 vaccine clade. Most belonged to the A/HongKong/2121/2010 variant, and the remainder belonged to the A/Victoria/208/2009 variant, both of which were not matched to the vaccine.

“Understanding influenza virus evolution and its impact on vaccine effectiveness real time can help inform adjunct prevention and treatment measures when suboptimal vaccine protection is identified,” Skowronski said. “Having a systematic platform to collect influenza viruses and accurately assess their impact on vaccine effectiveness is important in selecting new strains to be included in revised formulations each year.”

References:

Skowronski DM. Clin Infect Dis. 2012;55:332-342.

Disclosures:

The researchers report financial relationships with Becton Dickinson, Gen-Probe, GlaxoSmithKline, Hoffmann-LaRoche, Merck, Pfizer, Roche, Sanofi-Pasteur and Siemens.

Researchers from the British Columbia Centre for Disease Control observed suboptimal vaccine effectiveness against the influenza A/H3N2 virus during the 2010-2011 winter season and also detected genetic variants to the virus using a sentinel surveillance platform.

During this time frame, there were many outbreaks related to influenza A/H3N2 at long-term care facilities in Canada. The outbreaks also affected vaccinated staff. Interim data from the sentinel surveillance system, which incorporated genotypic, phenotypic and epidemiologic indicators, identified genetic variants and suboptimal vaccine effectiveness.

“Unlike other vaccines, the influenza vaccine must be reformulated and re-administered each year to keep pace with ongoing changes in circulating virus strains,” Danuta Skowronski, MD, epidemiology lead of Influenza & Emerging Respiratory Pathogens at BC Centre for Disease Control, told Infectious Disease News. “For this reason, real-time monitoring of circulating strains, their relatedness to chosen vaccine components and their impact on vaccine protection are important. To do this requires the efficient harnessing of molecular, individual and population-level information.”

Danuta Skowronski

Danuta Skowronski

The researchers analyzed nasal/nasopharyngeal swabs and epidemiologic data from 1,718 participants who presented with influenza-like illness. Among these participants, 93 tested positive with A(H1N1)pdm09, 408 had A/H3N2 and 199 had influenza B. Patients who tested negative for influenza were considered controls. Among the cases, 16% received the influenza vaccine and among the controls, 24% received the vaccine.

The vaccine efficacy for adults aged 20 to 49 years was 65% for A(H1N1)pdm09 and 66% for influenza B. For A/H3N2, however, the vaccine efficacy was only 39%.

Two hundred thirty-three specimens were isolated for hemagglutination inhibition characterization. This process showed that all of the A(H1N1)pdm09 isolates were A/California/7/2009-like and all of the A/H3N2 isolates were A/Perth/16/2009-like, demonstrating that all of the isolates were well matched to the vaccine. However, on phylogenetic analysis, only two of the A/H3N2 isolates belonged to the A/Perth/16/2009 vaccine clade. Most belonged to the A/HongKong/2121/2010 variant, and the remainder belonged to the A/Victoria/208/2009 variant, both of which were not matched to the vaccine.

“Understanding influenza virus evolution and its impact on vaccine effectiveness real time can help inform adjunct prevention and treatment measures when suboptimal vaccine protection is identified,” Skowronski said. “Having a systematic platform to collect influenza viruses and accurately assess their impact on vaccine effectiveness is important in selecting new strains to be included in revised formulations each year.”

References:

Skowronski DM. Clin Infect Dis. 2012;55:332-342.

Disclosures:

The researchers report financial relationships with Becton Dickinson, Gen-Probe, GlaxoSmithKline, Hoffmann-LaRoche, Merck, Pfizer, Roche, Sanofi-Pasteur and Siemens.

    Perspective
    Theodore Eickhoff

    Theodore Eickhoff

    Skowronski and co-workers have reported an interesting project in influenza surveillance; this was carried out over a one-year period during 2010-2011 over a broad area of Canada. It does represent influenza reported from a number of large viral surveillance areas, but certainly does not represent real public health reporting.

    As suggested by the title of the paper, these authors established an influenza vaccine effectiveness program in about six major medical centers following an agreed-upon protocol requiring influenza immunization or not, and the subsequent workup of all persons with symptoms who presented within 7 days of onset. With a wide range of laboratory assets available, it was possible to put together careful analyses of vaccine behavior as well as a close look at viral variant behaviors.

    The investigators have clearly demonstrated the enhanced power of this kind of comprehensive surveillance. They could clearly assess enhanced surveillance, increased or decreased vaccine efficacy, new variant circulation, and the like. What they have not clearly determined is whether it has all been worth it. Perhaps, however, it is still too early in this kind of field epidemiologic research to make such a determination. Personally, I would encourage rather than discourage further work in this complex field epidemiology area. Do, for example, H1N1 viruses relate at all to H3N2 viruses during a single season? If so, how? Certainly we need to see, as this report partially does, that they both occur, but do they occur together or apart? Does one have any influence on the other? And that’s before we even get to influenza B.

    Many of these answers could be obtained, I would think, with smaller scale surveys carried out simply in one or perhaps at most two medical centers. It is not clear to me what the added benefit has been of using coast-to-coast medical centers.

    • Theodore Eickhoff, MD
    • Infectious Disease News Editorial Board member