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Published Date: 2012-08-10 12:45:18
Subject: PRO/AH> Influenza (68): A(H3N2)v, age-related seroprotection
Archive Number: 20120810.1238403

INFLUENZA (68): A(H3N2)V, ACE-RELATED SEROPROTECTION
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Date: Thu 9 Aug 2012
From: Danuta Skowronski <Danuta.Skowronski@bccdc.ca> [edited]

Re: Influenza A/(H3N2)v: age-related seroprotection
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In response to recent ProMED-mail postings [see listing below] of additional H3N2v detections in the United States (US) in July and August 2012, we would like to provide reference to a paper now appearing in the Journal of Infectious Diseases (JID) entitled "Cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v" [1], selected as "Editor's Choice", permitting Open Access to the manuscript at http://jid.oxfordjournals.org/content/early/2012/08/07/infdis.jis500.abstract.

This paper reports age-specific seroprotection at greater precision, and across a broader age span, than previously available from earlier, smaller serosurveys [2-4]. In addition, the paper presents age-related antibody findings for ancestral and contemporary human influenza strains for context and comparison, and also reports vaccine-induced cross-reactive responses to H3N2v in children, young and older adults, including following receipt of adjuvanted formulation for the elderly.

The main results and conclusions include:
1. In Canada, where H3N2v has not yet been detected, the population is not entirely immunologically naive to this novel strain, with 25 percent of more than 1000 sera collected in the fall 2010 (approximately 100 sera per decade across the lifespan) showing hemagglutination inhibition (HI) antibody titre 1:40 or more, considered by convention as the seroprotective threshold.

2. There is considerable variation in H3N2v seroprotection by age: none in [children] less than 5 years and less than 20 percent up to 14 years or over 40 years of age had HI [hemagglutination inhibition] antibody titre 1:40 or more. Conversely, half of teens and adults between 14 and 40 years of age showed H3N2v seroprotection. H3N2v antibody titres and the proportion seroprotected were greatest in adults 20-29 years of age.

3. Comparison with age-specific seroprotection for ancestral and contemporary human influenza virus strains suggests a cohort effect explaining age-related patterns of cross-reactive antibody to H3N2v, likely predicated on robust priming to related viruses of childhood. Possible reasons for decline in cross-reactive H3N2v antibody in middle-age adults are proposed.

4. Varying threshold titres and subset assessment by microneutralisation assay showed similar age-related patterns.

5. Recent seasonal trivalent inactivated influenza vaccine (2010-11 or 2011-12) does not meaningfully improve H3N2v seroprotection (less than 15 percent of immunized children, young adults, or elderly seroconverted to H3N2v). An MF59-adjuvanted formulation cannot be relied upon to stimulate greater cross-reactive antibody responses against H3N2v in the elderly.

References
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1. Skowronski DM, Janjua NZ, De Serres G, et al: Cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v. J Infect Dis Published online 7 Aug 2012. doi:10.1093/infdis/jis500. Advance access available at http://jid.oxfordjournals.org/content/early/2012/08/07/infdis.jis500.abstract.
2. Skowronski DM, De Serres G, Janjua NZ, et al: Cross-reactive antibody to swine influenza A(H3N2) subtype virus in children and adults before and after immunization with 2010/11 trivalent inactivated influenza vaccine in Canada, August to November 2010. Euro Surveill 2012; 17(4): pii=20066. Available at http://www.eurosurveillance.org/ViewArticle.aspx?Articleid=20066.
3. Centers for Disease Control and Prevention (CDC). Antibodies cross-reactive to influenza A (H3N2) variant virus and impact of 2010-11 seasonal influenza vaccine on cross-reactive antibodies -- United States. MMWR Morb Mortal Wkly Rep 2012; 61: 237-41. Available at http://www.cdc.gov/mmwr/PDF/wk/mm6114.pdf.
4. Waalen K, Kilander A, Dudman S, et al: Age-dependent prevalence of antibodies cross-reactive to the influenza A(H3N2) variant virus in sera collected in Norway in 2011. Euro Surveill 2012; 17(19). Pii:20170. Available at http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20170.

Other details of interest can be found in the manuscript. We thought it worthwhile to draw this paper to the attention of ProMED-mail readership given ongoing H3N2v clusters in the US and to inform of risk assessment activities.

--
Danuta M Skowronski MD, FRCPC, on behalf of co-authors
Communicable Disease Prevention and Control Services
BC Centre for Disease Control
Vancouver,
British Columbia,
Canada
<Danuta.Skowronski@bccdc.ca>

[ProMED-mail welcomes this opportunity to draw the attention of readers to these valuable and opportune studies on cross-reactive and vaccine-induced antibody to emerging swine influenza A(H3N2)v. Cases of a novel swine-origin influenza A(H3N2) variant (A(H3N2)v) have recently been identified in the US, primarily among children (detailed in the ProMED-mail posts listed below).

Danuta Skowronski and colleagues have determined cross-reactive antibody to A(H3N2)v by age and assess whether seasonal trivalent inactivated influenza vaccine, with/without adjuvant, may improve seroprotection. They have established that a substantial proportion of adolescents and young adults have cross-reactive antibody against A(H3N2)v, whereas children and older adults show broad susceptibility. Furthermore recent formulations of seasonal trivalent inactivated influenza vaccine, with/without adjuvant, do not substantially improve seroprotection. They conclude that a specific vaccine would be needed in the event A(H3N2)v establishes epidemic spread. - Mod.CP]

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