Thursday, October 26, 2017

Eurosurveillance: Low H3N2 Vaccine Effectiveness In Australia's 2017 Flu Season


The news regarding the effectiveness of the H3 component of last year's flu vaccine (which is carried over to this fall's Northern Hemisphere vaccine) continues to disappoint, with an interim analysis published today in Eurosurveillance on the VE (vaccine effectiveness) experienced during Australia's most recent (and very rough) flu season.

This isn't exactly an unexpected finding, as over the past few months we've seen a number of reports on this topic, including:
As we discussed earlier this summer in The Enigmatic, Problematic H3N2 Influenza Virus, the Vaccine Effectiveness (VE) of the H3N2 component has lagged in recent years compared to H1N1 and influenza B, believed at least partially due to increased diversity among circulating H3 strains and to mutations that can crop up during the (primarily egg-based) manufacturing process.
As a result, last winter we saw just a modest level of protection (34%) against H3N2, according to the CDC's MMWR report of June 30th (see 2016–17 Influenza Vaccine Effectiveness).
According to today's interim VE report from Australia - while this year's flu vaccine performed reasonably well against H1N1 (50%) and the Influenza B (57%) - it's VE against seasonal H3N2 averaged only 10%.

Rapid communication Open Access

Low interim influenza vaccine effectiveness, Australia, 1 May to 24 September 2017 

 Sheena G Sullivan1,2,3, Monique B Chilver3, Kylie S Carville4, Yi-Mo Deng1, Kristina A Grant4, Geoff Higgins5, Naomi Komadina1, Vivian KY Leung1, Cara A Minney-Smith6, Don Teng7, Thomas Tran4, Nigel Stocks3, James E Fielding2,4 

The ongoing Australian 2017 influenza season was so far characterised by record-high laboratory-confirmed influenza notifications [1], high consultation rates, high hospitalisation and mortality rates, particularly in New South Wales [2], large numbers of institutional outbreaks [2] and media attention. The southern hemisphere influenza vaccine used in Australia for this season was a quadrivalent formulation comprised of an A/Michigan/45/2015 (H1N1)pdm09-like virus, an A/Hong Kong/4801/2014 (H3N2)-like virus, a B/Brisbane/60/2008-like virus (of the B/Victoria/2/87 lineage) and a B/Phuket/3073/2013-like virus (of the B/Yamagata/16/88 lineage) [3,4]. This same vaccine composition is being used in the upcoming northern hemisphere for the 2017/18 influenza season [5]. Here we report interim influenza vaccine effectiveness estimates for 2017 in Australia, using sentinel surveillance data. 

Vaccine effectiveness (VE) was estimated following a case–control test-negative design, where VE is estimated from the odds ratio (OR) comparing the odds of vaccination among test-positive and test-negative patients. The limitations of this design have been discussed at length [10,11]. Estimates were adjusted for week of specimen collection (cubic spline with 4 knots), and age group (spline with knots at 5, 15, 35, 65, 75 years).

VE estimates are shown in Table 2. Overall VE was 33% (95%CI: 17 to 46). This estimate appeared to be skewed by the very low estimate for A(H3), which was 10% (95%CI: -16 to 31), whereas estimates were higher for A(H1)pdm09 (VE: 50%; 95%CI: 8 to 74) and B (VE: 57%; 95%CI: 41 to 69). VE for A(H3) 3C.2a viruses was 5% (95%CI: -51 to 40), while the estimate for 3C.2a1 was 19% (95%CI: -42 to 55). For patients vaccinated in the 2016 season, VE for A(H3) was 3–4% regardless of whether they were also vaccinated in 2017. In contrast, the highest VE point estimates for influenza B were observed among those vaccinated in both 2016 and 2017.


 Our interim analysis suggests moderate VE against influenza A(H1)pdm09 and influenza B. However, VE was low against influenza A(H3). The antigenic data reflect ongoing issues with A(H3) candidate vaccine viruses which, when propagated in eggs, rapidly acquire adaptive changes in the haemagglutinin which alter antigenicity. Cell-based vaccines, which are less affected by this, are only licensed in the United States, were not available in Australia in 2017 and will also not be available for the upcoming European season. The significant genetic diversity of circulating viruses, many of which exhibit amino acid substitutions in key antigenic and glycosylation sites, also makes it difficult to select candidate vaccine viruses with high coverage.

This was the second season for which the A/Hong Kong/4801/2015-containing vaccine was used in Australia [3,12], and campaigns currently underway in the northern hemisphere are also using it for a second time [5,13]. During the 2016/17 northern hemisphere season interim VE estimates ranged from 15% (95%CI: –11 to 35) to 43% (95%CI: 29 to 54) [14-17]. 

It is unclear whether sequential vaccination will result in lower estimates for 2017/18, but our VE estimates were particularly low for people who received vaccine in 2016 and for older adults, 76% of whom were sequentially vaccinated.
This finding is consistent with a modelling study which predicts low VE for sequentially vaccinated persons when the vaccine composition is identical, but the antigenic distance between the vaccine and circulating strains is high [18]. However, confounding due to prior infection status and negative interference from pre-2016 vaccines could not be controlled for in our analysis, and may have introduced bias.

In contrast to A(H3), VE estimates for influenza B were moderate and the combined effects of vaccination in 2016 and 2017 did not blunt effectiveness for influenza B, even though the composition remained the same. Similarly, VE for the few A(H1)pdm09 cases recruited was moderate, although low for Australia at 50% (95%CI: 8 to 74), where VEs have ranged from 54% to 79% in the past [6,7]. This was the one component of the 2017 vaccine that was updated since 2016, from A/California/7/2009 to A/Michigan/45/2015.

This study provides interim estimates of the 2017 southern hemisphere influenza vaccine in the outpatient setting and may not apply to inpatient settings or severe illness. Interim estimates can reliably predict final season estimates [19], particularly when made after the peak [20], as is the case here.
Should the circulating A(H3) influenza viruses predominate in the 2017/18 northern hemisphere influenza season [21], our results suggest that the vaccine may confer limited protection. Health authorities should consider other influenza prevention measures, including antivirals and health promotion messaging, in the event of a severe season and low VE against A(H3).
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Despite a disappointingly low VE against H3N2, the flu vaccine will likely provide many recipients with at least some degree of protection - and if an unusually severe H3N2 season materializes this winter - you'll probably be glad for any advantage you can get.
In addition, Influenza B - which often follows in the spring - can take a heavy toll, and the VE against that flu strain is pretty decent.
All of which still makes getting the flu shot – along with practicing good flu hygiene (washing hands, covering coughs, & staying home if sick) – important steps you can take to help reduce the risk of getting the flu this winter.

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