JID: Stockpiled A/H7N9 Vaccines Induce Robust Non-Neutralizing Functional Antibodies Against Drifted H7N9

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In order to accelerate the manufacturing of a pandemic vaccine, the WHO, CDC, and other researchers analyze novel viruses as they emerge, and over the years have selected dozens to become candidate vaccine viruses (CVV) (see CDC: Making a Candidate Vaccine Virus For HPAI Avian Flu).

Over the past two decades more than 36 H5 CVVs have been selected by WHO for development, along with 14 H7N9 CVVs.

Because these viruses continually evolve, stockpiling large quantities of vaccine - which have a relatively short shelf life as it is - quickly becomes impractical. But small runs, of thousands - up to a few million doses - have been made for several particularly worrying strains.

When an older clade of the virus is supplanted by a newer one - such as we saw with the sudden emergence of an HPAI H7N9 virus in China two years ago - a new vaccine is almost always required.  

But today we've a study that suggests that older versions of a vaccine might not be entirely useless in the opening days of a pandemic. While they may not prevent infection, there is hope they may reduce the severity of infection.

Given that an emerging pandemic strain might very likely differ antigenically from any vaccine we already have stockpiled, being able to use our current (very limited) stocks to blunt the impact of the first wave would be very useful.

Particularly in front-line workers, like HCWs, who will be at greatest risk.

But there is a big caveat attached.  All of this is predicated on in vitro studies (described below) using sera from previously vaccinated individuals, the results of other relevant mouse studies, and our less-than-complete understanding of the human immune system. 

While the authors make a good case, how effective it would be in actual practice  is less than certain. The authors acknowledge this uncertainty in the Discussion section of their paper, where they write:

In light of these new findings, it is conceivable that the cross-reactive ADCC-mediating antibodies induced by MF59 and/or AS03 adjuvanted A(H7N9) vaccines based on a 2013 A(H7N9) virus may contribute to the recovery of severe A(H7N9) infections from recent 5th wave A(H7N9) viruses, even in the presence of only low levels of cross-reactive neutralizing antibodies.

Follow the link to read the full manuscript, after which I'll have a brief postscript:

Stockpiled avian influenza A(H7N9) vaccines induce robust, non-neutralizing functional antibodies against antigenically drifted 5th wave A(H7N9) viruses

Weimin Zhong Min Z Levine
The Journal of Infectious Diseases, jiz295, https://doi.org/10.1093/infdis/jiz295

Published: 05 June 2019

PDF
 
Abstract

Human infections caused by avian influenza A(H7N9) viruses have raised concerns of a pandemic. The capability of the current stockpiled A(H7N9) vaccines to induce cross-protective, non-neutralizing functional antibodies against antigenically drifted A(H7N9) viruses has not been evaluated before.

Here we show that vaccination with either MF59- or AS03-adjuvanted inactivated A(H7N9) vaccines elicited robust, cross-reactive ADCC-mediating and neuraminidase-inhibiting functional antibodies against the antigenically drifted A(H7N9) viruses that emerged recently during the 5th wave outbreak in China, including a highly pathogenic A(H7N9) human isolate.

Such cross-reactive humoral immunity may provide vital first-line defense against fatal outcomes in case of a A(H7N9) pandemic.

        (Continue . . . )


The notion that a mismatched vaccine might produce some degree of lessening of a flu infection's severity isn't new, at least with seasonal flu vaccines.

• In May of 2018, in CID Journal: Flu Vaccine Reduces Severe Outcomes in Hospitalized Patients, we saw a study that suggested that among those hospitalized with influenza, having been vaccinated is associated with less severe illness, lower mortality, and shorter hospitalization stays.
• And a study published 18 months ago (see CMAJ Research: Repeated Flu Vaccinations Reduce Severity of Illness In Elderly), found that repeated yearly flu vaccinations reduce the severity of illness in the elderly - usually the hardest hit segment of the population - even when it fails to prevent infection.

Whether getting the seasonal flu shot every year would provide some measure of enhanced survivability during a pandemic is far less certain, but it is a dividend I would gladly take.

The receipt of a more closely matched pre-pandemic vaccine, however, might just provide us with a badly needed edge in the opening weeks and months of a pandemic.