Rev. Med. Virol. 2011; 21: 203–204.Published online in Wiley Online Library

(wileyonlinelibrary.com)DOI: 10.1002/rmv.701

E D I T O R I A L

Editorial: which infladded to the next v

Reviews in Medical Virology

Copyright © 201

uenza subtype should beaccine?

Regular readers of this column will be no strangersto the strategy of deploying vaccines containingrepresentatives of influenza haemagglutinins fromamong the 16 that exist in nature [1]. The objectivewould be to prime the human immune responseso that a future pre‐pandemic vaccine could boostthis response if needed. The likely mismatch be-tween the next pandemic strain and the primingand pre‐pandemic strains may mean that infectionwas not controlled, but severe disease and deathsmight well be. Such a strategic plan could bedeployed, starting with H5 then H7 then H9 if vac-cines with sufficiently low reactogenicity could bedeveloped. They would need to be incorporatedinto a range of contemporary seasonal vaccines sothat costs were minimised. Indeed, given that mostof the cost of a vaccine programme lies with infra-structure and delivery, the incremental cost of add-ing, say, H5 antigen to the current triple (H1,H3,B)influenza vaccine would be low. It would verylikely be cost‐effective when viewed as an insurancepolicy against the costs and disruption of the inevita-bility that future pandemics of influenza will plagueus this century. A recent commentary in Naturebuilds on this concept by reminding us not to forgetH2 [2].H2 appeared suddenly in 1957, causing approxi-

mately 66 000 deaths in the USA, only 36% ofwhich were in the under 65 age group [3]. It dis-placed H1N1 as the predominant strain and ruledthe world until 1969 when it was, in turn, displacedby H3N2. In 1957 and in 1969, the new pandemicstrains were reassortants from avians, [4] so weshould start by considering protecting ourselvesagainst H2 proteins that are extant in birds. Thegood news is that avian H2 has a low mutation rate[5]. Furthermore, the H2N2 vaccine licenced in1957 can protect mice against H2N2 strains circu-lating in animals in the 2000s [6,7]. In their com-mentary, Nabel and colleagues consider severalways of protecting the public, including resurrect-ing the previously licenced 1957 vaccine that wassafe and immunogenic [2].

1 John Wiley & Sons, Ltd.

Assuming that immunogenic vaccines withacceptable reactogenicity could be made avail-able, how might they be deployed? Until re-cently, the limited amounts of influenza vaccineavailable each season were given to those leastlikely to respond; the elderly. The public couldunderstand that vaccine was being targeted to thosemost at risk of severe disease, but it makes moresense to deploy vaccine to interrupt transmission ofvirus now thatmanufacturing capacity has increased[8,9]. Accordingly, some countries have alreadyrecommended routine immunisation of children.One could envisage including an H2 componentin a childhood schedule that would have the dis-tinct advantage of targeting those who have neverseen H2 before. The alternative of adding H2 toseasonal vaccines intended for administration tosenior citizens would likely be much less effective.One criticism of deploying vaccine in children of de-fined ages is that it produces cohortswho have/havenot been offered protection. Those unprotected accu-mulate in a population andmay congregate togetheras they pass through Shakespeare’s seven ages ofman. Thus, the introduction of measles vaccine(1968 in the UK), followed by measles plus rubellaplus mumps vaccine (1988 in the UK) supplemen-ted by a mass immunisation campaign using mea-sles plus rubella vaccine, ultimately brought allthree viruses under control, but left cohorts atrisk of acquiring mumps, in particular, whenthey congregated together in university, militarytraining establishments etc. Yet, the same factscan be used to demonstrate that we have experi-ence of dealing with such cohort effects for sys-temic viruses and so should be able to handleand predict the implications of such a policyfor influenza. The creation of particular cohortsat risk would seem preferable to watching as thebirth of susceptibles and the death of immunesprogressively populates a whole country withcitizens who are fully susceptible to H2 influ-enza. Furthermore, the worried‐about cohort ef-fect might never materialise, because it could be

204 Editorial

decades before we have to face an H2 pandemicstrain, given the unpredictable timing of thosethat have appeared since the first was recognisedin 1510 [10]. If the 2009 swine flu pandemic hastaught us anything, it should be to expect the

Copyright © 2011 John Wiley & Sons, Ltd.

unexpected while declining to be presumptuousenough to offer any predictions.

P. D. Griffiths

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ev. Med. Virol. 2011; 21: 203–204.DOI: 10.1002/rmv