totbWtoTvpw

1v

bausvidv

sWtl1a

visimctq

0d

Vaccine 25 (2007) 4983–4984

Editorial

Pre- or post-pandemic influenza vaccine?

cpv

2o

2

Gaa

2

stv“

2

casvdisesnt

It is generally accepted that it is just a matter of time beforehe world will be confronted with another pandemic outbreakf influenza that will cause considerable morbidity and mor-ality worldwide. Medical supplies will be insufficient andoth social and economic disruption will take place. Theorld Health Organisation (WHO) has advocated that coun-

ries should develop pandemic preparedness plans to controlr mitigate the effects of a future influenza pandemic [1].he availability of a safe and effective pandemic influenzaaccine that can be used to vaccinate the world populationreventively, would be the most effective and cost-effectiveay to combat such a disaster.

. What are the main hurdles to develop such aaccine?

The influenza virus on which the pandemic vaccine shoulde based is not known. Obviously, the highly pathogenicvian influenza virus (HPAI) H5N1, which has spread in annprecedented large area in the past decade, should be con-idered a serious candidate. However, other avian influenzairuses, like the H7N7 and H9N2 subtypes that have recentlynfected large numbers of humans, are among the candi-ates that may be at the basis of the next pandemic influenzairus.

The current global production capacity of trivalent sea-onal influenza vaccine is about 400 million doses per year.

ith a world population of more than 6.5 billion people andhe probability that two vaccine doses should be used in aargely naı̈ve population, it should be envisaged that about3 billion doses of pandemic vaccine would be required fordequate pandemic preparedness.

The time needed from the moment that the vaccine seedirus is available until the first vaccine dose can be used,s currently 4 months at best. Almost a century ago, whenteamboats dominated world travel, the pandemic “Span-sh flu” virus spread around the world within a mere 3

onths. Consequently, the time needed to manufacture vac-ines today, coupled with the ease and accessibility of airravel (allowing the pandemic influenza virus to spread moreuickly than before), will in fact require a pandemic vac-

ooam

264-410X/$ – see front matter © 2007 Elsevier Ltd. All rights reserved.oi:10.1016/j.vaccine.2007.05.033

ine to become available after the start of the pandemiceriod, likely after the first wave, or rather, as a post-pandemicaccine.

. How may these problems be solved? There arenly three options to date

.1. “Sit back and wait”

So far, most countries have chosen to sit back and wait.iven the imminent threat, this option would be difficult to

ccept and could only be defended if other options were notvailable.

.2. “Vaccinate now”

Vaccinating now, would be the other end of the spectrum,ince we do not currently know the exact subtype or strain ofhe future pandemic influenza virus. If the actual vaccine andirus strains will not match, the protection offered with thispriming” approach may be low or even absent.

.3. “Stockpile a candidate pandemic vaccine”

Stockpiling a candidate pandemic vaccine is currentlyonsidered by the WHO [2] and seems to be the mostttractive strategy available. Data that have recently been pre-ented at scientific meetings have shown that certain influenzaaccines adjuvanted with proprietary adjuvants provide aegree of intra-subtypic cross-reactivity against drifted H5N1nfluenza virus strains and this is achieved in an antigenparing way. This has resulted in broad protection from het-rologous intra-subtypic challenge infection. Stockpiling ofuch a candidate pandemic vaccine would offer the opportu-ity to start vaccination directly at the onset of the pandemic,hus slowing its spread and reducing morbidity and mortality

f the vaccinated population. Attempts to contain the spreadf the disease by ring vaccination, as is the policy with thepplication of veterinary vaccines in the face of an outbreak,ight also form a plank of the policy at the time of a new out-

4 e 25 (2

bs

•

•

ts

•

•

wa

R

[

[

[

984 Editorial / Vaccin

reak. Crucial elements of such a pre-pandemic stockpilingtrategy are:

The viral antigens should be easily replaceable to matchnewly emerging virus strains.� In case of a drifted strain of the same subtype, the stock-

piled antigen can be used for priming, which will thenbe followed by a boost with the vaccine containing thewell-matched antigen within months.

� In case of a virus of another subtype, the antigen shouldbe replaceable within months to allow early pandemicvaccination.

It should be possible to store the adjuvant separately fromthe antigen and it should have a long shelf life. Preferably,the adjuvant should be effective in seasonal influenza vac-cines for high risk groups, allowing annual replacementfor a portion of the adjuvant stockpile, which continuouslykeeps the stockpile refreshed.

According to this strategy, the vaccination component ofhe pandemic preparedness plan recommended by WHO [1],hould contain two key elements:

Separate stockpiling of adjuvant and rapidly replaceableviral antigen.

Sufficient vaccine production capacity to produce thematched viral antigen within months. This can best beachieved by increasing today, seasonal trivalent influenzavaccine manufacturing for up to 30% of the population [3].

007) 4983–4984

Currently, with a pandemic clock ticking and not knowinghat time it is, the stockpiling of a pre-pandemic vaccine

ccording to this principle appears to be the best strategy.

eferences

1] World Health Organization. WHO Global Pandemic Preparedness Plan.Available at: http://www.who.int/entity/csr/resources/publications/influenza/GIP 2005 5Eweb.pdf.

2] World Health Organization. WHO Rapid Advice Guidelines on phar-macological management of humans infected with avian influenzaA (H5N1) virus. Available at: http://www.who.int/entity/medicines/publications/WHO PSM PAR 2006.6.pdf.

3] The European Scientific Working group on Influenza. ESWI PositionDocument. Available at: http://www.eswi.org/influenza vaccinationfor one third of the population of the european union eu 25 memberstates by 2010.cfm.

European EditorAlbert D.M.E. Osterhaus ∗

Department of Virology, Erasmus MC,Faculty Building, ’s-Gravendijkwal 230,

3015 CE Rotterdam,The Netherlands

∗

Tel.: +31 10 4088066; fax: +31 10 4089485.E-mail address: a.osterhaus@erasmusmc.nl

Available online 29 May 2007