LAUSR

Influenza vaccine is the primary intervention to reduce mortality and morbidity in an influenza pandemic, in particular a severe pandemic. However, the current state of vaccine technology does not allow a rapid surge in pandemic vaccine production in the advent of a pandemic, to which the response will rely on the same production platform as seasonal vaccines. Thus how efficient a pandemic vaccine response would be depends largely on the extent of how well seasonal vaccine response to annual epidemics is rightly seized. Recognizing the shared pathways of vaccine response to both seasonal epidemics and pandemics, in 2002 WHO developed a ‘‘Global Agenda on Influenza Surveillance and Control” with an objective to increase influenza vaccine usage during inter-pandemic periods towards strengthen national and international pandemic preparedness. In 2003, the World Health Assembly (WHA 56.19) resolved to urge Member States to increase vaccination coverage of risk population [1]. In 2006, the Global Action Plan (GAP) on Influenza Vaccines was launched to promote evidence-based seasonal vaccine use, increase vaccine production capacity and stimulate research and development [2]. With the past decade’s efforts of WHO and its partners, the accumulated knowledge, understanding, experience and practice of influenza vaccines results in a renewed landscape of progress and challenges. Among others, vaccine research and development led by US Biomedical Advanced Research and Development Authority (BARDA) and increased potential vaccine production capacity pioneered by the WHO GAP have resulted in a far better pandemic preparedness [3,4]. On the other hand, the need for thorough preparedness as learnt from the recent Ebola outbreak response [5] mirrors that for an influenza pandemic, including pandemic vaccine response. The most opportunistic estimate of current monovalent pandemic vaccine production capacity of 415 million doses per year in GAP-supported Lowand Lowermiddle-income countries (GAP survey 2015 – unpublished) is far from the need to immunize the world’s population of more than 7 billion people, let alone that pandemic influenza waves may have swept over globally within a year. Aside from the supply, the current 50–60% effectiveness of seasonal vaccines, even with perfect match of vaccine viruses with circulating viruses [6], is rather disappointing and calls for better protective vaccines. The perception on influenza vaccines is further affected when there is a mismatch between vaccine composition and circulating viruses, which can result in effectiveness much lower than 50%. The scientific complexities e.g. issues associated with egg-propagated and cell-propagated virus isolates, and newly emerged viral features of seasonal H3N2 viruses [7,8] which is not fully comprehended by growing interest of the population, press the challenge further. The relatively mild severity of the 2009 H1N1 pandemic [9] does not in any way exempt the world from a catastrophic hit at any time by the next pandemic strain of an hitherto unknown virus subtype. The threat of the next influenza pandemic is getting more vivid than ever with the spreading of avian influenza viruses [10], and increasing virus activity across the animal human ecosystem interface [11,12], of which, tip of the iceberg can be seen from the frequent as yet sporadic and extremely alarming human infections with H5, H7N9 and H9N2 avian viruses. WHO revised its pandemic preparedness plan and published an interim guidance document of Pandemic Influenza Risk Management Framework in 2013 [13], and is currently working with partners towards finalizing the pending chapter on pandemic vaccines. The complexities of vaccine response at the beginning of a pandemic were examined through an informal WHO consultation in June 2015 through scenarios, when seasonal influenza viruses may still be causing severe epidemics in parts of the world. Subsequently countries may have different priority needs for seasonal and pandemic vaccines, while a vaccine manufacturer can produce at one time either seasonal or pandemic vaccines but not both. The WHO process continued in July 2016 (unpublished) to develop response with critical elements including principles of consideration and a transparent process for decision to commence the pandemic vaccine production which might require ‘‘switch” from seasonal vaccine production. Such decision making process will not be fully operational until critical details e.g. data needs as evidence base are identified and vaccine production bottleneck solutions are in place. Except for some conditional regulatory processes [14–16] specific to pandemic vaccines, all steps of pandemic vaccine production are aligned with those of seasonal influenza vaccines. This forms the base of the pandemic vaccine preparedness strategy. Early detection of a pandemic virus and development of a highgrowth reassortant that can be used for large scale production are critical steps of pandemic vaccine response. The constraints of these early critical steps are reflected in seasonal vaccine response – which became very evident when an antigenic variant emerged