Author(s): Rita Czako aff1 , Kanta Subbarao [*] aff1
antigenic mismatch; avian influenza; pandemic influenza; prepandemic vaccine; prime boost
Influenza viruses are enveloped viruses belonging to the Orthomyxoviridae family. Influenza viruses are grouped into three types: A, B and C. Of these, influenza A and B viruses are responsible for epidemic human disease. Influenza A viruses are further divided into subtypes distinguished by antigenic properties of the viral surface proteins: hemagglutinin (HA) and neuraminidase (NA). These proteins are critical for entry into host cells and for release of mature, infectious progeny virus and are the main targets of the human immune response [1 ]. To date, 16 subtypes of HA and nine subtypes of NA have been isolated from waterfowl and shorebirds, the natural hosts of influenza A viruses [ 2 ]. In addition, sequences of two novel influenza-like viruses have been identified in bats and classified as two novel subtypes: H17N10 and H18N11 [ 3,4 ]. A segmented RNA genome, error-prone RNA polymerase and the ability to infect many different species contribute to the substantial diversity of influenza A viruses in nature.
Two influenza A subtypes, H1N1 and H3N2, currently co-circulate with influenza B viruses in humans. Vaccination is the most effective strategy for prevention and control of influenza and its associated morbidity and mortality [5 ]. Strain selection, manufacture and deployment of seasonal influenza vaccines for the control of these viruses have become a routine component of national health programs in many countries. Antigenic drift in the HA protein necessitates annual reformulation of seasonal vaccines to maximize vaccine efficacy. Prediction of the influenza variants that will dominate a given influenza season is a challenging task that is based on global surveillance of circulating influenza viruses [6 ]. The lead time of this 'reactive' approach to control of seasonal influenza is several months. Between 1999 and 2009, four seasonal vaccine formulations selected for implementation in the northern hemisphere failed to adequately match the epidemic strain because a new antigenic variant emerged after the vaccine strain composition decision was made [7 ]. Mismatch events have occurred at a similar frequency in the southern hemisphere in recent years [8 ].
The assessment of the pandemic potential of animal influenza viruses is a complex task. There have been four pandemics of influenza in the last century. In addition, interpandemic periods have been punctuated by occasional epidemics caused by viruses with unusual properties, for example, enhanced pathogenicity or transmission in certain subgroups of the population [9 ]. Furthermore, several avian influenza viruses (AIV) have caused sporadic zoonotic infections in humans [10 ]. Although human-to-human transmission of these zoonotic viruses has not been efficient, their potential to acquire this property renders them a pandemic threat.
The public health response to the 2009 H1N1 pandemic (H1N1pdm) was rapid and included the development and deployment of monovalent H1N1pdm vaccines. However, production and distribution were not rapid enough to prevent the second wave of the pandemic [11 ]. Effective control of pandemic influenza may therefore require a different philosophical approach...