Effectiveness Of Pandemic Influenza Vaccines Research Articles

An Advax-CpG55.2 adjuvanted recombinant hemagglutinin vaccine provides immunity against H7N9 influenza in adult and neonatal mice

There is a major unmet need for strategies to improve the immunogenicity and effectiveness of pandemic influenza vaccines, particularly in poor responder populations such as neonates. Recombinant protein approaches to pandemic influenza offer advantages over more traditional inactivated virus approaches, as they are free of problems such as egg adaptation or need for high level biosecurity containment for manufacture. However, a weakness of recombinant proteins is their low immunogenicity. We asked whether the use of an inulin polysaccharide adjuvant (Advax) alone or combined with a TLR9 agonist (CpG55.2) would enhance the immunogenicity and protection of a recombinant hemagglutinin vaccine against H7N9 influenza (rH7HA), including in neonatal mice. Advax adjuvant induced predominantly IgG1 responses against H7HA, whereas Advax-CpG55.2 adjuvant also induced IgG2a, IgG2b and IgG3 responses, consistent with the TLR9 agonist component inducing a Th1 bias. Advax-CpG55.2 adjuvanted rH7HA induced high serum neutralizing antibody titers in adult mice. In newborns it similarly overcame immune hypo-responsiveness and enhanced serum anti-rH7HA IgG levels in 7-day-old BALB/C and C57BL/6 mice. Immunized adult mice were protected against a lethal H7N9 virus challenge. When formulated with Advax-CpG55.2 adjuvant, greater protection was seen with rH7HA than with inactivated H7 whole virus antigen. Advax-CpG55.2 adjuvanted rH7HA represents a promising influenza vaccine platform for further development.

I-MOVE: a European network to measure the effectiveness of influenza vaccines

Since 2007, the European Centre for Disease Prevention and Control (ECDC) has supported I-MOVE (influenza monitoring vaccine effectiveness), a network to monitor seasonal and pandemic influenza vaccine effectiveness (IVE) in the European Union (EU) and European Economic Area (EEA). To set up I-MOVE, we conducted a literature review and a survey on methods used in the EU/EEA to measure IVE and held expert consultations to guide the development of generic protocols to estimate IVE in the EU/EEA. On the basis of these protocols, from the 2008/09 season, I-MOVE teams have conducted multicentre case–control, cohort and screening method studies, undertaken within existing sentinel influenza surveillance systems. The estimates obtained include effectiveness against medically attended laboratory-confirmed influenza and are adjusted for the main confounding factors described in the literature. I-MOVE studies are methodologically sound and feasible: the availability of various study designs, settings and outcomes provides complementary evidence, facilitating the interpretation of the results. The IVE estimates have been useful in helping to guide influenza vaccine policy at national and European level. I-MOVE is a unique platform for exchanging views on methods to estimate IVE. The scientific knowledge and experience in practical, managerial and logistic issues can be adapted to monitor surveillance of the effectiveness of other vaccines.

Using surveillance data to estimate pandemic vaccine effectiveness against laboratory confirmed influenza A(H1N1)2009 infection: two case-control studies, Spain, season 2009-2010

BackgroundPhysicians of the Spanish Influenza Sentinel Surveillance System report and systematically swab patients attended to their practices for influenza-like illness (ILI). Within the surveillance system, some Spanish regions also participated in an observational study aiming at estimating influenza vaccine effectiveness (cycEVA study). During the season 2009-2010, we estimated pandemic influenza vaccine effectiveness using both the influenza surveillance data and the cycEVA study.MethodsWe conducted two case-control studies using the test-negative design, between weeks 48/2009 and 8/2010 of the pandemic season. The surveillance-based study included all swabbed patients in the sentinel surveillance system. The cycEVA study included swabbed patients from seven Spanish regions. Cases were laboratory-confirmed pandemic influenza A(H1N1)2009. Controls were ILI patients testing negative for any type of influenza. Variables collected in both studies included demographic data, vaccination status, laboratory results, chronic conditions, and pregnancy. Additionally, cycEVA questionnaire collected data on previous influenza vaccination, smoking, functional status, hospitalisations, visits to the general practitioners, and obesity. We used logistic regression to calculate adjusted odds ratios (OR), computing pandemic influenza vaccine effectiveness as (1-OR)*100.ResultsWe included 331 cases and 995 controls in the surveillance-based study and 85 cases and 351 controls in the cycEVA study. We detected nine (2.7%) and two (2.4%) vaccine failures in the surveillance-based and cycEVA studies, respectively. Adjusting for variables collected in surveillance database and swabbing month, pandemic influenza vaccine effectiveness was 62% (95% confidence interval (CI): -5; 87). The cycEVA vaccine effectiveness was 64% (95%CI: -225; 96) when adjusting for common variables with the surveillance system and 75% (95%CI: -293; 98) adjusting for all variables collected.ConclusionPoint estimates of the pandemic influenza vaccine effectiveness suggested a protective effect of the pandemic vaccine against laboratory-confirmed influenza A(H1N1)2009 in the season 2009-2010. Both studies were limited by the low vaccine coverage and the late start of the vaccination campaign. Routine influenza surveillance provides reliable estimates and could be used for influenza vaccine effectiveness studies in future seasons taken into account the surveillance system limitations.

“I-MOVE” towards monitoring seasonal and pandemic influenza vaccine effectiveness: lessons learnt from a pilot multi-centric case-control study in Europe, 2008-9

Within I-MOVE (European programme to monitor seasonal and pandemic influenza vaccine effectiveness (IVE)) five countries conducted IVE pilot case-control studies in 2008-9. One hundred and sixty sentinel general practitioners (GP) swabbed all elderly consulting for influenza-like illness (ILI). Influenza confirmed cases were compared to influenza negative controls. We conducted a pooled analysis to obtain a summary IVE in the age group of >or=65 years. We measured IVE in each study and assessed heterogeneity between studies qualitatively and using the I2 index. We used a one-stage pooled model with study as a fixed effect. We adjusted estimates for age-group, sex, chronic diseases, smoking, functional status, previous influenza vaccinations and previous hospitalisations. The pooled analysis included 138 cases and 189 test-negative controls. There was no statistical heterogeneity (I2=0) between studies but ILI case definition, previous hospitalisations and functional status were slightly different. The adjusted IVE was 59.1% (95% CI: 15.3-80.3%). IVE was 65.4% (95% CI: 15.6-85.8%) in the 65-74, 59.6% (95% CI: -72.6 -90.6%) in the age group of >or=75 and 56.4% (95% CI: -0.2-81.3%) for A(H3). Pooled analysis is feasible among European studies. The variables definitions need further standardisation. Larger sample sizes are needed to achieve greater precision for subgroup analysis. For 2009-10, I-MOVE will extend the study to obtain early IVE estimates in groups targeted for pandemic H1N1 influenza vaccination.

A cell‐based H7N1 split influenza virion vaccine confers protection in mouse and ferret challenge models

In recent years, several avian influenza subtypes (H5, H7 and H9) have transmitted directly from birds to man, posing a pandemic threat. We have investigated the immunogenicity and protective efficacy of a cell based candidate pandemic influenza H7 vaccine in pre-clinical animal models. Mice and ferrets were immunised with two doses of the split virus vaccine (12-24 microg haemagglutinin) with or without aluminium hydroxide adjuvant and challenged 3 weeks after second dose with the highly pathogenic A/chicken/Italy/13474/99 (H7N1) virus. The H7N1-specific serum antibody response was also measured. After challenge, viral shedding, weight loss, disease signs and death (only mice) were recorded. Low-to-modest serum antibody titres were detected after vaccination. Nevertheless, the vaccine induced significant protection from disease after challenge with the wild-type virus. In the murine lethal challenge model, vaccination effectively prevented death and, furthermore, formulation with adjuvant reduced excessive weight loss and viral shedding. In ferrets, vaccination reduced viral shedding and protected against systemic spread of the virus. We have extended to the H7 subtype the finding that protective efficacy may not be directly correlated with the pre-challenge levels of serum antibodies, a finding which could be of great importance in assessing the potential effectiveness of pandemic influenza vaccines.