Mass vaccination for the 2009 H1N1 pandemic: approaches, challenges, and recommendations

The 2009 H1N1 pandemic stimulated a nationwide response that included a mass vaccination effort coordinated at the federal, state, and local levels. This article examines a sampling of state and local efforts during the pandemic in order to better prepare for future public health emergencies involving mass distribution, dispensing, and administration of medical countermeasures. In this analysis, the authors interviewed national, state, and local leaders to gain a better understanding of the accomplishments and challenges of H1N1 vaccination programs during the 2009-10 influenza season. State and local health departments distributed and administered H1N1 vaccine using a combination of public and private efforts. Challenges encountered during the vaccination campaign included the supply of and demand for vaccine, prioritization strategies, and local logistics. To improve the response capabilities to deal with infectious disease emergencies, the authors recommend investing in technologies that will assure a more timely availability of the needed quantities of vaccine, developing local public health capacity and relationships with healthcare providers, and enhancing federal support of state and local activities. The authors support in principle the CDC recommendation to vaccinate annually all Americans over 6 months of age against seasonal influenza to establish a standard of practice on which to expand the ability to vaccinate during a pandemic. However, expanding seasonal influenza vaccination efforts will be an expensive and long-term investment that will need to be weighed against anticipated benefits and other public health needs. Such investments in public health infrastructure could be important for building capacity and practice for distributing, dispensing, and administering countermeasures in response to a future pandemic or biological weapons attack.     

Monitoring vaccine safety during an influenza pandemic

In the event that a vaccine is available during an influenza pandemic, vaccine safety monitoring will occur as part of comprehensive public health surveillance of the vaccination campaign. Though inactivated influenza vaccines have been widely used in the United States and much is known about their safety profile, attention will need to be paid to both common self-limited adverse reactions and rarer, more serious events that may or may not be causally related to vaccination. The primary surveillance systems used to generate and test hypotheses about vaccine safety concerns are the Vaccine Adverse Event Reporting System (VAERS) and the Vaccine Safety Datalink (VSD), respectively. Examples of recent use of these systems to investigate influenza vaccine safety and enhancements planned for use during a pandemic are presented. Ethical issues that will need to be addressed as part of an overall vaccine safety response include risk communication and injury compensation. Advance planning and the use of available technologic solutions are needed to respond to the scientific and logistic challenges involved in safely implementing mass vaccination during a pandemic.     

Pandemic influenza: overview of vaccines and antiviral drugs

Pandemic influenza has become a high priority item for all public health authorities. An influenza pandemic is believed to be imminent, and scientists agree that it will be a matter of when, where, and what will be the causative agent. Recently, most attention has been directed to human cases of avian influenza caused by a H5N1 avian influenza virus. An effective vaccine will be needed to substantially reduce the impact of an influenza pandemic. Current influenza vaccine manufacturing technology is not adequate to support vaccine production in the event of an avian influenza outbreak, and it has now become clear that new innovative production technology is required. Antiviral drugs, on the other hand, can play a very important role in slowing the disease spread but are in short supply and resistance has been a major issue. Here, we provide an update on the status of pandemic vaccine development and antiviral drugs. Finally, we conclude with some proposed areas of focus in pandemic vaccine preparedness.     

Broadly Protective Adenovirus-Based Multivalent Vaccines against Highly Pathogenic Avian Influenza Viruses for Pandemic Preparedness

Recurrent outbreaks of H5, H7 and H9 avian influenza viruses in domestic poultry accompanied by their occasional transmission to humans have highlighted the public health threat posed by these viruses. Newer vaccine approaches for pandemic preparedness against these viruses are needed, given the limitations of vaccines currently approved for H5N1 viruses in terms of their production timelines and the ability to induce protective immune responses in the absence of adjuvants. In this study, we evaluated the feasibility of an adenovirus (AdV)-based multivalent vaccine approach for pandemic preparedness against H5, H7 and H9 avian influenza viruses in a mouse model. Replication-defective AdV vectors expressing hemagglutinin (HA) from different subtypes and nucleoprotein (NP) from one subtype induced high levels of humoral and cellular immune responses and conferred protection against virus replication following challenge with H5, H7 and H9 avian influenza virus subtypes. Inclusion of HA from the 2009 H1N1 pandemic virus in the vaccine formulation further broadened the vaccine coverage. Significantly high levels of HA stalk-specific antibodies were observed following immunization with the multivalent vaccine. Inclusion of NP into the multivalent HA vaccine formulation resulted in the induction of CD8 T cell responses. These results suggest that a multivalent vaccine strategy may provide reasonable protection in the event of a pandemic caused by H5, H7, or H9 avian influenza virus before a strain-matched vaccine can be produced.     

A TritonX-100-split Virion Influenza Vaccine is Safe and Fulfills the Committee for Proprietary Medicinal Products (CPMP) Recommendations for the European Community for Immunogenicity,in Children,Adults and the Elderly

Influenza epidemics are an important cause of morbidity and mortality throughout the world. Current recommendations from Health Authorities emphasize annual immunization of people who are particularly at risk from an influenza virus infection; however, vaccination of working adults and of school children also has been shown to provide public health benefits. To give it a more advantageous reactogenicity profile than the diethylether-split influenza vaccines available previously, a split virion influenza vaccine has been produced with TritonX-100. In a series of clinical trials, Aventis Pasteur (formerly, Pasteur Mérieux Connaught) tested both the safety and immunogenicity of this TritonX-100-split virion influenza vaccine in 566 subjects (42 children, 296 adults, and 228 elderly adults) during three influenza seasons (1991, 1993, and 1995). The TritonX-100-split virion vaccine was well tolerated: no serious adverse events were recorded during the 21 days following immunization. Among the local reactions observed, mild pain, redness, or induration at the injection site were the most frequently reported. Fever (38·0 to 38·5°C) was noted in five adults or elderly subjects (1%), and in two children (5%). Immunogenicity was determined by measuring serum haemagglutinin antibody titres specific to each vaccine virus strain. In each of the three vaccination campaigns, the TritonX-100-split virion influenza vaccine fulfilled the Notes for Guidance on Harmonization of Requirements for Influenza Vaccines outlined by the Committee for Proprietary Medicinal Products (CPMP) of the European Community for an influenza virus vaccine (i.e., seroprotection, seroconversion, or increase of geometric mean titre) in all age groups.     

Mathematical Modeling of Influenza A Virus Dynamics within Swine Farms and the Effects of Vaccination

Influenza A virus infections are widespread in swine herds across the world. Influenza negatively affects swine health and production, and represents a significant threat to public health due to the risk of zoonotic infections. Swine herds can act as reservoirs for potentially pandemic influenza strains. In this study, we develop mathematical models based on experimental data, representing typical breeding and wean-to-finish swine farms. These models are used to explore and describe the dynamics of influenza infection at the farm level, which are at present not well understood. In addition, we use the models to assess the effectiveness of vaccination strategies currently employed by swine producers, testing both homologous and heterologous vaccines. An important finding is that following an influenza outbreak in a breeding herd, our model predicts a persistently high level of infectious piglets. Sensitivity analysis indicates that this finding is robust to changes in both transmission rates and farm size. Vaccination does not eliminate influenza throughout the breeding farm population. In the wean-to-finish herd, influenza infection may persist in the population only if recovered individuals become susceptible to infection again. A homologous vaccine administered to the entire wean-to-finish population after the loss of maternal antibodies eliminates influenza, but a vaccine that only induces partial protection (heterologous vaccine) has little effect on influenza infection levels. Our results have important implications for the control of influenza in swine herds, which is crucial in order to reduce both losses for swine producers and the risk to public health.     

Community engagement: leadership tool for catastrophic health events

Disasters and epidemics are immense and shocking disturbances that require the judgments and efforts of large numbers of people, not simply those who serve in an official capacity. This article reviews the Working Group on Community Engagement in Health Emergency Planning's recommendations to government decision makers on why and how to catalyze the civic infrastructure for an extreme health event. Community engagement--defined here as structured dialogue, joint problem solving, and collaborative action among formal authorities, citizens at-large, and local opinion leaders around a pressing public matter--can augment officials' abilities to govern in a crisis, improve application of communally held resources in a disaster or epidemic, and mitigate community wide losses. The case of limited medical options in an influenza pandemic serves to demonstrate the civic infrastructure's preparedness, response, and recovery capabilities and to illustrate how community engagement can improve pandemic contingency planning.     

广谱流感疫苗的研究进展

流行性感冒(简称流感)的频频暴发严重危害人类健康和公共卫生,已引起全球范围内的高度关注。预防流感最有效和经济的措施是接种疫苗,但流感病毒的持续变异可逃逸人群已有的免疫应答,目前使用的季节性流感疫苗仅对亚型内抗原匹配较好的毒株产生免疫保护作用,难以有效应对因抗原漂移或抗原转换而产生的无法预料的流感大流行。因此,研发对流感病毒不同亚型均具有交叉免疫保护作用的广谱流感疫苗具有重要意义。近年来,流感病毒广谱中和抗体的发现、对流感病毒抗原保守区域及细胞免疫机制的深入研究、疫苗免疫策略的优化等都为广谱流感疫苗的研发提供了新思路。本文简述了近几年基于血凝素、基质蛋白、核蛋白等多种流感靶抗原的广谱流感疫苗的研究进展。     

Examining Perceptions about Mandatory Influenza Vaccination of Healthcare Workers through Online Comments on News Stories

Background

The aim of this study was to understand online public perceptions of the debate surrounding the choice of annual influenza vaccinations or wearing masks as a condition of employment for healthcare workers, such as the one enacted in British Columbia in August 2012.

Methods

Four national and 82 local (British Columbia) Canadian online news sites were searched for articles posted between August 2012 and May 2013 containing the words “healthcare workers” and “mandatory influenza vaccinations/immunizations” or “mandatory flu shots and healthcare workers.” We included articles from sources that predominantly concerned our topic of interest and that generated reader comments. Two researchers coded the unedited comments using thematic analysis, categorizing codes to allow themes to emerge. In addition to themes, the comments were categorized by: 1) sentiment towards influenza vaccines; 2) support for mandatory vaccination policies; 3) citing of reference materials or statistics; 4) self-identified health-care worker status; and 5) sharing of a personal story.

Results

1163 comments made by 648 commenters responding to 36 articles were analyzed. Popular themes included concerns about freedom of choice, vaccine effectiveness, patient safety, and distrust in government, public health, and the pharmaceutical industry. Almost half (48%) of commenters expressed a negative sentiment toward the influenza vaccine, 28% were positive, 20% were neutral, and 4% expressed mixed sentiment. Of those who commented on the policy, 75% did not support the condition to work policy, while 25% were in favour. Of the commenters, 11% self-identified as healthcare workers, 13% shared personal stories, and 18% cited a reference or statistic.

Interpretation

The perception of the influenza vaccine in the comment sections of online news sites is fairly poor. Public health agencies should consider including online forums, comment sections, and social media sites as part of their communication channels to correct misinformation regarding the benefits of HCW influenza immunization and the effectiveness of the vaccine.     

“Pandemic Public Health Paradox”: Time Series Analysis of the 2009/10 Influenza A / H1N1 Epidemiology,Media Attention,Risk Perception and Public Reactions in 5 European Countries

In 2009, influenza A H₁N₁ caused the first pandemic of the 21^st century. Although a vaccine against this influenza subtype was offered before or at the onset of the second epidemic wave that caused most of the fatal cases in Europe, vaccination rates for that season were lower than expected. We propose that the contradiction between high risk of infection and low use of available prevention measures represents a pandemic public health paradox. This research aims for a better understanding of this paradox by exploring the time-dependent interplay among changing influenza epidemiology, media attention, pandemic control measures, risk perception and public health behavior among five European countries (Czech Republic, Denmark, Germany, Spain and the UK). Findings suggest that asynchronicity between media curves and epidemiological curves may potentially explain the pandemic public health paradox; media attention for influenza A H₁N₁ in Europe declined long before the epidemic reached its peak, and public risk perceptions and behaviors may have followed media logic, rather than epidemiological logic.     

Bulls, Bears, and Birds: Preparing the Financial Industry for an Avian Influenza Pandemic

Bulls, Bears, and Birds: Preparing the Financial Industry for an Avian Influenza Pandemic was a half day symposium on avian influenza for senior leaders and decision makers from the financial sector with responsibility for business continuity, health, and security. The event brought together experts and leaders from the medical, public health, business continuity, and financial communities to appraise financial industry leaders on the threat of avian influenza and to offer suggestions regarding what the financial industry could do to prepare and respond.     

Immunisation against influenza among people aged over 65 living at home in Leicestershire during winter 1991-2.

OBJECTIVES--To assess the size of the elderly population for whom influenza vaccine is indicated and how many are vaccinated. DESIGN--Cohort questionnaire study. SETTING--Leicestershire general practices. SUBJECTS--800 elderly subjects selected a random from the Leicestershire family health services authority list who were not living in residential care, 565 of whom returned a questionnaire. MAIN OUTCOME MEASURES--Patient profile, vaccine offers, vaccination status, and reasons for not accepting vaccine. RESULTS--170 of 334 (51%) people aged 65-74 years and 106 of 205 (52%) aged > or = 75 years had one or more medical indications for influenza vaccine. 195 people were offered vaccine, 49 of whom had no risk factor. 152 offers were made opportunistically during visits to the practice and only six were made in writing or by telephone. Overall 113 of 266 patients with known medical indications were immunised. Vaccine was accepted by 148 of 189 (78%) offered it, and, as judged by acceptance in sequential years, influenza vaccine was well tolerated. The main reasons for not being vaccinated were misconception about risk status and inadequate advice from doctors. CONCLUSIONS--The prevalence of medical indications for vaccine is not large enough to justify a policy of universal immunisation. Most patients offered vaccine accept it and tolerate it well. Improved targeting and education is needed to increase immunisation of people at risk.     

Optimal Vaccine Allocation for the Early Mitigation of Pandemic Influenza

With new cases of avian influenza H5N1 (H5N1AV) arising frequently, the threat of a new influenza pandemic remains a challenge for public health. Several vaccines have been developed specifically targeting H5N1AV, but their production is limited and only a few million doses are readily available. Because there is an important time lag between the emergence of new pandemic strain and the development and distribution of a vaccine, shortage of vaccine is very likely at the beginning of a pandemic. We coupled a mathematical model with a genetic algorithm to optimally and dynamically distribute vaccine in a network of cities, connected by the airline transportation network. By minimizing the illness attack rate (i.e., the percentage of people in the population who become infected and ill), we focus on optimizing vaccine allocation in a network of 16 cities in Southeast Asia when only a few million doses are available. In our base case, we assume the vaccine is well-matched and vaccination occurs 5 to 10 days after the beginning of the epidemic. The effectiveness of all the vaccination strategies drops off as the timing is delayed or the vaccine is less well-matched. Under the best assumptions, optimal vaccination strategies substantially reduced the illness attack rate, with a maximal reduction in the attack rate of 85%. Furthermore, our results suggest that cooperative strategies where the resources are optimally distributed among the cities perform much better than the strategies where the vaccine is equally distributed among the network, yielding an illness attack rate 17% lower. We show that it is possible to significantly mitigate a more global epidemic with limited quantities of vaccine, provided that the vaccination campaign is extremely fast and it occurs within the first weeks of transmission.     

MHC Class I-Presented T Cell Epitopes Identified by Immunoproteomics Analysis Are Targets for a Cross Reactive Influenza-Specific T Cell Response

Influenza virus infection and the resulting complications are a significant global public health problem. Improving humoral immunity to influenza is the target of current conventional influenza vaccines, however, these are generally not cross-protective. On the contrary, cell-mediated immunity generated by primary influenza infection provides substantial protection against serologically distinct viruses due to recognition of cross-reactive T cell epitopes, often from internal viral proteins conserved between viral subtypes. Efforts are underway to develop a universal flu vaccine that would stimulate both the humoral and cellular immune responses leading to long-lived memory. Such a universal vaccine should target conserved influenza virus antibody and T cell epitopes that do not vary from strain to strain. In the last decade, immunoproteomics, or the direct identification of HLA class I presented epitopes, has emerged as an alternative to the motif prediction method for the identification of T cell epitopes. In this study, we used this method to uncover several cross-specific MHC class I specific T cell epitopes naturally presented by influenza A-infected cells. These conserved T cell epitopes, when combined with a cross-reactive antibody epitope from the ectodomain of influenza M2, generate cross-strain specific cell mediated and humoral immunity. Overall, we have demonstrated that conserved epitope-specific CTLs could recognize multiple influenza strain infected target cells and, when combined with a universal antibody epitope, could generate virus specific humoral and T cell responses, a step toward a universal vaccine concept. These epitopes also have potential as new tools to characterize T cell immunity in influenza infection, and may serve as part of a universal vaccine candidate complementary to current vaccines.     

Heterosubtypic antibody response elicited with seasonal influenza vaccine correlates partial protection against highly pathogenic H5N1 virus

Background

The spread of highly pathogenic avian influenza (HPAI) H5N1 virus in human remains a global health concern. Heterosubtypic antibody response between seasonal influenza vaccine and potential pandemic influenza virus has important implications for public health. Previous studies by Corti et al. and by Gioia et al. demonstrate that heterosubtypic neutralizing antibodies against the highly pathogenic H5N1 virus can be elicited with a seasonal influenza vaccine in humans. However, whether such response offers immune protection against highly pathogenic H5N1 virus remained to be determined.

Methodology/Principal Findings

In this study, using a sensitive influenza HA (hemagglutinin) and NA (neuraminidase) pseudotype-based neutralization (PN) assay we first confirmed that low levels of heterosubtypic neutralizing antibody response against H5N1 virus were indeed elicited with seasonal influenza vaccine in humans. We then immunized mice with the seasonal influenza vaccine and challenged them with lethal doses of highly pathogenic H5N1 virus. As controls, we immunized mice with homosubtypic H5N1 virus like particles (VLP) or PBS and challenged them with the same H5N1 virus. Here we show that low levels of heterosubtypic neutralizing antibody response were elicited with seasonal influenza vaccine in mice, which were significantly higher than those in PBS control. Among them 2 out of 27 whose immune sera exhibited similar levels of neutralizing antibody response as VLP controls actually survived from highly pathogenic H5N1 virus challenge.

Conclusions/Significance

Therefore, we conclude that low levels of heterosubtypic neutralizing antibody response are indeed elicited with seasonal influenza vaccine in humans and mice and at certain levels such response offers immune protection against severity of H5N1 virus infection.     

Assessment of Local Public Health Workers' Willingness to Respond to Pandemic Influenza through Application of the Extended Parallel Process Model

Background

Local public health agencies play a central role in response to an influenza pandemic, and understanding the willingness of their employees to report to work is therefore a critically relevant concern for pandemic influenza planning efforts. Witte''s Extended Parallel Process Model (EPPM) has been found useful for understanding adaptive behavior in the face of unknown risk, and thus offers a framework for examining scenario-specific willingness to respond among local public health workers. We thus aim to use the EPPM as a lens for examining the influences of perceived threat and efficacy on local public health workers'' response willingness to pandemic influenza.

Methodology/Principal Findings

We administered an online, EPPM-based survey about attitudes/beliefs toward emergency response (Johns Hopkins∼Public Health Infrastructure Response Survey Tool), to local public health employees in three states between November 2006 – December 2007. A total of 1835 responses were collected for an overall response rate of 83%. With some regional variation, overall 16% of the workers in 2006-7 were not willing to “respond to a pandemic flu emergency regardless of its severity”. Local health department employees with a perception of high threat and high efficacy – i.e., those fitting a ‘concerned and confident’ profile in the EPPM analysis – had the highest declared rates of willingness to respond to an influenza pandemic if required by their agency, which was 31.7 times higher than those fitting a ‘low threat/low efficacy’ EPPM profile.

Conclusions/Significance

In the context of pandemic influenza planning, the EPPM provides a useful framework to inform nuanced understanding of baseline levels of – and gaps in – local public health workers'' response willingness. Within local health departments, ‘concerned and confident’ employees are most likely to be willing to respond. This finding may allow public health agencies to design, implement, and evaluate training programs focused on emergency response attitudes in health departments.     

A Review of the Evidence to Support Influenza Vaccine Introduction in Countries and Areas of WHO's Western Pacific Region

Background

Immunization against influenza is considered an essential public health intervention to control both seasonal epidemics and pandemic influenza. According to the World Health Organization (WHO), there are five key policy and three key programmatic issues that decision-makers should consider before introducing a vaccine. These are (a) public health priority, (b) disease burden, (c) efficacy, quality and safety of the vaccine, (d) other inventions, (e) economic and financial issues, (f) vaccine presentation, (g) supply availability and (h) programmatic strength. We analyzed the body of evidence currently available on these eight issues in the WHO Western Pacific Region.

Methodology/Principal Findings

Studies indexed in PubMed and published in English between 1 January 2000 and 31 December 2010 from the 37 countries and areas of the Western Pacific Region were screened for keywords pertaining to the five policy and three programmatic issues. Studies were grouped according to country income level and vaccine target group. There were 133 articles that met the selection criteria, with most (90%) coming from high-income countries. Disease burden (n = 34), vaccine efficacy, quality and safety (n = 27) and public health priority (n = 27) were most frequently addressed by studies conducted in the Region. Many studies assessed influenza vaccine policy and programmatic issues in the general population (42%), in the elderly (24%) and in children (17%). Few studies (2%) addressed the eight issues relating to pregnant women.

Conclusions/Significance

The evidence for vaccine introduction in countries and areas in this Region remains limited, particularly in low- and middle-income countries that do not currently have influenza vaccination programmes. Surveillance activities and specialized studies can be used to assess the eight issues including disease burden among vaccine target groups and the cost-effectiveness of influenza vaccine. Multi-country studies should be considered to maximize resource utilization for cross-cutting issues such as vaccine presentation and other inventions.     

Functional Testing of an Inhalable Nanoparticle Based Influenza Vaccine Using a Human Precision Cut Lung Slice Technique

Annual outbreaks of influenza infections, caused by new influenza virus subtypes and high incidences of zoonosis, make seasonal influenza one of the most unpredictable and serious health threats worldwide. Currently available vaccines, though the main prevention strategy, can neither efficiently be adapted to new circulating virus subtypes nor provide high amounts to meet the global demand fast enough. New influenza vaccines quickly adapted to current virus strains are needed. In the present study we investigated the local toxicity and capacity of a new inhalable influenza vaccine to induce an antigen-specific recall response at the site of virus entry in human precision-cut lung slices (PCLS). This new vaccine combines recombinant H1N1 influenza hemagglutinin (HAC1), produced in tobacco plants, and a silica nanoparticle (NP)-based drug delivery system. We found no local cellular toxicity of the vaccine within applicable concentrations. However higher concentrations of NP (≥10³ µg/ml) dose-dependently decreased viability of human PCLS. Furthermore NP, not the protein, provoked a dose-dependent induction of TNF-α and IL-1β, indicating adjuvant properties of silica. In contrast, we found an antigen-specific induction of the T cell proliferation and differentiation cytokine, IL-2, compared to baseline level (152±49 pg/mg vs. 22±5 pg/mg), which could not be seen for the NP alone. Additionally, treatment with 10 µg/ml HAC1 caused a 6-times higher secretion of IFN-γ compared to baseline (602±307 pg/mg vs. 97±51 pg/mg). This antigen-induced IFN-γ secretion was further boosted by the adjuvant effect of silica NP for the formulated vaccine to a 12-fold increase (97±51 pg/mg vs. 1226±535 pg/mg). Thus we were able to show that the plant-produced vaccine induced an adequate innate immune response and re-activated an established antigen-specific T cell response within a non-toxic range in human PCLS at the site of virus entry.     

Emulsified Nanoparticles Containing Inactivated Influenza Virus and CpG Oligodeoxynucleotides Critically Influences the Host Immune Responses in Mice

Background

Antigen sparing and cross-protective immunity are regarded as crucial in pandemic influenza vaccine development. Both targets can be achieved by adjuvantation strategy to elicit a robust and broadened immune response. We assessed the immunogenicity of an inactivated H5N1 whole-virion vaccine (A/Vietnam/1194/2004 NIBRG-14, clade 1) formulated with emulsified nanoparticles and investigated whether it can induce cross-clade protecting immunity.

Methodology/Principal Findings

After formulation with PELC, a proprietary water-in-oil-in-water nanoemulsion comprising of bioresorbable polymer/Span®85/squalene, inactivated virus was intramuscularly administered to mice in either one-dose or two-dose schedule. We found that the antigen-specific serum antibody responses elicited after two doses of non-adjuvanted vaccine were lower than those observed after a single dose of adjuvanted vaccine, PELC and the conventional alum adjuvant as well. Moreover, 5 µg HA of PELC-formulated inactivated virus were capable of inducing higher antibodies than those obtained from alum-adjuvanted vaccine. In single-dose study, we found that encapsulating inactivated virus into emulsified PELC nanoparticles could induce better antibody responses than those formulated with PELC-adsorbed vaccine. However, the potency was rather reduced when the inactivated virus and CpG (an immunostimulatory oligodeoxynucleotide containing unmethylated cytosine-guanosine motifs) were co-encapsulated within the emulsion. Finally, the mice who received PELC/CpG(adsorption)-vaccine could easily and quickly reach 100% of seroprotection against a homologous virus strain and effective cross-protection against a heterologous virus strain (A/Whooper swan/Mongolia/244/2005, clade 2.2).

Conclusions/Significance

Encapsulating inactivated H5N1 influenza virus and CpG into emulsified nanoparticles critically influences the humoral responses against pandemic influenza. These results demonstrated that the use of PELC could be as antigen-sparing in preparation for a potential shortage of prophylactic vaccines against local infectious diseases, in particular pandemic influenza. Moreover, the cross-clade neutralizing antibody responses data verify the potential of such adjuvanted H5N1 candidate vaccine as an effective tool in pre-pandemic preparedness.