Table of Contents

Volume 8, Issue 1

  January 2012

  Pages 1 - 145

Special Focus: Influenza Vaccines

 

Guest Editor: Dr. Susanna

Esposito (University of Milan, Italy)

 

 

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 Issue Catalogue (MARC XML)

EDITOR'S CORNER

Open Access Article

Letter from the Editor

Ronald W. Ellis and Eva M. Riedmann
Page 1
http://dx.doi.org/10.4161/hv.8.1.19091
Full Text | PDF




NEWS, POLICY AND PROFILES

Open Access Article

Human Vaccines & Immunotherapeutics: News

Eva M. Riedmann
Pages 2 - 5
http://dx.doi.org/10.4161/hv.8.1.19092
Abstract | Full Text | PDF

Multi-mechanistic oncolytic poxvirus JX-594 provides survival benefit for liver cancer patients
Therapeutic HCV vaccine confers substantial viral suppression in Hep C patients 
Brain cancer vaccine rindopepimut increases survival in Phase II  
FDA experts back Prevnar 13 for adults over 50 years
PANVAC shows promise for metastatic breast and ovarian cancers 
Norovirus vaccine protects against illness in humans 
First synthetic nanoparticle vaccine reaches human studies 
GAVI to bring HPV and rubella vaccines to developing countries 






EDITOR'S CORNER

Open Access Article

Special Focus: Influenza vaccines

Susanna Esposito
Page 6
http://dx.doi.org/10.4161/hv.8.1.19169
Full Text | PDF




SPECIAL FOCUS REVIEWS

Open Access Article

Influenza viruses: From birds to humans

Leslie A. Reperant, Thijs Kuiken and Albert D.M.E. Osterhaus
Pages 7 - 16
http://dx.doi.org/10.4161/hv.8.1.18672
Abstract | Full Text | PDF

Avian influenza viruses are the precursors of human influenza A viruses. They may be transmitted directly from avian reservoirs, or infect other mammalian species before subsequent transmission to their human host. So far, avian influenza viruses have caused sporadic—yet increasingly more frequently recognized—cases of infection in humans. They have to adapt to and circulate efficiently in human populations, before they may trigger a worldwide human influenza outbreak or pandemic. Cross-species transmission of avian influenza viruses from their reservoir hosts—wild waterbirds—to terrestrial poultry and to humans is based on different modes of transmission and results in distinctive pathogenetic manifestations, which are reviewed in this paper.

Open Access Article

Clinical and socioeconomic impact of pediatric seasonal and pandemic influenza

Paola Marchisio, Elena Baggi, Sonia Bianchini, Nicola Principi and Susanna Esposito
Pages 17 - 20
http://dx.doi.org/10.4161/hv.8.1.18145
Abstract | Full Text | PDF

Influenza is frequent among otherwise healthy day-care and school-aged children. Recent studies have demonstrated its significant effect on various outcome factors, including significantly more school and parental work absenteeism, and secondary illnesses among family members. Other studies have shown that the potential benefit of vaccinating children against influenza extends to other members of their families, thus supporting earlier economic modeling analyses of immunization programs. Although there are some differences in the clinical and socio-economic impact of seasonal and pandemic influenza, the benefits of vaccination are similar in both cases. The vaccination of otherwise healthy children may significantly reduce direct and indirect influenza-related costs, which supports the recommendation to make wider use of influenza vaccine in healthy children of any age in order to reduce the burden of infection on the community.

Open Access Article

Clinical and socioeconomic impact of seasonal and pandemic influenza in adults and the elderly

Roberto Gasparini, Daniela Amicizia, Piero Luigi Lai and Donatella Panatto
Pages 21 - 28
http://dx.doi.org/10.4161/hv.8.1.17622
Abstract | Full Text | PDF

Influenza epidemics and pandemics carry a heavy socioeconomic burden. Hospitalization and treatment are more often necessary in high-risk patients, such as the elderly. However, the impact of influenza is not negligible even in adults, mainly because of lost productivity. The World Health Organization estimates that seasonal influenza causes 250,000–500,000 deaths worldwide each year; however, mortality may be very high in pandemic periods.

 

Many estimates of the costs of seasonal influenza have been made in various socioeconomic contexts. For instance, among the adult population in Italy, a cost of €940.39 per case has been estimated. In the US, the average annual influenza burden in 18–49-y-old adults without underlying medical conditions is judged to include approximately 32,000 hospitalizations and 680 deaths. Estimating the influenza burden is a useful aid to determining the best influenza vaccination strategy and preventive and clinical treatments.

Open Access Article

Clinical and laboratory diagnosis of influenza

Carlos Rodrigo and Maria Me´ndez
Pages 29 - 33
http://dx.doi.org/10.4161/hv.8.1.18924
Abstract | Full Text | PDF

The clinical diagnosis of influenza can be very difficult or rather easy depending on the circumstances. It's easy when the epidemiological context is appropriate; the patient is a school kid or a teenager, and the symptoms are typical. On the other hand, it is hard when it fails to match any of the above premises, the more imformation that is missing, the more difficult it becomes. The symptomatology is correlated with age; therefore, typical clinical manifestations are only referred from 3–4 y old: rhinitis, fever with or without chills, cough, headache, joint and muscle pain and malaise. The patient often says he/she “feels sick” but his/her general condition is not at all serious. A rapid influenza diagnosis has been shown to reduce unnecessary test and antibiotics in pediatric patients and allows rational use of antivirals, early discharge from emergency departments and hospital wards, appropriate infection control measures and cohorting of infected patients. Tests that yield results in a timely manner that can influence clinical management are recommended to guide patient care. Results of testing should take into account the a priori likelihood of influenza infection based on the patient’s signs and symptoms, the sensitivity and specificity of the test used, and information on circulation of influenza in the community. Failing to use the option of microbiological diagnosis when appropriate is a missed opportunity that can generate anxiety without justification, avoid unnecessarily antibiotics, omit antiviral therapy when convenient, and a teaching possibility.

Open Access Article

Correlates of vaccine protection from influenza and its complications

Jonathan A. McCullers and Victor C. Huber
Pages 34 - 44
http://dx.doi.org/10.4161/hv.8.1.18214
Abstract | Full Text | PDF

Despite use of influenza vaccines for more than 65 y, influenza and its complications are a major cause of morbidity and mortality worldwide. Most deaths during influenza virus infections are due to underlying co-morbidities or secondary bacterial pneumonia. The measures of immune response currently used for licensure of influenza vaccines are relevant mainly for protection from viral infection in healthy adults. Development of new or improved influenza vaccines will require a definition of novel, and specific correlates of protection. These correlates should associate immune responses with outcomes that are relevant to specific risk groups, such as asthma exacerbation, hospitalization or disruptions to care or daily activities. Assessment of vaccine effectiveness for both viral and bacterial vaccines should include measures of impact on secondary bacterial pneumonia.

Open Access Article

New technologies for influenza vaccines

Philip Dormitzer, Theodore Tsai and Giuseppe Del Giudice
Pages 45 - 58
http://dx.doi.org/10.4161/hv.8.1.18859
Abstract | Full Text | PDF

Influenza vaccine preparations have been administered to humans since the late 1930s,¹ and the diversity of approaches in licensed trivalent seasonal or monovalent pandemic products is unparalleled by vaccines against any other target. These approaches include inactivated whole virus vaccines, detergent or solvent “split” vaccines, subunit vaccines, live attenuated vaccines, adjuvanted vaccines, intramuscular vaccines, intradermal vaccines, intranasal vaccines, egg-produced vaccines and mammalian cell culture-produced vaccines. The challenges of influenza immunization, including multiple co-circulating strains, antigenic change over time, a broad age spectrum of disease, and the threat of pandemics, continue to drive the development of new approaches. This review describes some of the new approaches to influenza immunization that are the subjects of active research and development.

Open Access Article

Adjuvanted influenza vaccines

Nicola Principi and Susanna Esposito
Pages 59 - 66
http://dx.doi.org/10.4161/hv.8.1.18011
Abstract | Full Text | PDF

The search for adjuvants has been stimulated by the need to ensure greater protection against influenza among subjects who show a reduced immune response to conventional influenza vaccines. Aluminum salts have long been used but are not considered satisfactory. This has led to the development of other possible compounds, sometimes on the basis of new knowledge concerning the mechanisms regulating the immune response to infections. Some of the new adjuvants (emulsions and virosomes) have been widely evaluated, and the apparently good results have led to the registration of adjuvanted influenza vaccines for use in humans, at least in some countries and in some subjects. In other cases, the adjuvants have been mainly or exclusively studied in experimental animals, and are unlikely to be used in humans in the near future. However, even in the case of those for which a considerable amount of data are available, assessments of their superiority over conventional influenza vaccines have mainly been based on immunogenicity studies, and have not been confirmed by comparative, randomized, double-blind clinical trials. Moreover, the very few human data comparing different adjuvants are frequently conflicting. The aim of this review is to discuss the characteristics and advantages of the adjuvants that have so far been used and to describe some of the new adjuvants that are still in the development phase.

Open Access Article

Current evidence on intradermal influenza vaccines administered by Soluvia™ licensed micro injection system

Giancarlo Icardi, Andrea Orsi, Antonella Ceravolo and Filippo Ansaldi
Pages 67 - 75
http://dx.doi.org/10.4161/hv.8.1.18419
Abstract | Full Text | PDF

Among the several strategies explored for (1) the enhancement of the immune response to influenza immunization, (2) the improvement of the vaccine acceptability and (3) the overcoming of the egg-dependency for vaccine production, intradermal administration of influenza vaccine emerges as a promising alternative to conventional intramuscular route, thanks to the recent availability of new delivery devices and the perception of advantages in terms of immunogenicity, safety, reduction of antigen content and acceptability.

 

Data from clinical trials performed in children, adults <60 y and elderly people and post-marketing surveillance demonstrate that actually, licensed intradermal influenza vaccines, Intanza™ 9 and 15 µg and Fluzone™ Intradermal, administered by the microinjection system Soluvia™, show an excellent acceptability, tolerability and safety profile. Formulations containing 9 and 15 μg per strain demonstrate, respectively, comparable and superior immunogenicity than conventional intramuscular vaccines. Licensed intradermal influenza vaccines can be considered a valid alternative to standard intramuscular vaccination offering significant advantages in low-responder populations and helping to increase influenza vaccination coverage rates especially in people with fear of needles or high apprehension associated with annual vaccination.

Open Access Article

Live attenuated intranasal influenza vaccine

Susanna Esposito, Valentina Montinaro, Elena Groppali, Rossana Tenconi, Margherita Semino and Nicola Principi
Pages 76 - 80
http://dx.doi.org/10.4161/hv.8.1.18809
Abstract | Full Text | PDF

Annual vaccination is the most effective means of preventing and controlling influenza epidemics, and the traditional trivalent inactivated vaccine (TIV) is by far the most widely used. Unfortunately, it has a number of limitations, the most important of which is its poor immunogenicity in younger children and the elderly, the populations at greatest risk of severe influenza. Live attenuated influenza vaccine (LAIV) has characteristics that can overcome some of these limitations. It does not have to be injected because it is administered intranasally. It is very effective in children and adolescents, among whom it prevents significantly more cases of influenza than the traditional TIV. However, its efficacy in adults has not been adequately documented, which is why it has not been licensed for use by adults by the European health authorities. LAIV is safe and well tolerated by children aged > 2 y and adults, but some concerns arisen regarding its safety in younger children and subjects with previous asthma or with recurrent wheezing. Further studies are needed to solve these problems and to evaluate the possible role of LAIV in the annual vaccination of the general population.

Open Access Article

The rationale for quadrivalent influenza vaccines

Christopher S. Ambrose and Myron J. Levin
Pages 81 - 88
http://dx.doi.org/10.4161/hv.8.1.17623
Abstract | Full Text | PDF

Two antigenically distinct lineages of influenza B viruses have circulated globally since 1985. However, licensed trivalent seasonal influenza vaccines contain antigens from only a single influenza B virus and thus provide limited immunity against circulating influenza B strains of the lineage not present in the vaccine. In recent years, predictions about which B lineage will predominate in an upcoming influenza season have been no better than chance alone, correct in only 5 of the 10 seasons from 2001 to 2011. Consequently, seasonal influenza vaccines could be improved by inclusion of influenza B strains of both lineages. The resulting quadrivalent influenza vaccines would allow influenza vaccination campaigns to respond more effectively to current global influenza epidemiology. Manufacturing capacity for seasonal influenza vaccines has increased sufficiently to supply quadrivalent influenza vaccines, and methods to identify the influenza B strains to include in such vaccines are in place. Multiple manufacturers have initiated clinical studies of quadrivalent influenza vaccines. Data from those studies, taken together with epidemiologic data regarding the burden of disease caused by influenza B infections, will determine the safety, effectiveness, and benefit of utilizing quadrivalent vaccines for the prevention of seasonal influenza disease.

Open Access Article

The importance of influenza prevention for public health

Paloma Carrillo-Santisteve, Bruno Christian Ciancio, Angus Nicoll and Pier Luigi Lopalco
Pages 89 - 95
http://dx.doi.org/10.4161/hv.8.1.19066
Abstract | Full Text | PDF

Annual epidemics of seasonal (inter-pandemic) influenza represent a significant burden on society in terms of morbidity, mortality, hospitalizations and lost working time. The impact of influenza depends on a mix of direct and indirect effects and is not easy to assess. Nevertheless there is a consensus in considering influenza prevention and mitigation high priorities for public health. We review the available evidence to assess the impact of influenza prevention focusing especially on vaccines and immunization strategies.

Open Access Article

Influenza vaccination for older adults

H. Keipp B. Talbot, Romina Libster and Kathryn Edwards
Pages 96 - 101
http://dx.doi.org/10.4161/hv.8.1.18129
Abstract | Full Text | PDF

Influenza vaccines were developed in the 1930s and were shown in randomized clinical trials to prevent influenza in young healthy adults. The significant morbidity and mortality associated with influenza in adults, age 65 y and older, prompted the early recommendation for influenza vaccination in that age group, based on efficacy data in younger adults. Subsequently a number of studies have demonstrated vaccine effectiveness in older adults, but it appears to be lower than in younger adults. New vaccines are being developed with enhanced immunogenicity to improve the protection of older adults. In the meantime, the currently licensed influenza vaccines need to be administered annually to prevent the estimated 90,000 hospitalizations and 5,000 deaths attributed to influenza in adults ≥65 y of age each year.

Open Access Article

Recommendations for the use of influenza vaccine in pediatrics

Susanna Esposito, Valentina Montinaro, Samantha Bosis, Claudia Tagliabue, Elena Baggi and Nicola Principi
Pages 102 - 106
http://dx.doi.org/10.4161/hv.8.1.17957
Abstract | Full Text | PDF

Every year for the last few decades, the health authorities of most countries throughout the world have issued specific recommendations for the prevention and treatment of pediatric influenza, including recommendations concerning the use of vaccines. However, different evaluations of the importance of the disease and the efficacy of influenza vaccination frequently lead to conflicting recommendations. This is clearly demonstrated not only by the differences in the subjects for whom the vaccine is recommended, but also by the inaccurate manner in which subjects at risk of influenza-related complications are defined. Only further studies that consider the burden of the disease and vaccine efficacy in adequate numbers of healthy children and high-risk children with different chronic underlying diseases can overcome all of the current limitations and significantly improve vaccination coverage in both categories.

Open Access Article

Influenza vaccination coverage rate in children: Reasons for a failure and how to go forward

Catherine Weil Olivier
Pages 107 - 118
http://dx.doi.org/10.4161/hv.8.1.18278
Abstract | Full Text | PDF

Based on an increasingly extensive literature expressing the large interest in the field, this paper gives an overview of different aspects of influenza prevention in children. It relies on paradoxes. First, the heaviest part of the burden is well demonstrated in the youngest infants by numerous epidemiological data elsewhere. On the contrary, with older children, the prevention by influenza vaccines is more efficacious—without notable side effects. Second, the available TIV vaccines are 60 years old and the requests of registration and regulation of vaccines have evolved. There is a specific need in children: it is time to re-discuss the pragmatic utilization of influenza vaccines (full dose in the youngest patient? More flexibility regarding the interval between the two required doses in vaccine-naïve children), and to change from a compassionate use to a targeted research and adapted vaccines considering the limits of TIV in the youngest children. Third, influenza virus transmission is the highest in children in semi-close communities (day-care centers, schools), diffusing to households and more largely to the population. A restricted policy on high risk groups (roughly 10% in a pediatric population, all medical conditions including asthma, for whom influenza vaccine coverage is a 15–75% range) is far below the estimated threshold of 45% coverage rate to limit the virus circulation by an indirect impact during seasonal epidemics. Fourth, public health decisions in the vaccination field are usually taken from top to bottom. The pandemic A/H1N1 has toughly demonstrated that “forgetting” about the perception and expectations of the public and the parents nearly created conflicts and at least a strong resistance impeding the quality of a program worked on for a long time ahead. Fifth, and not the least, HCPs are pivotal in influenza vaccination mostly trusted by the parents. Too often, they are not backed by a national and clear support and they need to reinforce their knowledge on the disease and the vaccines.

Open Access Article

Economic value of influenza vaccination

Chiara de Waure, Maria Assunta Veneziano, Chiara Cadeddu, Silvio Capizzi, Maria Lucia Specchia, Stefano Capri and Walter Ricciardi
Pages 119 - 129
http://dx.doi.org/10.4161/hv.8.1.18420
Abstract | Full Text | PDF

Influenza epidemics are responsible for high mortality and morbidity rates in particular among elderly and high risk groups. This review is aimed at assessing the economic value of vaccination in these groups. A search of full economic evaluations of influenza vaccination in comparison with no interventions was performed on PubMed from January 1990 to May 2011. Only economic evaluations dealing with elderly and high risk groups were considered. The quality of selected articles was assessed through Drummond’s checklist. Sixteen cost-effectiveness analyses and four cost-benefit analyses were included: overall, the quality of studies was fairly good. The vaccination was demonstrated to be cost-effective or cost-saving in almost all studies, independently by the perspective and the type of analysis. Influenza vaccination is a worthwhile intervention from the pharmacoeconomic view-point, anyway a standardization of methods should be desirable in order to guarantee the comparability and transferability of results.

Open Access Article

Benefits to mother and child of influenza vaccination during pregnancy

Saad B. Omer, Robert A. Bednarczyk, Shabir A. Madhi and Keith P. Klugman
Pages 130 - 137
http://dx.doi.org/10.4161/hv.8.1.18601
Abstract | Full Text | PDF

Influenza virus infection contributes to substantial morbidity and mortality globally. Included in the list of groups at higher risk of either influenza infection or severe complications following influenza infection are pregnant women and their newborns. Influenza vaccination offers a safe and effective means to prevent or lessen the severity of influenza infections. Recent research has helped elucidate the impact of influenza infection and vaccination on pregnant women and their newborn children and young infants. This review summarizes recent findings in this area and identifies additional gaps in the evidence base that need to be addressed to appropriately inform vaccination policies worldwide, to protect pregnant women and their children from influenza and related complications.

Open Access Article

Ten lessons for the next influenza pandemic—an English perspective : A personal reflection based on community surveillance data

Douglas M. Fleming and Hayley Durnall
Pages 138 - 145
http://dx.doi.org/10.4161/hv.8.1.18808
Abstract | Full Text | PDF

We review experience in England of the swine flu pandemic between May 2009 and April 2010. The surveillance data from the Royal College of General Practitioners Weekly Returns Service and the linked virological data collected in the integrated program with the Health Protection Agency are used as a reference frame to consider issues emerging during the pandemic. Ten lessons are summarized. (1) Delay between illness onset in the first worldwide cases and virological diagnosis restricted opportunities for containment by regional prophylaxis. (2) Pandemic vaccines are unlikely to be available for effective prevention during the first wave of a pandemic. (3) Open, realistic and continuing communication with the public is important. (4) Surveillance programs should be continued through summer as well as winter. (5) Severity of illness should be incorporated in pandemic definition. (6) The reliability of diagnostic tests as used in routine clinical practice calls for further investigation. (7) Evidence from serological studies is not consistent with evidence based on health care requests made by sick persons and is thus of limited value in cost effectiveness studies. (8) Pregnancy is an important risk factor. (9) New strategies for administering vaccines need to be explored. (10) Acceptance by the public and by health professionals of influenza vaccination as the major plank on which the impact of influenza is controlled has still not been achieved.