Immunogenicity and safety of seasonal and 2009 pandemic A/H1N1 influenza vaccines for patients with autoimmune diseases: a prospective, monocentre trial on 199 patients

The 2009 pandemic A/H1N1 influenza outbreak represented a theoretical risk for patients with autoimmune diseases (AID), especially those immunosuppressed. This study was undertaken to evaluate immunogenicity and tolerance of seasonal (SFV) and A/H1N1 flu vaccines (HFV) in AID patients.

Process engineering aspects of plasmid-based biopharmaceuticals production : tackling the threatening vaccine shortages to prevent global pandemics

Infectious diseases such as SARS, influenza and bird flu have the potential to cause global pandemics; a key intervention will be vaccination. Hence, it is imperative to have in place the capacity to create vaccines against new diseases in the shortest time possible. In 2004, The Institute of Medicine asserted that the world is tottering on the verge of a colossal influenza outbreak. The institute stated that, inadequate production system for influenza vaccines is a major obstruction in the preparation towards influenza outbreaks. Because of production issues, the vaccine industry is facing financial and technological bottlenecks: In October 2004, the FDA was caught off guard by the shortage of flu vaccine, caused by a contamination in a US-based plant (Chiron Corporation), one of the only two suppliers of US flu vaccine. Due to difficulties in production and long processing times, the bulk of the world's vaccine production comes from very small number of companies compared to the number of companies producing drugs. Conventional vaccines are made of attenuated or modified forms of viruses. Relatively high and continuous doses are administered when a non-viable vaccine is used and the overall protective immunity obtained is ephemeral. The safety concerns of viral vaccines have propelled interest in creating a viable replacement that would be more effective and safer to use.

Étude sur les déterminants psychosociaux de la vaccination contre le virus A(H1N1) auprès des parents d’enfants qui fréquentent des services de garde éducatifs de Montréal

Introduction En juin 2009, l’Organisation Mondiale de la Santé (OMS) a déclaré l’état de pandémie pour le nouveau virus influenza A(H1N1). Malgré les recommandations des autorités de santé publique, lors de la mise en place de la campagne de vaccination de masse au Québec contre ce virus pandémique, certains groupes de la population ont été plus enclins à être vaccinés que d’autres groupes. Ceci souligne l’importance des déterminants psychosociaux du comportement humain, sujet qui a donné cadre à notre étude. Objectifs Le but de cette étude a été de documenter les attitudes, les connaissances et les influences sociales des parents dont les enfants fréquentent des services de garde éducatifs (SGE) vis-à-vis la vaccination contre la pandémie ainsi que la couverture vaccinale. Méthodologie Un questionnaire auto-administré et anonyme basé sur la théorie des comportements interpersonnels de Triandis a été distribué aux parents d’enfants âgés de 0-59 mois de neuf centres de la petite enfance sur l’île de Montréal. Résultats Le taux de réponse de l’enquête a été de 32,0% (N=185). Le taux de vaccination des enfants s’est retrouvé à 83,4%; ceci représente une couverture plus élevée que la moyenne régionale et nationale. Toutefois, à une question sur l’intention des parents face à une autre pandémie, seuls 46% des parents feraient vacciner leur enfant. Les facteurs les plus significatifs associés à la vaccination de leur enfant ont été les croyances personnelles positives, de bonnes habitudes vaccinales et l’influence des média, tous mesurés par plusieurs indicateurs (RC respectifs de 7,7, 3,1 et 4,2, p<0,05). Conclusion Pour la grippe A(H1N1), plusieurs facteurs contextuels ont joué en faveur des taux de vaccination acceptables chez les enfants. Toutefois, la mise en place d’une campagne de la vaccination par les instances gouvernementales et de santé publique en utilisant divers média pourraient contribuer à un taux de vaccination encore plus élevé en cas d’épidémie ou de pandémie.

Use of intranet and other interventions to increase influenza vaccination among health care workers

Influenza (the flu) is a serious respiratory illness that can cause severe complications, often leading to hospitalization and even death. Influenza epidemics occur in most countries every year, usually during the winter months. Despite recommendations from the Centers for Disease Control and Prevention (CDC) and efforts by health care institutions across the United States, influenza vaccination rates among health care workers in the United States remain low. How to increase the number of vaccinated health care workers is an important public health question and is examined in two journal articles included here. ^ The first journal article evaluates the effectiveness of an Intranet intervention in increasing the proportion of health care workers (HCWs) who received influenza vaccination. Hospital employees were required go to the hospital's Intranet and select "vaccine received," "contraindicated," or "declined" from the online questionnaire. Declining employees automatically received an online pop-up window with education about vaccination; managers were provided feedback on employees' participation rates via e-mail messages. Employees were reminded of the Intranet requirement in articles in the employee newsletter and on the hospital's Intranet. Reminders about the Intranet questionnaire were provided through managers and newsletters to the HCWs. Fewer than half the employees (43.7%) completed the online questionnaire. Yet the hospital witnessed a statistically significant increase in the percentage of employees who received the flu vaccine at the hospital – 48.5% in the 2008-09 season as compared to 36.5%, 38.5% and 29.8% in the previous three years (P < 0.05). ^ The second article assesses current interventions employed by hospitals, health systems and nursing homes to determine which policies have been the most effective in boosting vaccination rates among American health care workers. A systematic review of research published between January 1994 and March 2010 suggests that education is necessary but not usually sufficient to increase vaccine uptake. Education about the flu and flu vaccines is most effective when complemented with easy access and making the vaccine free, although this combination may not be sufficient to achieve the desired vaccination levels among HCWs. The findings point toward adding incentives for HCWs to get vaccinated and requiring them to record their vaccination status on a declination/consent form – either written or electronic. ^ Based on these findings, American health care organizations, such as hospitals, nursing homes, and long-term care facilities, should consider using online declination forms as a method for increasing influenza vaccination rates among their employees. These online forms should be used in conjunction with other policies, including free vaccine, mobile distribution and incentives. ^ To further spur health care organizations to adopt policies and practices that will raise influenza vaccination rates among employees, The Joint Commission – an independent, not-for- profit organization that accredits and certifies more than 17,000 health care organizations and programs in the United States – should consider altering its standards. Currently, The Joint Commission does not require signed declination forms from employees who eschew vaccination; it only echoes the CDC's recommendations: "Health care facilities should require personnel who refuse vaccination to complete a declination form." Because participation in Joint Commission accreditation is required for Medicare reimbursement, action taken by the Joint Commission to require interventions such as mandatory declination/consent forms might result in immediate action by health care organizations to follow these new standards and lead to higher vaccination rates among HCWs.^ 1“Frequently Asked Questions for H1N1 and Seasonal Influenza.” The Joint Commission - Infection Control: http://www.jointcommission.org/PatientSafety/InfectionControl/h1n1_faq.htm. ^

Lessons learned from nationwide vaccine programs: Comparing human papillomavirus, poliomyelitis vaccine, and swine flu

This assessment compares the human papillomavirus (HPV) nationwide vaccine to the poliomyelitis vaccine and the swine flu vaccine with the purpose of finding parallels and lessons in the controversies faced by the development and use of the vaccines. There are a number of great barriers that are facing the HPV vaccine to date. These controversies lie in dealing with the risk involved in taking the vaccine, how much control the government should have in administering the vaccine, how to communicate the risk to the public, and the cost-effectiveness of the vaccine versus treatment for cervical cancer. The lessons for the HPV vaccine that were learned after comparison and assessment of the controversies were: (1) plan ahead of time on how to inform the public if a risk develops from taking the HPV vaccination and it may be better to provide some information while the event is occurring, always being as truthful as possible, and later dispensing more information once all of the facts are known, (2) the human papillomavirus is not something that will become a pandemic in a short amount of time because the virus takes a long time to develop into cervical cancer, so if a major risk begins to show after continuing to develop and administer the vaccine for an amount of time, it may be better to take it off the market for a while and possibly reconfigure it to help eliminate some of the risks, (3) if side reactions and risks do develop and the government assumes liability for these reactions, the cost-effectiveness can be greatly affected, so it is important to be constantly checking to see if all the monetary and health benefits of the vaccine are outweighing any of the negative costs of the vaccine, and lastly, (4) the public must feel that every aspect of the vaccine, both good and bad, has been thought over and the benefits of taking the vaccine prevail over the negatives and that politics and commercial interests have nothing to do with the production and administration of the vaccine. ^

Modeling the impact of potential vaccines on epidemics of sexually transmitted chlamydia trachomatis infection

Background. We investigated the likely impact of vaccines on the prevalence of and morbidity due to Chlamydia trachomatis (chlamydia) infections in heterosexual populations. Methods.An individual‐based mathematical model of chlamydia transmission was developed and linked to the infection course in chlamydia‐infected individuals. The model describes the impact of a vaccine through its effect on the chlamydial load required to infect susceptible individuals (the “critical load”), the load in infected individuals, and their subsequent infectiousness. The model was calibrated using behavioral, biological, and clinical data. Results.A fully protective chlamydia vaccine administered before sexual debut can theoretically eliminate chlamydia epidemics within 20 years. Partially effective vaccines can still greatly reduce the incidence of chlamydia infection. Vaccines should aim primarily to increase the critical load in susceptible individuals and secondarily to decrease the peak load and/or the duration of infection in vaccinated individuals who become infected. Vaccinating both sexes has a beneficial impact on chlamydia‐related morbidity, but targeting women is more effective than targeting men. Conclusions.Our findings can be used in laboratory settings to evaluate vaccine candidates in animal models, by regulatory bodies in the promotion of candidates for clinical trials, and by public health authorities in deciding on optimal intervention strategies.

Plant-produced vaccines: promise and reality

Plant-produced vaccines are a much-hyped development of the past two decades, whose time to embrace reality may have finally come. Vaccines have been developed against viral, bacterial, parasite and allergenic antigens, for humans and for animals; a wide variety of plants have been used for stable transgenic expression as well as for transient expression via Agrobacterium tumefaciens and plant viral vectors. A great many products have shown significant immunogenicity; several have shown efficacy in target animals or in animal models. The realised potential of plant-produced vaccines is discussed, together with future prospects for production and registration. © 2008 Elsevier Ltd. All rights reserved.

Plant-made vaccines for humans and animals

Summary: The concept of using plants to produce high-value pharmaceuticals such as vaccines is 20 years old this year and is only now on the brink of realisation as an established technology. The original reliance on transgenic plants has largely given way to transient expression; proofs of concept for human and animal vaccines and of efficacy for animal vaccines have been established; several plant-produced vaccines have been through Phase I clinical trials in humans and more are scheduled; regulatory requirements are more clear than ever, and more facilities exist for manufacture of clinic-grade materials. The original concept of cheap edible vaccines has given way to a realisation that formulated products are required, which may well be injectable. The technology has proven its worth as a means of cheap, easily scalable production of materials: it now needs to find its niche in competition with established technologies. The realised achievements in the field as well as promising new developments will be reviewed, such as rapid-response vaccines for emerging viruses with pandemic potential and bioterror agents. © 2010 The Author. Journal compilation © 2010 Blackwell Publishing Ltd.

Expression of HIV-1 antigens in plants as potential subunit vaccines

Background Human immunodeficiency virus type 1 (HIV-1) has infected more than 40 million people worldwide, mainly in sub-Saharan Africa. The high prevalence of HIV-1 subtype C in southern Africa necessitates the development of cheap, effective vaccines. One means of production is the use of plants, for which a number of different techniques have been successfully developed. HIV-1 Pr55Gag is a promising HIV-1 vaccine candidate: we compared the expression of this and a truncated Gag (p17/p24) and the p24 capsid subunit in Nicotiana spp. using transgenic plants and transient expression via Agrobacterium tumefaciens and recombinant tobamovirus vectors. We also investigated the influence of subcellular localisation of recombinant protein to the chloroplast and the endoplasmic reticulum (ER) on protein yield. We partially purified a selected vaccine candidate and tested its stimulation of a humoral and cellular immune response in mice. Results Both transient and transgenic expression of the HIV antigens were successful, although expression of Pr55Gag was low in all systems; however, the Agrobacterium-mediated transient expression of p24 and p17/p24 yielded best, to more than 1 mg p24/kg fresh weight. Chloroplast targeted protein levels were highest in transient and transgenic expression of p24 and p17/p24. The transiently-expressed p17/p24 was not immunogenic in mice as a homologous vaccine, but it significantly boosted a humoral and T cell immune response primed by a gag DNA vaccine, pTHGagC. Conclusion Transient agroinfiltration was best for expression of all of the recombinant proteins tested, and p24 and p17/p24 were expressed at much higher levels than Pr55Gag. Our results highlight the usefulness of plastid signal peptides in enhancing the production of recombinant proteins meant for use as vaccines. The p17/p24 protein effectively boosted T cell and humoral responses in mice primed by the DNA vaccine pTHGagC, showing that this plant-produced protein has potential for use as a vaccine.

A prime-boost immunisation regimen using recombinant BCG and Pr55 gag virus-like particle vaccines based on HIV type 1 subtype C successfully elicits Gag-specific responses in baboons

Mycobacterium bovis BCG is considered an attractive live bacterial vaccine vector. In this study, we investigated the immune response of baboons to a primary vaccination with recombinant BCG (rBCG) constructs expressing the gag gene from a South African HIV-1 subtype C isolate, and a boost with HIV-1 subtype C Pr55 gag virus-like particles (Gag VLPs). Using an interferon enzyme-linked immunospot assay, we show that although these rBCG induced only a weak or an undetectable HIV-1 Gag-specific response on their own, they efficiently primed for a Gag VLP boost, which strengthened and broadened the immune responses. These responses were predominantly CD8+ T cell-mediated and recognised similar epitopes as those targeted by humans with early HIV-1 subtype C infection. In addition, a Gag-specific humoral response was elicited. These data support the development of HIV-1 vaccines based on rBCG and Pr55 gag VLPs. © 2009 Elsevier Ltd. All rights reserved.

Third International Conference on plant-based vaccines and antibodies

This relatively new biennial meeting - the first was in Prague in 2005 - was chaired by Julian Ma (Guy's Hospital, London, UK), with Mario Pezzotti (University of Verona, Italy) as local organizer, and attracted approximately 180 delegates from 25 countries. The theme was 'Plant Expression Systems for Recombinant Pharmacologics': there were 46 talks gathered into two plenaries, 12 themed sessions and 72 posters. Topics covered included publicly funded and commercial developments, innovation, regulation and commercialization, competition with conventional technology, manufacture and new products. © 2009 Expert Reviews Ltd.

Human papillomavirus vaccines in plants

Human papillomaviruses are the etiological agents of cervical cancer, one of the two most prevalent cancers in women in developing countries. Currently available prophylactic vaccines are based on the L1 major capsid protein, which forms virus-like particles when expressed in yeast and insect cell lines. Despite their recognized efficacy, there are significant shortcomings: the vaccines are expensive, include only two oncogenic virus types, are delivered via intramuscular injection and require a cold chain. Plant expression systems may provide ways of overcoming some of these problems, in particular the expense. In this article, we report recent promising advances in the production of prophylactic and therapeutic vaccines against human papillomavirus by expression of the relevant antigens in plants, and discuss future prospects for the use of such vaccines. © 2010 Expert Reviews Ltd.

Swine flu, doctors and pandemics : Is there a duty to treat during a pandemic?

The swine influenza (H1N1) outbreak in 2009 highlighted the ethical and legal pressures facing general practitioners and health workers in emergency departments in determining the nature and limits of their obligations to their patients and the public. Health workers require guidance on the multiple, overlapping, and at times conflicting legal and ethical duties owed to patients and prospective patients, employers and fellow health workers, and their families. Existing sources of advice on these issues in Australia, by way of statements of medical ethics and other sources of advice, are shown to be in need of further amplification if health workers are to be provided with the certainty and guidance required. Given the complexity of the issues, Australia would therefore benefit from more extensive consultation with the variety of stakeholders involved in these questions if pandemic plans are to smoothly deal with future crises in an ethically and legally sound manner.