Professional Documents
Culture Documents
13 September 2010
Center for Vaccine Ethics & Policy
http://centerforvaccineethicsandpolicy.wordpress.com/
A program of
- Center for Bioethics, University of Pennsylvania
http://www.bioethics.upenn.edu/
- The Wistar Institute Vaccine Center
http://www.wistar.org/vaccinecenter/default.html
- Children’s Hospital of Philadelphia, Vaccine Education Center
http://www.chop.edu/consumer/jsp/microsite/microsite.jsp
This weekly summary targets news and events in the global vaccines field gathered
from key governmental, NGO and company announcements, key journals and
events. This summary provides support for ongoing initiatives of the Center for
Vaccine Ethics & Policy, and is not intended to be exhaustive in its coverage.
Vaccines: The Week in Review is now also posted in a blog format at
http://centerforvaccineethicsandpolicy.wordpress.com/. Each item is treated as an individual
post on the blog, allowing for more effective retrospective searching. Given email
system conventions and formats, you may find this alternative more effective. This
blog also allows for RSS feeds, etc.
Comments and suggestions should be directed to
David R. Curry, MS
Editor and
Executive Director
Center for Vaccine Ethics & Policy
david.r.curry@centerforvaccineethicsandpolicy.org
Journal Watch
[Editor’s Note]
Vaccines: The Week in Review continues its weekly scanning of key journals
to identify and cite articles, commentary and editorials, books reviews and
other content supporting our focus on vaccine ethics and policy. Journal
Watch is not intended to be exhaustive, but indicative of themes and
issues the Center is actively tracking. We selectively provide full text of
some editorial and comment articles that are specifically relevant to our
work. Successful access to some of the links provided may require
subscription or other access arrangement unique to the publisher. Our initial
scan list includes the journals below. If you would like to suggest other titles,
please write to David Curry at
david.r.curry@centerforvaccineethicsandpolicy.org
Human Vaccines
Volume 6, Issue 9 September 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/9/
[Reviewed last week]
JAMA
Vol. 304 No. 10, pp. 1041-1140, September 8, 2010
http://jama.ama-assn.org/current.dtl
Commentaries
Public Reporting of Hospital Hand Hygiene Compliance—Helpful or
Harmful?
Matthew P. Muller; Allan S. Detsky
[First 150 words per JAMA convention; we include this commentary as it
relates to public reporting strategies associated with HCW influenza
immunization uptake]
Public reporting of hospital performance has been proposed as a means of
improving quality of care while ensuring both transparency and
accountability.1 Organizations feel pressure to perform well, deriving from
their desire to protect market share and defend reputations. This pressure, if
effectively harnessed, can lead to an increase in quality improvement
activities and better patient outcomes, although the evidence supporting the
latter claim is mixed.1
In 2002, it was estimated that approximately 1.7 million hospital-acquired
infections (HAIs) and 99 000 HAI-related deaths occurred in the United States
each year.2 Hand hygiene is considered the most important strategy to
prevent HAIs.3 Since 2002, an increasing number of US states have
mandated public reporting of quality indicators related to HAI prevention; to
date, none have included reports of hand hygiene compliance in their
mandates. This Commentary suggests the need for caution…
Do IRBs Protect Human Research Participants?
Christine Grady
[First 150 words per JAMA convention]
Institutional review boards (IRBs) are the core of the well-established US
system for the protection of human research participants. Institutional review
boards were initially created to provide independent review of research
conducted by researchers at their own institutions, impartial assessment of
the ethical acceptability of proposed research, and a check on investigators'
interests.1 Subsequently, advances in knowledge, technology, and resources
have changed the face of research. Pharmaceutical industry research
spending exceeds the National Institutes of Health (NIH) budget, which
increased from approximately $1 billion in 1970 to $30 billion in 2010.2
Multisite research, expansion into international and community settings,
novel scientific opportunities, freezers of stored samples, expanded
categories of researchers, and entities including contract research
organizations, data and safety monitoring committees, clinical trial
coordinating centers, and commercial IRBs have transformed the clinical
research enterprise.
Concurrently, the number of, investment in, and responsibilities of IRBs
have increased. . . .
Editorial
A Theme Issue on Infectious Disease and Immunology—Call for
Papers
Gianna Zuccotti; Phil B. Fontanarosa
[First 150 words per JAMA convention]
Infectious diseases and immunologic disorders are common reasons patients
seek medical care, can be associated with considerable morbidity, and
account for substantial health care expenditures. Each year, there are
millions of outpatient visits for a variety of infectious disorders, such as upper
respiratory tract infections, acute otitis media, skin infections, community-
acquired pneumonia, hepatitis, and sexually transmitted infections. In
addition, infectious processes may represent life-threatening conditions for
hospitalized patients, ranging from severe sepsis and ventilator-acquired
pneumonia to nosocomial infection with resistant organisms and surgical site
infections.
Despite control of some infectious processes, novel pathogens continue to
emerge and cause severe and widespread illness, such as pandemic 2009
influenza A(H1N1) and outbreaks with multidrug-resistant organisms. At the
same time, the pipeline for new antibiotics is limited since many
pharmaceutical companies have curtailed antimicrobial research and
development because of concerns about high costs, low . . .
The Lancet
Sep 11, 2010 Volume 376 Number 9744 Pages 845 - 928
http://www.thelancet.com/journals/lancet/issue/current
Editorial
Hepatitis E vaccine: why wait?
The Lancet
In The Lancet today, Buddha Basnyat asks why are hepatitis E and the
conjugate typhoid vaccines not available, despite their proven efficacy and
safety. In 2007, Mrigendra Prasad Shrestha and colleagues assessed the
safety and efficacy of a recombinant protein hepatitis E virus (HEV) vaccine
that was produced in insect cells by the US Army working with
GlaxoSmithKline. This vaccine showed 95·5% efficacy after administration of
three doses (20 μg per dose) at months 0, 1, and 6 in a phase 2 randomised
controlled trial of 2000 healthy, mostly young men in Nepal. Although
GlaxoSmithKline retains the intellectual property rights to this vaccine, it
reportedly has no plans for development. The results of Feng-Cai Zhu and
colleagues' phase 3 trial, reported in The Lancet today, using a recombinant
HEV vaccine (HEV 239), which was produced in bacterial cells, lend support to
the efficacy and safety of such a vaccine. HEV 239 was assessed in a general
population of healthy men and women (aged 16—65 years) living in Jiangsu
province, China. Three doses (30 μg of purified recombinant hepatitis E
antigen per dose) of HEV 239 administered at months 0, 1, and 6 resulted in
100% efficacy in 48 693 individuals, whereas 15 of 48 663 people given the
placebo (hepatitis B vaccine) developed hepatitis E.
HEV is a single-strand, positive-sense RNA virus that was first recognised in
India in the 1980s. This virus is transmitted enterically from individual to
individual through contaminated water and uncooked food, resulting in
hepatitis epidemics or sporadic cases. The highest incidence of sporadic
cases in developing countries is in the age group 15—35 years; in developed
countries, individuals older than 45 years have the highest incidence. A third
of the world's population, mostly in developing countries, is infected with
HEV. Genotypes 1, 2, and 4 are prevalent in developing countries, whereas
genotype 3 is prevalent in Europe and the USA. At least 50% of acute viral
hepatitis in endemic countries is caused by HEV. Because HEV infection is
self-limiting, the hepatitis is usually acute. Hepatitis E cannot be clinically
distinguished from the other acute viral hepatides; therefore, diagnosis is by
use of enzyme immunoassay for the detection of specific IgM or viral RNA
with reverse transcriptase polymerase chain reaction.
HEV vaccines should also be assessed in pregnant women (particularly those
in the second and third trimesters), immunosuppressed individuals, and
infants (<2 years). Efficacy and safety should first be assessed in pregnant
women with HEV infection, in whom fulminant hepatitis can arise. The
mortality rate is 5—25% in pregnant women compared with 1% in the
general population infected with the virus—eg, in one hospital in Kathmandu,
Nepal, 20—30% of pregnant women with hepatitis E die. HEV can be
vertically transmitted during pregnancy, and increases the risk of abortions,
stillbirths, deaths in newborn babies, and neonatal hypoglycaemia and liver
injury.
HEV infection in people with chronic liver disease can increase the mortality
rate—eg, 1-year mortality in Indian individuals with these comorbidities was
70%. Hence, individuals with underlying chronic hepatic disease might
benefit most from an HEV vaccine. The period of protection afforded with
vaccination against HEV should also be established.
Precautions for prevention of the spread of HEV include improvements in
sanitation, education about handwashing, and storage, handling, and
preparation of uncooked pork. Because no treatment exists for HEV infection,
development of a vaccine is the best way forward in developing and
developed countries. However, developing countries are unlikely to have the
resources needed to develop and test vaccines. So why have companies
invested their resources in creating vaccines such as those for HEV that are
safe and seem effective, and then not developed them when they are
urgently needed?
The answer might be that pharmaceutical companies do not think an HEV
vaccine is commercially viable. Hopefully, this situation will change after the
International Symposium on Hepatitis E in Seoul, South Korea, on Sept 15—
16. This symposium has been organised by the International Vaccine Institute
in collaboration with WHO. Experts from around the world will gather to share
data about hepatitis E epidemiology, disease burden, diagnostic methods,
and vaccines. One of the planned outcomes of this symposium is the
generation of strategies for the rapid development and delivery of HEV
vaccines, which is not a moment too soon.
Article
Efficacy and safety of a recombinant hepatitis E vaccine in healthy
adults: a large-scale, randomised, double-blind placebo-controlled,
phase 3 trial
Feng-Cai Zhu, Jun Zhang, Xue-Feng Zhang, Cheng Zhou, Zhong-Ze Wang,
Shou-Jie Huang, Hua Wang, Chang-Lin Yang, Han-Min Jiang, Jia-Ping Cai, Yi-Jun
Wang, Xing Ai, Yue-Mei Hu, Quan Tang, Xin Yao, Qiang Yan, Yang-Ling Xian,
Ting Wu, Yi-Min Li, Ji Miao, Mun-Hon Ng, James Wai-Kuo Shih, Ning-Shao Xia
Summary
Background
Seroprevalence data suggest that a third of the world's population has been
infected with the hepatitis E virus. Our aim was to assess efficacy and safety
of a recombinant hepatitis E vaccine, HEV 239 (Hecolin; Xiamen Innovax
Biotech, Xiamen, China) in a randomised, double-blind, placebo-controlled,
phase 3 trial.
Methods
Healthy adults aged 16—65 years in, Jiangsu Province, China were randomly
assigned in a 1:1 ratio to receive three doses of HEV 239 (30 μg of purified
recombinant hepatitis E antigen adsorbed to 0·8 mg aluminium hydroxide
suspended in 0·5 mL buffered saline) or placebo (hepatitis B vaccine) given
intramuscularly at 0, 1, and 6 months. Randomisation was done by computer-
generated permuted blocks and stratified by age and sex. Participants were
followed up for 19 months. The primary endpoint was prevention of hepatitis
E during 12 months from the 31st day after the third dose. Analysis was
based on participants who received all three doses per protocol. Study
participants, care givers, and investigators were all masked to group and
vaccine assignments. This trial is registered with ClinicalTrials.gov, number
NCT01014845.
Findings
11 165 of the trial participants were tested for hepatitis E virus IgG, of which
5285 (47%) were seropositive for hepatitis E virus. Participants were
randomly assigned to vaccine (n=56 302) or placebo (n=56 302). 48 693
(86%) participants in the vaccine group and 48 663 participants (86%) in the
placebo group received three vaccine doses and were included in the primary
efficacy analysis. During the 12 months after 30 days from receipt of the
third dose 15 per-protocol participants in the placebo group developed
hepatitis E compared with none in the vaccine group. Vaccine efficacy after
three doses was 100·0% (95% CI 72·1—100·0). Adverse effects attributable
to the vaccine were few and mild. No vaccination-related serious adverse
event was noted.
Interpretation
HEV 239 is well tolerated and effective in the prevention of hepatitis E in the
general population in China, including both men and women age 16—65
years.
Funding
Chinese National High-tech R&D Programme (863 programme), Chinese
National Key Technologies R&D Programme, Chinese National Science Fund
for Distinguished Young Scholars, Fujian Provincial Department of Sciences
and Technology, Xiamen Science and Technology Bureau, and Fujian
Provincial Science Fund for Distinguished Young Scholars.
Nature
Volume 467 Number 7312 pp133-244
http://www.nature.com/nature/current_issue.html
[No relevant content]
Nature Medicine
September 2010, Volume 16 No 9
http://www.nature.com/nm/index.html
News
Amidst growing vaccine concerns, NIH sets up engine for answers -
p940
Roxanne Palmer
Commentary
The 2010 scientific strategic plan of the Global HIV Vaccine
Enterprise
The Council of the Global HIV Vaccine Enterprise: Seth Berkley, Kenneth
Bertram,
Jean-François Delfraissy, Ruxandra Draghia-Akli, Anthony Fauci, Cynthia
Hallenbeck,
Madame Jeannette Kagame, Peter Kim, Daisy Mafubelu, Malegapuru W
Makgoba,
Peter Piot, Mark Walport, Mitchell Warren & Tadataka Yamada; for Members
of the Enterprise: José Esparza, Catherine Hankins, Margaret I Johnston, Yves
Lévy
& Manuel Romaris; for Alternate members: Rafi Ahmed & Alan Bernstein
[Selected excerpts from the full Commentary]
The 2010 Plan's two scientific priorities
Recognizing the importance of pursuing a diverse range of vaccine
concepts and approaches, the 2010 Plan prioritizes two main drivers key to
the next phase of HIV vaccine research and development that specifically
require global collaboration.
First, the Plan recognizes that clinical trials and human clinical investigation
present an unequalled opportunity to obtain important information about the
human immune system and its response to vaccine candidates and that they
are pivotal to advancing both vaccine discovery and vaccine development.
Human efficacy trials are essential to defining the ability of vaccines to
prevent infection or disease and for the discovery of vaccine-induced
correlates and signatures of protection, which would ultimately accelerate the
development or improvement of HIV vaccines for future licensure and public
health use. This scientific imperative—made possible by major advances in
laboratory and computational techniques that have opened up complex
biological systems, including the human immune system, to rigorous and
rapid scientific analysis—underpins the importance of clinical efficacy trials to
advancing vaccine discovery and development.
Second, the Plan recognizes that trials must be linked to and build upon the
tools and concepts of basic biomedical science, including genomics and
computational biology, immunology, virology and model systems, to optimize
both vaccine design and information on vaccine biology in humans. A
strengthened clinical trials effort must therefore be accompanied by
sustained, strong support for fundamental vaccine discovery research. In
pursuing an increasingly science-driven clinical trials effort, the field will
advance promising candidates toward vaccine licensure and, at the same
time, contribute fundamental scientific insights that will improve future
vaccine design, product development and clinical trials.
The 2010 Plan is therefore predicated on a multidisciplinary approach that
bridges the lab and the clinic, entrenching human research as intrinsic to the
discovery process, and mobilizing the collaborative efforts of basic, preclinical
and clinical scientists in highly iterative vaccine design and testing…
Conclusion and next steps
The creation of the Global HIV Vaccine Enterprise and its emphasis on a
shared Scientific Strategic Plan represents an unprecedented response by the
international scientific community to the scientific, public health and
humanitarian challenges posed by HIV/AIDS. Enterprise stakeholders have a
shared commitment to fulfill three essential functions: conducting regular
assessments of scientific priorities and updating them to reflect lessons
learned, new opportunities and the influence of new scientific findings and
new technologies, establishing global processes to address priority areas and
establishing a culture of mutual accountability for effective implementation of
the Plan by funders and investigators. These commitments remain imperative
to the fulfillment of the 2010 Plan in driving progress in the field.
Over the past 18 months, major scientific advances have signaled the
beginning of an important new phase in HIV vaccine research. At the same
time, there is increasing evidence that the epidemic is in danger of spinning
out of control. It is our collective responsibility to ensure that this moment is
not lost. Continued progress in the field urgently requires that funders, aid
agencies, researchers, industry, regulatory agencies, advocates and civil
society commit to working together as an open and collaborative global
community. Until a deployable, efficacious vaccine is developed, that
objective will be the only and ultimate goal of the Global HIV Vaccine
Enterprise.
Pediatrics
September 2010 / VOLUME 126 / ISSUE 3
http://pediatrics.aappublications.org/current.shtml
[Reviewed earlier]
PLoS Medicine
(Accessed 12 September 2010)
http://medicine.plosjournals.org/perlserv/?request=browse&issn=1549-
1676&method=pubdate&search_fulltext=1&order=online_date&row_start=1
&limit=10&document_count=1533&ct=1&SESSID=aac96924d41874935d8e1
c2a2501181c#results
[No relevant content]
Science
10 September 2010 Vol 329, Issue 5997, Pages 1241-1426
http://www.sciencemag.org/current.dtl
[No relevant content]
Science Translational Medicine
8 September 2010 vol 2, issue 48
http://stm.sciencemag.org/content/current
[No relevant content]
Vaccine
http://www.sciencedirect.com/science/journal/0264410