Vaccines: The Week in Review

28 June 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

PATH said that MenAfriVac, a vaccine developed through the

Meningitis Vaccine Project (MVP) to protect against life-threatening
meningococcal meningitis, received prequalification from the World
Health Organization. The action clears the way for phased introduction of
the vaccine in Africa later this year, PATH said. Dr. Christopher J. Elias,
president and CEO of PATH, commented, “Prequalification is a major
milestone for MenAfriVac and MVP. This partnership between PATH and WHO
is a stellar example of our mission and strategy at work. Through nine years
of collaboration with a range of partners, WHO and PATH have been able to
bring this vaccine from idea to reality, and we’re poised now to deliver it to
the people who need it most.” PATH described meningococcal meningitis as a
bacterial infection of the fluid surrounding the brain and spinal cord which is
highly contagious and kills about one in ten people who get it. Even with
treatment, as many as a quarter of survivors suffer permanent damage—
most commonly hearing loss, mental retardation, or epilepsy. The infection
causes repeated epidemics during the annual dry season in sub-Saharan
Africa—a region known as “the meningitis belt.”
Dr. F. Marc LaForce, director of the Meningitis Vaccine Project, said, “At 40
cents a dose, it is a moral imperative to introduce the vaccine in meningitis
belt countries, most of which are among the poorest countries in the world. It
is everybody's wish that the global health community and funding agencies
will come forward to help introduce the first affordable conjugate vaccine that
offers the hope to end 100 years of group A meningitis epidemics in Africa.”
MenAfriVac is produced by the Serum Institute of India Ltd. (SIIL), which
received marketing authorization for export and use of MenAfriVac in Africa
earlier this year.
http://www.path.org/news/an100623-menafrivac.php

The WHO continues to issue weekly updates and occasional briefing notes
on the H1N1 pandemic at
http://www.who.int/csr/disease/swineflu/en/index.html
Pandemic (H1N1) 2009 - update 106
Weekly update
25 June 2010 -- As of 20 June, worldwide more than 214 countries and
overseas territories or communities have reported laboratory confirmed
cases of pandemic influenza H1N1 2009, including over 18209 deaths.
Situation update:
Worldwide, overall pandemic and seasonal influenza activity remains low.
Active transmission of pandemic influenza virus persists in parts of the
tropics, particularly in the Caribbean, West Africa, and South and Southeast
Asia. Pandemic and seasonal influenza viruses have been detected only
sporadically during the early part of winter in the temperate regions of the
southern hemisphere. Global circulation of seasonal influenza virus type B
viruses has declined substantially and persists at low levels in parts of East
Asia, Central Africa, and Central America. During the past month, seasonal
influenza H3N2 viruses have been detected at low levels across parts of East
Africa and South America. More at:
http://www.who.int/csr/don/2010_06_25/en/index.html

The IFPMA released a statement on the overall response to the

2009-10 H1N1 influenza pandemic. IFPMA noted that “from the
perspective of the vaccine manufacturers, several elements of the
response were particularly effective:
- High level of preparedness. For many years prior to the H1N1
outbreak, public health authorities, regulatory agencies and vaccine
producers worked together on pandemic preparedness. These efforts
intensified following the spread of H5N1 ‘avian’ influenza. The resulting
level of preparedness allowed authorities to respond robustly to the
H1N1 pandemic, in a manner that was not previously possible.
- Global co-operation and flexibility. The rapid development and testing
of H1N1 vaccines presented many technical challenges, particularly in
the initial stages. WHO network and industry scientists worked
together, to share technical information and resolve urgent key issues,
such as improving vaccine virus production yields and vaccine
standardization. Industry interaction with the WHO regarding the H1N1
pandemic was focused on the development of H1N1 pandemic
vaccines and on improving vaccine availability, and did not extend to
pandemic alert status decision-making.
- Robust vaccine monitoring. By implementing existing surveillance
plans and sharing data publicly, authorities were able to confirm
rapidly the safety of H1N1 vaccines.
IFPMA also noted that “improvements to several areas of the
pandemic response could strengthen future preparedness.
- Technical improvements. Production yields from initial H1N1 vaccine
viruses were 1/3 to 1/2 of those achieved with seasonal strains.
Therefore, processes to rapidly evaluate multiple candidate vaccine
strains and to select those with the best growth potential could
improve yields and increase vaccine supply. Similarly, processes to
speed up reagent production and broadening the range of techniques
available for vaccine standardization would accelerate vaccine
availability.
- Establishing advance supply agreements. Large numbers of countries
initiated negotiations for vaccine supply after the emergence of H1N1
influenza. Establishing advance supply agreements beforehand could
avoid the need for complex discussions under intense time pressure
during a pandemic.
- Enhancing regulatory processes. International co-operation, mutual
recognition of existing regulatory approvals and reduction of
bureaucracy could all accelerate vaccine availability, while maintaining
robust safety standards.
- Strengthening public communications. Throughout the pandemic,
vaccination rates have remained low even in target risk groups (for
instance, coverage among healthcare workers reached just 37.1% in
the USA by mid-January 2010(1) while a study of healthcare workers in
Greece showed an acceptance rate of only 17% for pandemic
vaccination(2)). In some instances, views propagated by social media
may have eroded public confidence in the safety of H1N1 vaccines.
Authorities need to recognize the importance of new communication
channels to motivate the public to seek vaccination. It is important to
emphasize the public health value and safety of vaccination, as well as
the comprehensive system that is in place to evaluate and monitor
vaccine safety.
1) US Centers for Disease Control and Prevention. MMWR April 2, 2010;59(12):357-362.
(http://www.cdc.gov/mmwr/pdf/wk/mm5912.pdf).
2) Rachiotis G, Mouchtouri VA, Kremastinou J, Gourgoulianis K, Hadjichristodoulou C. Low acceptance of
vaccination against the 2009 pandemic influenza A(H1N1) among healthcare workers in Greece. Euro
Surveill. 2010;15(6): pii=19486. Available online: (http://www.eurosurveillance.org/ViewArticle.aspx?
ArticleId=19486)
http://www.ifpma.org/News/NewsReleaseDetail.aspx?nID=13803

The PhRMA (Pharmaceutical Research and Manufacturers of

America) issued a statement regarding clinical trials conducted
abroad:
“America’s biopharmaceutical research companies are proud to be among
the nation’s primary economic engines. Pharmaceutical research companies
lead the world in the search for new life-saving and life-enhancing
medications and, in 2009 alone, invested an estimated $65.3 billion to
discover and develop new medicines.
“While the number of experimental medicines in clinical testing today –
more than 2,900 medicines for nearly 4,600 different indications – represents
an all-time high, America’s biopharmaceutical research companies develop
drugs for a worldwide market and conduct clinical trials inside and outside
the U.S.
“It’s important to remember that the Food and Drug Administration (FDA)
has jurisdiction over clinical trials conducted in foreign countries for drugs
approved in the U.S. or being studied for approval in the U.S. The same strict
regulatory standards apply to foreign trials as trials conducted domestically.
Sponsors are typically in communication with the FDA throughout clinical
trials – no matter where they are conducted.
“Clinical trials occur globally because we have global companies that make
medicines for use around the world. Our member companies make every
effort to combat diseases that are common in the developed, as well as the
developing world. That can, ultimately, deliver life-saving and life-enhancing
medications to patients around the world more quickly.
“Is it ethical to conduct such studies outside of the U.S.? In a word: Yes.
Consistent with PhRMA’s Principles on Conduct of Clinical Trials and
Communication of Clinical Trial Results, our member companies are
committed to adhering to Good Clinical Practice guidelines around the world.
“In fact, PhRMA has conducted educational seminars and symposiums – at
times, in conjunction with the FDA – in other countries to educate potential
clinical trial principal investigators about Good Clinical Practices, ethics
oversight by outside review boards, and the need to maintain the highest
standards for data quality.
“Regardless of the location, however, companies seeking U.S. approval
must maintain the FDA’s high standards for conducting the trial. For instance,
any related trials conducted outside the U.S. must comply with FDA
requirements covering Good Clinical Practices, in addition to meeting the
requirements mandated in these important emerging markets.
“Clinical research is a critical element in the development of revolutionary
medicines that help patients live longer, healthier lives. Through carefully
controlled clinical studies, researchers thoroughly assess the safety and
efficacy of new drug candidates.
“America’s pharmaceutical research and biotechnology companies have a
long-standing commitment to help ensure physicians and other healthcare
providers receive meaningful information from these clinical trials.
“The PhRMA Clinical Trial Principles, created in 2002 and strengthened last
year, have been an invaluable guide to member companies and underscore
our commitment to the safety of clinical trial participants and communication
of important medical findings from clinical trials.”
http://www.phrma.org/news/news/phrma_statement_foreign_clinical_trials

The MMWR for June 25, 2010 / Vol. 59 / No. SS–7 includes: Malaria
Surveillance — United States, 2008
Abstract
The majority of malaria infections in the United States occur among persons
who have traveled to areas with ongoing malaria transmission. CDC received
reports of 1,298 cases of malaria with an onset of symptoms in 2008 among
patients in the United States, a decrease of 13.8% from the 1,505 cases
reported for 2007 (p<0.001). The first documented case of simian malaria,
Plasmodium knowlesi, was reported in a U.S. traveler. The highest estimated
relative case rates of malaria among travelers occurred among those
returning from countries in West Africa. In the majority of reported cases, U.S.
civilians who acquired malaria abroad had not adhered to a
chemoprophylaxis regimen that was appropriate for the country in which they
acquired the infection. Any person who has been to a malarious area and who
subsequently develops a fever or influenza-like symptoms should seek
medical care immediately and report their travel history to the clinician;
investigation should always include blood-film tests for malaria with results
available immediately. Malaria infections can be fatal if not diagnosed and
treated promptly.
http://www.cdc.gov/mmwr/preview/mmwrhtml/ss5907a1.htm?
s_cid=ss5907a1_w

WHO’s Department of Immunization, Vaccines and Biologicals

released a call for peer-reviewers for its publications in the vaccines
and/or immunization field/s.
http://www.who.int/immunization/documents/peer_review_publications/en/ind
ex.html

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

Clinical Infectious Diseases

15 July 2010 Volume 51, Number 2
http://www.journals.uchicago.edu/toc/cid/current
[Reviewed last week]
Emerging Infectious Diseases
Volume 16, Number 7–July 2010
http://www.cdc.gov/ncidod/EID/index.htm
[No relevant content]

Human Vaccines
Volume 6, Issue 6 June 2010
http://www.landesbioscience.com/journals/vaccines/toc/volume/6/issue/6/
[Reviewed earlier]

JAMA
Vol. 303 No. 24, pp. 2443-2544, June 23/30, 2010
http://jama.ama-assn.org/current.dtl
[No relevant content]

Journal of Infectious Diseases

15 July 2010 Volume 202, Number 2
http://www.journals.uchicago.edu/toc/jid/current
[Reviewed last week]

The Lancet
Jun 26, 2010 Volume 375 Number 9733 Pages 2193 - 2278
http://www.thelancet.com/journals/lancet/issue/current
[No relevant content]

The Lancet Infectious Disease

Jul 2010 Volume 10 Number 7 Pages 441 - 504
http://www.thelancet.com/journals/laninf/issue/current
[Reviewed last week]

Nature
Volume 465 Number 7301 pp985-1110 24 June 2010
http://www.nature.com/nature/current_issue.html
Nature | Editorial
A pandemic of hindsight?
We must learn lessons from the handling of the flu pandemic to improve
future research and public-health responses to emerging diseases, but
retrospective hindsight and recriminations are not the answer.
Late this week, the Council of Europe's parliamentary assembly, a 47-
member-state body that promotes democracy and human rights in
Strasbourg, France, is scheduled to vote on a resolution expressing alarm
over the World Health Organization's (WHO's) handling of the H1N1 influenza
pandemic.
 The council should think twice. In conversations with more than a dozen flu
researchers and public-health officials from Australia, the United States, the
United Kingdom and several other countries, Nature heard many objections
to the conclusions of the report on which the resolution is based. Angus
Nicoll, a senior influenza expert at the European Centre for Disease
Prevention and Control (ECDC) in Stockholm, says that in the ECDC's opinion:
“The conclusions of the report do not fit the facts as we see them, and as are
backed up by science.”
Certainly, the council's inquiry into the pandemic started off by taking a
strong angle, with a December 2009 parliamentary motion entitled 'Faked
pandemics — a threat for health'. The motion asserted that “to promote their
patented drugs and vaccines against flu, pharmaceutical companies have
influenced scientists and official agencies, responsible for public health
standards, to alarm governments worldwide”.
Similar ideas are reiterated in the inquiry's draft final report, which was
adopted on 4 June by the council's health committee, and which also contains
the resolution to be voted on this week (see http://go.nature.com/txThYG).
“Drug firms 'encouraged world health body to exaggerate swine flu threat',”
declared Britain's Daily Mail newspaper that day, in a typical headline.
It is this kind of response that the WHO's defenders find so potentially
damaging — not least because it can only encourage the conspiracy theories
that already swirl around the pandemic, and diminish public confidence in
health authorities. It is indeed vital that health authorities are transparent in
their dealings with industry. But the drug industry is a necessary partner in a
pandemic response, as the producer of antivirals and vaccines. It would have
been irresponsible to exclude top academic experts from the decision-making
just because of industrial competing interests, which do not necessarily
represent conflicts of interest. Critics also tend to forget that in spring 2009
the WHO and national officials were struggling with large scientific
uncertainties, and the possibility that millions of people would die if the
response was inadequate (a reality that the Council of Europe report does
acknowledge).
Paul Flynn, a UK Labour Member of Parliament and rapporteur of the
inquiry, says he could not fully address Nature's queries as to the accuracy of
the science of some statements in the report, given the short deadline, but
says he feels that these are minor and do not significantly alter its
conclusions. “I will, of course consider your comments, but our concerns
remain unchallenged,” he says, adding that he would have any errors
corrected in the final report. He questions the criticism of the report, saying
that he believes industry lobbyists are working to undermine it.
The resolution states that the council is “alarmed” about the WHO's, the
European Union's and national governments' handling of the pandemic,
arguing that some decisions taken led to “distortion of priorities of public
health services across Europe, waste of large sums of public money, and also
unjustified scares and fears about health risks faced by the European public
at large”. It also affirms its concern over possible “undue influence” on
decisions by the pharmaceutical industry. Some of its recommendations,
such as calls for greater transparency, and creating a public fund for research
and trials independent of industry, are sensible. But many researchers
dispute its highly critical analysis of the pandemic response, which is
expanded on in an accompanying 15-page explanatory memorandum.
That said, however, there are plenty of lessons to be learned from the
WHO's response to the pandemic. Fortunately, there is at least one
independent review that seems to be looking for those lessons in the right
way — slowly and impartially, and without indulging in 20/20 hindsight. The
29-member panel, chaired by Harvey Fineberg, the president of the US
Institute of Medicine, is due to deliver its findings at next year's World Health
Assembly. Meanwhile, several national investigations are also under way —
as the flu pandemic played out, it was largely national governments, at least
in the rich countries, not the WHO, that led the pandemic responses. And
they have plenty of their own lessons to learn.
http://www.nature.com/nature/journal/v465/n7301/full/465985a.html
Special Sponsored Section: Outlook: Chagas disease

New England Journal of Medicine

Volume 362 — June 24, 2010 — Number 25
http://content.nejm.org/current.shtml
Perspective
Focus on Research: The Bumpy Road to Polio Eradication
J. F. Modlin [Free full-text]
Original Articles
Fractional Doses of Inactivated Poliovirus Vaccine in Oman
A. J. Mohammed and Others [Free full-text]
ABSTRACT
Background We conducted a clinical trial of fractional doses of inactivated
poliovirus vaccine administered to infants in Oman, in order to evaluate
strategies for making the vaccine affordable for use in developing countries.
Methods We compared fractional doses of inactivated poliovirus vaccine
(0.1 ml, representing one fifth of a full dose) given intradermally with the use
of a needle-free jet injector device, with full doses of vaccine given
intramuscularly, with respect to immunogenicity and reactogenicity. Infants
were randomly assigned at birth to receive either a fractional dose or a full
dose of inactivated poliovirus vaccine at 2, 4, and 6 months. We also
administered a challenge dose of monovalent type 1 oral poliovirus vaccine
at 7 months and collected stool samples before and 7 days after
administration of the challenge dose.
Results A total of 400 infants were randomized, of whom 373 (93.2%)
fulfilled the study requirements. No significant baseline differences between
the groups were detected. Thirty days after completion of the three-dose
schedule, the rates of seroconversion to types 1, 2, and 3 poliovirus were
97.3%, 95.7%, and 97.9%, respectively, in the fractional-dose group, as
compared with 100% seroconversion to all serotypes in the full-dose group
(P=0.01 for the comparison with respect to type 2 poliovirus; results with
respect to types 1 and 3 poliovirus were not significant). The median titers
were significantly lower in the fractional-dose group than in the full-dose
group (P<0.001 for all three poliovirus serotypes). At 7 months, 74.8% of the
infants in the fractional-dose group and 63.1% of those in full-dose group
excreted type 1 poliovirus (P=0.03). Between birth and 7 months, 42
hospitalizations were reported, all related to infectious causes, anemia, or
falls, with no significant difference between vaccination groups.
Conclusions These data show that fractional doses of inactivated poliovirus
vaccine administered intradermally at 2, 4, and 6 months, as compared with
full doses of inactivated poliovirus vaccine given intramuscularly on the same
schedule, induce similar levels of seroconversion but significantly lower titers.
(Current Controlled Trials number, ISRCTN17418767 [controlled-trials.com] .)
Implications of a Circulating Vaccine-Derived Poliovirus in Nigeria
H. E. Jenkins and Others [Free full-text]
ABSTRACT
Background The largest recorded outbreak of a circulating vaccine-derived
poliovirus (cVDPV), detected in Nigeria, provides a unique opportunity to
analyze the pathogenicity of the virus, the clinical severity of the disease,
and the effectiveness of control measures for cVDPVs as compared with wild-
type poliovirus (WPV).
Methods We identified cases of acute flaccid paralysis associated with fecal
excretion of type 2 cVDPV, type 1 WPV, or type 3 WPV reported in Nigeria
through routine surveillance from January 1, 2005, through June 30, 2009.
The clinical characteristics of these cases, the clinical attack rates for each
virus, and the effectiveness of oral polio vaccines in preventing paralysis from
each virus were compared.
Results No significant differences were found in the clinical severity of
paralysis among the 278 cases of type 2 cVDPV, the 2323 cases of type 1
WPV, and the 1059 cases of type 3 WPV. The estimated average annual
clinical attack rates of type 1 WPV, type 2 cVDPV, and type 3 WPV per
100,000 susceptible children under 5 years of age were 6.8 (95% confidence
interval [CI], 5.9 to 7.7), 2.7 (95% CI, 1.9 to 3.6), and 4.0 (95% CI, 3.4 to 4.7),
respectively. The estimated effectiveness of trivalent oral polio vaccine
against paralysis from type 2 cVDPV was 38% (95% CI, 15 to 54%) per dose,
which was substantially higher than that against paralysis from type 1 WPV
(13%; 95% CI, 8 to 18%), or type 3 WPV (20%; 95% CI, 12 to 26%). The more
frequent use of serotype 1 and serotype 3 monovalent oral polio vaccines has
resulted in improvements in vaccine-induced population immunity against
these serotypes and in declines in immunity to type 2 cVDPV.
Conclusions The attack rate and severity of disease associated with the
recent cVDPV identified in Nigeria are similar to those associated with WPV.
International planning for the management of the risk of WPV, both before
and after eradication, must include scenarios in which equally virulent and
pathogenic cVDPVs could emerge.

The Pediatric Infectious Disease Journal

July 2010 - Volume 29 - Issue 7 pp: A5-A6,585-684
http://journals.lww.com/pidj/pages/currenttoc.aspx
[No relevant content]

Pediatrics
June 2010 / VOLUME 125 / ISSUE 6
http://pediatrics.aappublications.org/current.shtml
[Reviewed earlier]

PLoS Medicine
(Accessed 27 June 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
25 June 2010 Vol 328, Issue 5986, Pages 1599-1730
http://www.sciencemag.org/current.dtl
[No relevant content]

Science Translational Medicine

23 June 2010 vol 2, issue 37
http://stm.sciencemag.org/content/current
[No relevant content]

Vaccine
Volume 28, Issue 29, Pages 4539-4686 (23 June 2010)
http://www.sciencedirect.com/science/journal/0264410X
[Reviewed last week]