November 28-29, 2012
William H. Natcher Conference Center
U.S. National Institutes of Health
Bethesda, Maryland, USA
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View workshop plenary session presentations
Read article about the workshop in the January 2013 issue of the
NIEHS Environmental Factor newsletter
View final workshop agenda (November 19)
Pertussis, also known as whooping cough, is a highly contagious disease caused by the bacterium
Bordetella pertussis. Pertussis was one of the most common childhood diseases of the early
20th century and was once a major cause of childhood mortality in the United States. A whole-cell
vaccine introduced in the 1940s reduced the incidence of pertussis by more than 80%. Acellular
pertussis (aP) vaccines,
which became available in the 1980s, were developed in response to public concern with some common
side effects (e.g., fever, swelling at injection site) and rare serious events that coincided with
the use of whole-cell pertussis vaccines. These new generation aP vaccines contain different
combinations of the putative protective antigens of B. pertussis bacteria (e.g., inactivated
pertussis toxin [PTx/d], pertactin, and fimbriae) and are less reactogenic than whole-cell
Regulatory authorities require safety, potency, and purity testing prior to the release of each
production lot of pertussis or pertussis antigen-containing vaccines. The murine histamine sensitization
test (HIST) is a key safety test used to monitor residual levels of pertussis toxin in acellular
pertussis vaccines. This test is performed to ensure that pertussis toxin has been effectively
inactivated before release of vaccines. However, such testing may involve large numbers of mice,
some of which can experience significant unrelieved pain and distress. In addition, the HIST has
technical challenges requiring frequent retesting, thereby increasing vaccine testing expense and animal usage.
Download printable copy of workshop flyer
international workshop organized in 2010 by NICEATM, ICCVAM, and their international partners
identified the HIST as a priority for future research, development, and validation of alternative
test methods that could further reduce, refine (enhance animal well-being and lessen or avoid pain
and distress), or replace animal use for acellular pertussis vaccine safety testing.
Two international workshops held in June and August 2011 reviewed currently available alternative in vitro assays to
the HIST and discussed a path forward to achieve their validation and adoption.
The June 2011 workshop established the International Working Group on Alternatives to the HIST
to coordinate future studies on relevant alternative methods.
Participants at the August 2011 workshop further discussed and clarified regulatory agency requirements
to achieve the acceptance of alternative methods to the HIST and agreed that conducting a study using
spiked vaccines to compare the sensitivities of the HIST and in vitro assays would be important.
This workshop provided a forum to discuss and review the in vitro protocols and available data
from the International Working Group for Alternatives to HIST study and suggested future
collaborative projects using prepared materials. The workshop participants also reviewed additional new methods
and approaches for aP vaccine safety testing that should improve test accuracy, precision, and efficiency
while also reducing or replacing the use of animals in vaccine safety testing. Finally, the workshop participants discussed
the path toward global validation, acceptance, and implementation of scientifically valid
alternative methods for aP vaccines.
Federal Register notice announcing workshop
(77 FR 52333, August 29, 2012)
View Federal Register notice as webpage
Information About Related Lectures
Evaluation of Humane Endpoints for Pertussis Vaccine Safety Testing
November 27, 2012, 2:00-4:00 p.m. - William H. Natcher Conference Center
View flyer for lectures
Welcoming Remarks and Introduction
William Stokes, DVM, RADM, USPHS, NIEHS/NICEATM
Highly Sensitive Histamine-Sensitization Test for Residual Activity of Pertussis Toxin In Acellular Pertussis Vaccine Using Body Temperature Monitoring
Masaki Ochiai, PhD, National Institute of Infectious Diseases, Japan
In Search of a Humane Endpoint for the Histamine Sensitization Assay
Juan Arciniega, DSc, CBER, U.S. FDA
Note: At the speaker's request, this presentation is not available for public viewing and/or distribution. We apologize for the inconvenience.
News article: "
CDC: Whooping Cough Epidemic Worst in 50 Years
" — NBC News, July 19, 2012
The incidence of pertussis is on track to set a record high in the U.S. this year, according to
Dr. Anne Schuchat, director of the National Center for Immunization and Respiratory Diseases
at the Centers for Disease Control and Prevention. Of particular concern is an
outbreak in Washington state resulting in over 3,000 cases so far this year.
Dr. Schuchat, who is an Assistant Surgeon General, was keynote speaker at the 2010 ICCVAM
International Workshop on Alternative Methods to Reduce, Refine, and Replace the Use of Animals in Vaccine Potency and Safety Testing
News article: "Whooping Cough Vaccine Offered for Free" — Burlington (NC) Times-News, June 24, 2012
A sharp increase in the number of pertussis cases has prompted the North Carolina Department of Health and Human Services to
offer free vaccinations. Alamance County in central North Carolina has recorded 122 cases of pertussis since last December, as
compared to 126 cases statewide in all of 2011.