Smallpox Vaccine Stockpile and Vaccination Policy

Report for Congress
Smallpox Vaccine Stockpile
and Vaccination Policy
January 9, 2003
Judith A. Johnson
Specialist in Life Sciences
Domestic Social Policy Division

Congressional Research Service ˜ The Library of Congress

Smallpox Vaccine Stockpile and Vaccination Policy
Summary
On December 13, 2002, President George W. Bush announced the
administration’s long-awaited policy for vaccinating U.S. citizens against smallpox.
That same day, the government began vaccinating an estimated 500,000 troops and
other personnel who serve in high risk parts of the world. Voluntary vaccination of
up to 500,000 civilian healthcare and public health workers probably would not begin
until after January 24, 2003, a date set by Section 4 of the Homeland Security Act of
2002 (P.L. 107-296). The Bush Administration plan for civilian healthcare workers
follows the October 17, 2002, recommendations made by an advisory panel to the
Centers for Disease Control and Prevention (CDC) on several smallpox vaccination
implementation issues. The panel advised immunizing two groups of civilians: (1)
public health response teams who would investigate initial smallpox cases and
implement control measures; and (2) healthcare teams composed of 50-100
individuals at each of the 5,100 acute care hospitals in the United States who would
care for smallpox patients.
Smallpox vaccine has a higher rate of serious complications than any other
vaccine in current use. When this vaccine was routinely given more than 30 years
ago, about 1,000 persons per million vaccinated for the first time experienced
reactions that were serious but not life threatening, such as accidental inoculation, in
which the rash occurs elsewhere on the body (from the vaccination site) due to direct
contact with vaccinia. Blindness may result if the rash develops near the eye. About
14 to 52 people per million vaccinated for the first time developed potentially life
threatening reactions; one or two per million died as a result of vaccination. These
more serious complications include: (1) encephalitis which may be fatal or leave
survivors with paralysis or other central nervous system symptoms; (2) growth of the
vaccination lesion without healing, which occurs in immunocompromised individuals
and is often fatal; (3) passage of vaccinia to a fetus, which may lead to stillbirth; and
(4) development of vaccinial lesions over sites where there is or has been eczema,
which may be fatal. Because live vaccinia virus is used in the smallpox vaccine,
complications may occur in individuals who don’t even receive the vaccine but are
only exposed to someone who has recently been vaccinated. The federal government
is encouraging both academic scientists and companies to develop a safer vaccine
and antiviral treatments.
In the Homeland Security Act of 2002 (P.L. 107-296), Congress addresses the
smallpox vaccine liability concerns of vaccine manufacturers and health care workers
by designating them to be federal employees for the purpose of administering
smallpox vaccine. The federal government would assume liability for smallpox
vaccine-related injuries and deaths under the Federal Tort Claims Act which does not
permit jury trials or punitive damages. If an individual injured by the smallpox
vaccine were to file suit against the federal government, that individual would be
required to provide evidence of negligence. However, most vaccine-related injuries
are not the result of negligence. It is expected that health care insurance and worker’s
compensation programs would pay for patient care expenses in the event of a
smallpox vaccine-related injury. This report will be updated as needed.

Contents
Smallpox disease and smallpox vaccination.........................1
U.S. smallpox vaccination policy.................................3
Bush Administration policy..................................3
Events leading up to Bush Administration policy.................4
Control of a smallpox outbreak...................................6
U.S. stockpile of smallpox vaccine................................8
Wyeth Laboratories........................................8
Acambis .................................................9
Aventis Pasteur..........................................10
Development of new smallpox vaccines and treatments...............11
Legislation ..................................................12

Smallpox Vaccine Stockpile
and Vaccination Policy
The terrorist attacks of the fall of 2001 resulted in increased attention to
preparedness for other such possible events, one being the deliberate release of
variola virus, the virus which causes smallpox. Although there is little uneasiness
over the safety of the only known samples of variola virus, held by the CDC in
Atlanta and a laboratory near Novosibirsk in Russia, there is some concern that
samples of the virus may have been acquired by terrorists or rogue governments,
particularly because of the unrest that occurred during the break up of the Soviet
Union.¹
Smallpox disease and smallpox vaccination
Smallpox is transmitted via person-to-person contact or inhalation of saliva
droplets from the breath of an infected person. The incubation period of 12-14 days
(range 7-17 days) is followed by the sudden onset of flu-like symptoms. After 2-3
days the distinctive rash begins to appear, and it is this stage, which lasts for 7-10
days, that is most infectious. As scabs begin to form infectivity rapidly declines.
About 65% to 80% of survivors have deep scars or pockmarks which tend to occur
on the face. The last recorded natural case of smallpox occurred in Somalia in 1977;
a fatal laboratory-acquired case occurred in England in 1978. The last U.S. case was
in 1949. After a worldwide effort of organized vaccination, smallpox was declared
eradicated by the World Health Assembly in May 1980.
Smallpox vaccination is achieved via inoculation using live vaccinia virus, a
pox virus that is closely related to variola virus. Vaccination is highly effective: 95%
of people who receive the vaccine before exposure to smallpox (variola) virus will
be protected from developing the disease. Vaccination within 2 to 3 days after
exposure to variola will prevent smallpox or significantly lessen the effects of the
disease in most people. Vaccination 4 to 7 days after exposure to variola virus may
offer some protection from disease or may modify the severity of disease. A
successful vaccination provides 3 to 5 years of protection from smallpox. Partial
protection is thought to continue for 10 or more years but the length of time and level
of protection is uncertain.
Rather than the typical hypodermic needle, smallpox vaccine is given using a

2-pronged (bifurcated) needle that is dipped into the vaccine solution. The prongs

¹ See also: CRS Report RL31059, Biological Weapons: A Primer; RL31368; CRS Report
RL31368, Preventing Proliferation of Biological Weapons: U.S. Assistance to Former
Soviet States; and CRS Report RS21288, Smallpox: Technical Background on the Disease
and its Potential Role in Terrorism.

retain a drop of vaccine and the needle is jabbed into the upper arm several times
causing a drop of blood to form. Within 3 to 4 days an itchy bump develops; by the
end of a week a pus-filled blister forms and begins to drain. Because live vaccinia
virus is used in smallpox vaccine, care must be taken (hand washing, careful bandage
disposal) not to spread the virus to other parts of the body or to other people who may
be at risk for adverse reaction. During the second week, the blister drys and a scab
develops; the scab falls off in the third week, leaving a small scar. A successful
reaction, often referred to as a “take,” is often more evident in people who are
vaccinated for the first time than in those who are revaccinated.
The side effects associated with use of smallpox vaccine are not insignificant.
Less serious complications of vaccination include sore arm, headache, body ache,
fatigue, rash, and fever. When this vaccine was routinely given more than 30 years
ago, about 1,000 persons per million vaccinated for the first time experienced
reactions that were serious but not life threatening, such as accidental inoculation, in
which the rash occurs elsewhere on the body (from the vaccination site) due to direct
contact with vaccinia. Blindness may result if the rash develops near the eye. About
14 to 52 people per million vaccinated for the first time developed potentially life
threatening reactions; 1 or 2 per million died as a result of vaccination. These more
serious complications include:
^!postvaccinial encephalitis, which may be fatal or leave survivors
with paralysis or other central nervous system symptoms;
^!progressive vaccinia, or growth of the vaccination lesion without
healing, which occurs in immunocompromised individuals and is
often fatal;
^!fetal vaccinia, passage of vaccinia to a fetus, which may lead to
stillbirth;
^!eczema vaccinatum, or development of vaccinial lesions over sites
where there is or has been eczema, which may be fatal.
Because of the serious complications from the vaccine, and since the risk of
importation of a smallpox case had been greatly reduced due to vaccination programs
and quarantine regulation, the U.S. Public Health Service recommended in 1971 that
routine smallpox vaccination be discontinued; the U.S. program stopped in 1972.
Smallpox vaccination has not been required for international travel since January
1982 and distribution of the vaccine to the general public stopped in 1983. Routine
smallpox vaccination of U.S. health care workers was discontinued in 1976; military
recruits stopped receiving the vaccine in 1990.
An unfortunate side effect of the eradication of smallpox, widely acclaimed as
a major public health triumph, is that the U.S. population and the rest of the world
are vulnerable to biologic weapon attack using variola virus. In past natural
outbreaks, smallpox killed 30% of those who had no immunity. Approximately 119
million U.S. residents born after 1972 lack immunity. The immunity of the 157
million U.S. residents born before 1972 has declined and their level of disease
protection is uncertain.

U.S. smallpox vaccination policy
Bush Administration policy. On December 13, 2002, President George W.
Bush announced the administration’s long-awaited policy for vaccinating U.S.
citizens against smallpox.² That same day, the government began vaccinating an
estimated 500,000 troops and other personnel who serve in or may be sent to high
risk parts of the world and who are not medically at high risk of vaccine-related
adverse effects. The State Department will also offer the vaccine on a voluntary
basis to some overseas personnel.
Under the Bush Administration plan, civilian healthcare and public health³
workers will also be vaccinated against smallpox, but on a voluntary basis. The plan
for civilian healthcare workers follows the October 17, 2002, recommendations made
by an advisory panel to the Centers for Disease Control and Prevention (CDC) on
several smallpox vaccination implementation issues.⁴ The panel advised immunizing
two groups of civilians: (1) public health response teams who would investigate
initial smallpox cases and implement control measures; and, (2) healthcare teams
composed of 50-100 individuals at each of the 5,100 acute care hospitals in the
United States that would care for smallpox patients. Each volunteer will be
questioned about his or her medical history and educated on the medical risks
associated with the vaccine. If there is any indication that the individual may be at
risk for complications from the vaccine he or she would be directed to undergo
additional medical tests (HIV, pregnancy) before being vaccinated.
On November 22, 2002, CDC asked all 50 states, four cities (New York, Los
Angeles, Chicago, Washington, D.C.) and the territories to submit by December 9,
2002, a plan for immunizing the above-mentioned healthcare workers and public
health smallpox response teams. The plan should provide for immunization of the
teams within a 30-day time frame. CDC will review the plans and notify the state or
territory whether the plan was complete and met CDC criteria. Smallpox vaccine
will not be released until plans are approved by CDC. As of December 19, 2002,
CDC had received plans from all 50 states and Los Angeles, Chicago, New York City
and Washington D.C. According to CDC, the plans indicate that about 440,000

² Remarks by President Bush on December 13, 2002, regarding smallpox vaccination can
be found at: [http://www.whitehouse.gov/news/releases/2002/12/20021213-7.html]. See
also the White House fact sheet “Protecting Americans: Smallpox Vaccination Program”
at: [http://www.whitehouse.gov/news/releases/2002/12/20021213-1.html].
³ Because of liability concerns, vaccination of healthcare workers probably will not begin
until after January 24, 2003, a date effectively set by Section 4 of H.R. 5005, The Homeland
Security Act of 2002 (P.L. 107-296). In addition, Section 304 provides that the United States
may be held liable for injuries caused by a smallpox vaccine only if the vaccine was
administered during the effective period of a declaration of a public health emergency by
the Secretary of Homeland Security.
⁴ The October 17, 2002, ACIP Smallpox Vaccination Recommendations can be found at:
[http://www.bt.cdc.gov/age nt/sma llpox/ vaccination/acip-r ecs-oct2002.asp].

healthcare workers may be offered smallpox vaccine and over 3,600 medical
facilities that may participate are identified.⁵
Because of the health risk associated with the vaccine, President Bush stated
that as commander in chief he also would be vaccinated because he would not ask
others to take the risk unless he was willing to do the same. The president reportedly
received a smallpox vaccination on December 21, 2002, and has not experienced any
side effects.⁶ At the present time, however, smallpox vaccine is not recommended
for anyone else in the administration or the general public. The Department of
Health and Human Services (HHS)is working to develop a process to make smallpox
vaccine available to adults in the general public who insist on being vaccinated and
who are not at high risk for any of the complications posed by the vaccine. Such
individuals may be eligible to enroll in a clinical trial or may receive unlicensed
vaccine in 2003 or licensed vaccine in 2004.⁷ As of January 8, 2003, 5 clinical trials
of smallpox vaccine were recruiting patients.⁸
Events leading up to Bush Administration policy. Federal vaccination
policy attempts to balance the likelihood of the adverse effects of smallpox vaccine
against the likelihood of a biowarfare attack using variola virus. After the terrorist
attacks in the fall of 2001, CDC and HHS asked the Advisory Committee on
Immunization Practices (ACIP) to consider if changes were needed in the June 2001
recommendations on smallpox vaccination.⁹ Under the June 2001 recommendations,
only laboratory workers who directly handle smallpox-related virus were vaccinated.
Following public meetings, draft supplemental recommendations on smallpox
vaccination were developed by ACIP and the National Vaccine Advisory Committee
(NVAC). The draft was approved by ACIP on June 20, 2002.
Under the June 20, 2002, draft ACIP plan, vaccination of the general public
prior to a smallpox attack was not recommended because “the risk of an attack was
assessed to be low” and, therefore, “the potential benefits of vaccination do not
outweigh the risks of vaccine complications.” Instead ACIP recommended voluntary

⁵ CDC Telebriefing Transcript. Updates: Smallpox Educational Activities and West Nile
Virus. December 19, 2002. [http://www.cdc.gov/od/oc/media/transcripts/t021219.htm]
⁶ Allen, M. Bush Receives Smallpox Vaccination. Washington Post, December 22, 2002,
p. A11; Associated Press. Bush Fine After Vaccine, Washington Post, December 23, 2002,
p. A5; and, Associated Press. Bush Has No Ill Effects From Smallpox Vaccine, Washington
Post, January 7, 2003, p. A6.
⁷ See the White House fact sheet “Protecting Americans: Smallpox Vaccination Program”
at: [http://www.whitehouse.gov/news/releases/2002/12/20021213-1.html], and the White
House “Frequently Asked Questions” document at:
[ ht t p: / / www.whi t e house.gov/ news/ r el eases/ 2002/ 12/ 20021213-3.ht ml ] .
⁸ Further information on the smallpox vaccine clinical trials can be found at:
[ h t t p : / / www.c l i n i c a l t r i a l s .gov] .
⁹ ACIP is a 15 member group of medical and public health experts that provides advice to
CDC and the rest of HHS on vaccine use and policy for effective disease control in the
civilian population. ACIP recommendations can be found at:
[http://www.bt.cdc.gov/agent/smallpox/vaccination/index.asp].

smallpox vaccination of two groups. The first group would investigate initial
smallpox cases and implement control measures. The second group would consist
of healthcare personnel at a limited number of designated hospitals that would be
involved in caring for smallpox patients. ACIP estimated that under the June 2002
plan, 10,000 to 20,000 individuals would have received the vaccine. State health
officials and hospital administrators expressed concern over designating only certain
hospitals for the care of smallpox patients, reasoning that victims would likely go to
their nearest hospital.
The ACIP draft recommendations were reviewed by CDC and HHS and a
revised plan was sent in early September 2002 to the White House for approval. At
an October 4, 2002, news conference federal health officials stated they were
considering plans to immunize up to 10 million healthcare workers against smallpox
and offer the vaccine to the general public by 2004.¹⁰ In response to these statements,
the American Academy of Pediatrics (AAP) and the American Medical Association
(AMA) urged caution in expanding voluntary smallpox vaccination beyond front-line
healthcare workers citing as concerns the potential health risks of the vaccine, the
associated liability problems, and the public’s lack of knowledge about dangers of
the smallpox vaccine.¹¹ The American Academy of Family Physicians had
previously expressed a similar position.¹² The Infectious Disease Society of America
has also recommended that smallpox vaccination of the general public should not be
employed, not even on a voluntary basis.¹³
On October 17, 2002, ACIP released further recommendations on smallpox
vaccination. The recommendations were developed at the request of CDC with input
from NVAC and the Healthcare Infection Control Practices Advisory Committee
(HICPAC). The expert groups were asked to provide guidance on 8 smallpox
vaccination implementation issues. In response to concerns over the June 2002 plan
which designated only certain hospitals for the care of smallpox patients, the panel
advised voluntary immunization of health care teams (composed of 50-100
individuals) at each of the 5,100 acute care hospitals in the United States. ACIP
estimated that about 500,000 hospital workers would receive the smallpox vaccine
under the revised plan.
Some are hesitant to recommend vaccination of the general public prior to a
smallpox outbreak or attack because smallpox vaccine has a higher complication rate
than any other vaccine in current use. An estimated 28 million people with eczema
and 10 million people with a compromised immune system (for example, organ

¹⁰ Altman, L.K., and S.G. Stolberg. Smallpox Vaccine Backed for Public. New York Times,
October 5, 2002. p. A1, A12.
¹¹ The AAP statement can be found at:
[http://www.aap.org/advocacy/releases/octsmallpox.htm]. The AMA statement is at:
[ ht t p: / / www.ama-assn.or g/ ama/ pub/ pr i nt / a r t i c l e / 1617-6824.ht ml ] .
¹² The AAFP position can be found at: [http://www.aafp.org/x10636.xml?printxml].
¹³ The Infectious Disease Society of America (IDSA) is a professional society representing
7,000 physicians and scientists who specialize in infectious diseases. The IDSA website can
be found at: [http://www.idsociety.org/].

transplant recipients, HIV/AIDS or cancer patients) – approximately 15% of the
population – are at high risk for developing serious complications.¹⁴ Such
complications will also occur in the rest of the population, but at a lower rate.
Because live vaccinia virus is used in the smallpox vaccine, complications may
occur in individuals who don’t even receive the vaccine but are only exposed to
someone who has recently been vaccinated. One recent study found that even if high
risk individuals and their household contacts (25% of the U.S. population) were
excluded from vaccination, an estimated 1,600 serious adverse events and 190 deaths
would occur if people aged 1 to 29 years were vaccinated, and 4,600 serious adverse
events and 285 deaths would occur if people aged 1 to 65 years were vaccinated.¹⁵
Liability problems associated with the use of smallpox vaccine could be
enormous. Section 304 of the Homeland Security Act (P.L. 107-296) addresses
liability concerns of manufacturers and distributors of the smallpox vaccine,
healthcare entities where the smallpox vaccine is administered, and healthcare
workers who are authorized to administer the vaccine.¹⁶
Control of a smallpox outbreak
CDC has been updating the smallpox response plan that was previously
developed during the 1970s for responding to the potential importation of smallpox.
This document, called the CDC Smallpox Response Plan and Guidelines,
incorporates and extends many of the concepts and strategies that were successfully
used 30 to 40 years ago to control smallpox outbreaks and eradicate the disease.¹⁷
The CDC Plan, much of which has been in place for many years, assists state and
local public health departments in developing their own regionally tailored smallpox
outbreak response plans. It outlines the public health strategies and approaches that
would guide the response to a smallpox emergency and identifies many of the
federal, state and local activities that must be undertaken.
On September 23, 2002, the CDC released the “Smallpox Vaccination Clinic
Guide,” which provides operational and logistical considerations for mass voluntary
vaccinations in the event of a confirmed attack involving smallpox virus. The
“Clinic Guide” is a small part of the much larger CDC Smallpox Response Plan and
Guidelines. CDC is also working with state and local public health departments to
improve preparedness for responding to other potential bioterrorist weapons.

¹⁴ Kemper, A.M., et al. Expected Adverse Events in a Mass Smallpox Vaccination
Campaign. Effective Clinical Practice, v. 5, March/April 2002. p. 84-90.
¹⁵ Ibid., p. 84.
¹⁶ For further information on Section 304 of P.L. 107-296 see: CRS Report RL31649,
Homeland Security Act of 2002: Tort Liability Provisions, by Henry Cohen; and, Smallpox
Questions and Answers: Section 304 of the Homeland Security Act on the CDC website at:
[http://www.bt.cdc.gov/age nt/sma llpox/ vaccination/section-304-qa.asp].
¹⁷ The CDC Smallpox Response Plan and Guidelines can be found at:
[http://http://www.bt.cdc.gov/agent/smallpox/response-plan/index.asp].

In the past, naturally occurring outbreaks of smallpox have been controlled
using ring vaccination: all the patient’s contacts are tracked down, vaccinated and
quarantined until the disease spread is stopped. Such a strategy is logical if there is
limited vaccine, or a significant level of smallpox immunity in the population, or if
a society wishes to limit the number of adverse events and fatalities caused by mass
smallpox vaccination. However, in a modern society with low levels of smallpox
immunity, mass transit and rapid forms of long distance travel, ring vaccination may
not be feasible especially if the attack occurs in many sites and infects a large number
of people at each site. Moreover, our social and economic system may be greatly
stressed by the necessary implementation of quarantine.¹⁸ Some experts also question
whether the existing public health system can actually implement a nation-wide
smallpox vaccination program quickly enough under a bioterrorist attack situation.¹⁹
Researchers are using mathematical models of disease transmission to determine
the outcome of a smallpox attack under a range of different conditions, such as the
number of initial infections, the transmission rate (number of secondary cases caused
by each initial case), the number of vaccinators, and whether ring or mass vaccination
is used to control the outbreak. The models are still under development and provide
contradictory results. For example, a model developed by researchers at Emory
University found that ring vaccination, even when it’s started only after the 25^th case
of smallpox, can contain an epidemic almost as well as mass vaccination, provided
that at least 80% of those exposed can be found and vaccinated.²⁰
In contrast, a model developed at Yale University found that mass vaccination
results in far fewer deaths and much faster epidemic eradication.²¹ The Yale model
predicts that in a smallpox attack on a large city causing 1,000 initial cases, ring
vaccination results in 367,000 cases and 110,000 deaths over 350 days, but mass
vaccination following an attack results in 1,830 cases and 560 deaths over 115 days.
However, if 40% of the population is vaccinated prior to attack, the number of deaths
would be reduced to 40,000 if ring vaccination is used following a 1,000-case attack,
but lowered even further to 440 deaths if mass vaccination is used after the attack.
The Yale group concludes that unless pre-attack vaccination is used, serious
consideration should be given to replacing the existing CDC policy with mass
vaccination in the event of a smallpox attack in a large urban center.
Traditional methods, like ring vaccination, are based on the fact that smallpox
spreads through person-to-person contact. A controversial report, presented at a June

15, 2002, Institute of Medicine meeting on smallpox vaccination, indicates that

¹⁸ For further information on quarantine issue see CRS Report RL31333, Federal and State
Responses to Biological Attacks: Isolation and Quarantine Authority, by Angie Welborn.
¹⁹ Foege, William. Can Smallpox Be As Simple As 1-2-3? Washington Post, December 29,

2002, p. B5.

²⁰ Enserink, M. How Devastating Would a Smallpox Attack Really Be? Science, v. 296,
May 31, 2002. p. 1592-1595.
²¹ Kaplan, E.H., et al. Emergency Response to a Smallpox Attack: the Case for Mass
Vaccination. Proceedings of the National Academy of Sciences, Early Edition, July 8, 2002.
[http://www.pnas.org]

aerosolized smallpox virus from a Soviet bioweapon test may have accidently caused

10 cases of smallpox and three deaths in 1971 in what is now Aralsk, Kazakhstan.²²

Some scientists criticized the report because they believe that aerosolized smallpox
virus would be quickly inactivated by environmental factors, such as UV radiation
from the sun. However, the authors of the report believe the best explanation for the
outbreak is that the initial case, a technician on a research vessel, acquired smallpox
when her boat entered waters 9 miles downwind from a Soviet bioweapons test site
located on Vozrozhdeniye Island in the Aral Sea. Because an aerosol of smallpox
virus would have the potential to infect a much larger number of people than person-
to-person contact, this report is of concern to public health experts.
Although the 119 million unvaccinated people in the U.S. could face a mortality
rate of about 30% in a smallpox attack, there is some question over the level of
protection remaining in the 157 million individuals who were vaccinated more than
30 years ago. Complete protection from smallpox disease begins to taper off 3 to 5
years after vaccination. However, some historical data indicate that vaccinated
individuals may experience milder disease symptoms and a lower mortality rate (5%
instead of 30%) even up to 50 years post-vaccination.²³ Additional studies would be
needed to confirm this point, but if correct, a smallpox attack might not be as deadly
or spread as rapidly as some experts had thought. It might also influence decisions
on who in the U.S. population should be the first to receive vaccines if a smallpox
attack does take place.
U.S. stockpile of smallpox vaccine
Within the last year, HHS has been successful in greatly increasing the U.S.
stockpile of smallpox vaccine via agreements with three separate sources: Wyeth
Laboratories, a pharmaceutical company located in Marietta, PA; Acambis, a British
drug firm with offices in Cambridge, MA; and Aventis Pasteur, a French vaccine
company with a plant in Swiftwater, PA. The policy debate by ACIP and others on
how many U.S. residents should be vaccinated has been made possible by HHS
efforts to increase the U.S. stockpile of smallpox vaccine.
Wyeth Laboratories. In the fall of 2001, the National Institutes of Health
(NIH) funded a study on whether the 15.4 million doses of smallpox vaccine in the
U.S. stockpile could be diluted without losing potency. The vaccine, called Dryvax,
was manufactured by Wyeth in 1982. Results of the study, released in April 2002,

²² The report, CNS Occasional Paper No. 9, The 1971 Smallpox Epidemic in Aralsk,
Kazakhstan, and the Soviet Biological Warfare Program, edited by J.B. Tucker and R.A.
Zilinskas, was published by the Center for Nonproliferation Studies of the Monterey
Institute of International Studies. The report and commentaries on the report are available
at: [http://cns.miis.edu/pubs/opapers/op9/index.htm]. See also: Enserink, M. Did
Bioweapons Test Cause a Deadly Smallpox Outbreak? Science, v. 296, June 21, 2002. p.
2116-2117; Broad, W.J. and J. Miller. Report Provides New Details of Soviet Smallpox
Accident, New York Times, June 15, 2002, p. A1, A15; and Brown, B. Soviets had ‘71
Smallpox Outbreak. Washington Post, June 16, 2002, p. A25.
²³ Cohen, J. Smallpox Vaccinations: How Much Protection Remains? Science, v. 294,
November 2, 2001. p. 985.

indicate that the Dryvax can be safely diluted by a factor of 5 or 10. In 97% to 99%
of study participants the diluted vaccine produced a “take” or skin lesion, a positive
indicator of a protective immune response.²⁴ Although none of the 680 study
subjects, aged 18 to 32, had a serious adverse reaction, there was a high frequency
of pain, swelling and redness at the inoculation site as well as fever, headache, rash,
muscle aches, fatigue and chills. More than a third of the subjects missed work,
school, sleep, or other activities because of an adverse reaction.
On October 25, 2002, the Food and Drug Administration (FDA) approved a
supplement to the license application for Dryvax. Although the original license for
Dryvax has been in effect since 1931, a supplemental approval was necessary
because a new liquid (diluent) is used to reconstitute the vaccine and a different
manufacturer is used to make the bifurcated needles.²⁵ Of the 15.4 million doses of
Dryvax held by HHS, only 2 lots – 2.7 million doses – have been released for use;
1 million doses will be set aside for the military and 1.7 will be for civilian use. The
license only applies to an undiluted vaccine. Individuals in the military and
healthcare workers who will be vaccinated under the initial stages of the Bush
Administration plan will be given full strength smallpox vaccine rather than a
diluted version. The remaining 12.7 million doses of Dryvax will be released on a
lot by lot basis. Availability of the diluted vaccine will be limited to clinical trial
settings.
Acambis. On November 28, 2001, HHS announced that Acambis Inc. had
been awarded a $428 million contract to produce an additional 155 million doses of
smallpox vaccine by the end of 2002; this amount expands on an initial order of 54
million doses.²⁶ In September 2000 CDC had awarded a contract to Acambis for 40
million doses of smallpox vaccine by 2004. In September 2001 CDC renegotiated
an accelerated production schedule under which Acambis agreed to produce 54
million doses by late 2002.
According to Acambis, the terms of the contracts with the federal government
limit its ability to provide much detail on the status, quality or timing of delivery of²⁷
smallpox vaccine. Acambis states this is for security reasons, because the vaccine
is intended to protect U.S. citizens from a potential bioterrorist attack. However,
Acambis indicated that significant progress has been made towards achieving the
contractual objectives. The first doses of smallpox vaccine have been produced for
the U.S. vaccine stockpile and, according to an Acambis news release, CDC is fully

²⁴ Frey, S.E. et al. Clinical Responses to Undiluted and Diluted Smallpox Vaccine. New
England Journal of Medicine, v. 346, April 25, 2002. p. 1265-1273.
²⁵ Wyeth Dryvax Smallpox Vaccine Approved for 100-Dose Kit, 30-Day Expiration. Pink
Sheet, November 11, 2002, p. 22; and Connolly, C. FDA Grants License for Smallpox
Vaccine. Washington Post, November 2, 2002, p. A13.
²⁶ The November 28, 2001, HHS press release can be found at:
[http://www.hhs.gov/news/ press/2001pres/20011128.html ].
²⁷ Interim results for the 6 months ended 30 June 2002. Acambis news release dated
September 18, 2002, found at: [http://www.acambis.com].

supportive of the progress made to date. CDC expects production of the Acambis
vaccine to be completed in May 2003.²⁸
The Acambis vaccine uses a single strain of vaccinia rather than the mixture
used in Dryvax. Also, the vaccinia virus used in the Acambis vaccine is produced
in cell culture in contrast to the traditional method used to make Dryvax in which
vaccinia virus was grown on the skin of live calves. Although animal studies
indicate that the Acambis version may have a lower risk of causing encephalitis, the
other side effects are expected to be about the same as the traditional vaccine.
Phase I clinical trials²⁹ comparing the Acambis vaccine with Dryvax began in
March 2002.³⁰ In September 2002 Acambis announced the results of the Phase I
trials and stated that the vaccine was well tolerated and caused an immune system
reaction in research subjects.³¹ All 100 previously unvaccinated subjects developed
a “take” within 10 days after vaccination with the Acambis vaccine; there were no
serious or unexpected adverse events. Acambis is currently conducting Phase II
clinical trials and expects to begin Phase III trials in 2003. The company indicates
that the work required to obtain FDA approval of the vaccine could continue through
early 2005.³²
Aventis Pasteur. At the end of March 2002, Aventis announced that it
sought to donate to the U.S. government about 85 million doses of smallpox vaccine
that were manufactured in 1958 for the U.S. Department of Defense. Preliminary
tests of the Aventis vaccine indicate that it is probably as potent as Dryvax.³³ Both
the Aventis vaccine and Dryvax were manufactured using traditional methods
involving live calves. Clinical trials of the Aventis vaccine began in the spring of

2002. Dilution tests of the vaccine will also be conducted.

Negotiations with the federal government for the donation began in October

2002. The company estimates the value of its donation at $150 million. However,

according to a company spokesman, prior to September 11, 2001, Aventis was “in

²⁸ CDC, personal communication, January 9, 2003.
²⁹ Most clinical trials are designated as Phase I, II, or III, based on the type of questions the
study is trying to answer. In Phase I clinical trials, researchers test a new drug for the first
time in a small group of 20-80 people to evaluate safety and identify side effects. In Phase
II clinical trials, a larger group (100-300) of people is used to test efficacy and further
evaluate safety. In Phase III studies, 1,000 to 3,000 people are given the drug to confirm
effectiveness, monitor side effects, and compare it to commonly used treatments. These
phases are defined by the FDA in the Code of Federal Regulations.
³⁰ Enserink, M. Smallpox Vaccines: New Cache Eases Shortage Worries. Science, v. 296,
April 5, 2002. p. 25, 27.
³¹ Interim results for the 6 months ended 30 June 2002. Acambis news release dated
September 18, 2002, found at: [http://www.acambis.com].
³² Ibid.
³³ Enserink, Smallpox Vaccines: New Cache Eases Shortage Worries, p. 25.

the process of developing protocols for disposing of [the vaccine].”³⁴ Because the
vaccine consists of a live virus and is infectious, disposal of the vaccine would have
required FDA approval as well as additional expense to the company. When HHS
indicated its possible interest in acquiring the vaccine, Aventis completed the
viability testing that it had begun earlier when the company planned to dispose of the
vaccine. Aventis is requesting reimbursement for testing and packaging expenses
and presumably will be able use the value of the donation as a tax deduction.³⁵
Development of new smallpox vaccines and treatments
In the summer of 2002, CDC was negotiating a contract to increase the U.S.
stockpile of intravenous vaccinia immune globulin (IV-VIG), a product used to treat
some, but not all, serious adverse reactions to smallpox vaccine.³⁶ CDC was seeking
to increase the stockpile by 30,000 doses, the amount needed if a mass U.S. smallpox
vaccination did not include pregnant women. If pregnant women were included, an
additional 40,600 doses would be needed. The product was expected to be available
in 2003.³⁷ CDC also has a similar product manufactured in 1994, intramuscular
vaccinia immune globulin (IM-VIG), that could be used to treat 600-800 adverse
events, the number expected when vaccinating 4 to 6 million people.³⁸
If a smallpox vaccine could be used without the high rate of serious
complications, the threat of a bioterrorism weapon using smallpox virus would be
reduced. The federal government is encouraging both academic scientists and
companies to develop a safer vaccine. Aventis Pasteur plans to begin testing a
smallpox vaccine using a greatly weakened strain of vaccinia called NYVAC.³⁹
A combination of the traditional vaccine Dryvax with a primer vaccine called
modified vaccinia Ankara (MVA) is also being studied. MVA is given several
months before Dryvax to diminish serious side effects in healthy and high risk
individuals. MVA was used in German studies in the 1970s and recent studies by
Bavarian Nordic of Copenhagen. However, because MVA was never tested where

³⁴ Dove, Alan and Karen Birmingham. Smallpox Vaccination Becomes a Social, Financial
and Political Issue. Nature Medicine, v. 8, no. 5, May 2002, p. 428.
³⁵ Ibid.
³⁶ Smallpox Vaccine Adverse Event Treatment Will Be Made Under CDC Contract. The
Pink Sheet, July 1, 2002. p. 17-18.
³⁷ However, the White House “Frequently Asked Questions” document indicates that as of
the end of December 2002, the United States “will have more than 2,700 treatment doses
of VIG (enough for predicted reactions with more than 27 million people.” The FAQ
document is available at:
[ ht t p: / / www.whi t e house.gov/ news/ r el eases/ 2002/ 12/ 20021213-3.ht ml ] .
³⁸ Smallpox Vaccine Adverse Event Treatment Will Be Made Under CDC Contract. The
Pink Sheet, July 1, 2002. p. 17-18; and, The CDC Smallpox Vaccination and Adverse
Events Training Module–Vaccinia Immune Globulin: Current VIG Information, at:
[http://www.bt.cdc.gov/training/sma llpoxvaccine/reactions/vig_current.html ]
³⁹ Enserink, M. In Search of a Kinder, Gentler Vaccine. Science, v. 296, May 31, 2002. p.

1594.

smallpox virus was actively causing disease (such as Afghanistan in the 1970s), and
MVA with Dryvax does not produce a typical smallpox vaccine scar, there are
concerns that it may not provide adequate disease protection.
A monkey model of smallpox, developed by CDC and the U.S. Army Medical
Research Institute of Infectious Diseases (USAMRIID), will be used to test the
efficacy of newly developed smallpox vaccines. FDA amended its new drug and
biological product regulations so that products intended to prevent serious or fatal
conditions may be approved for use based on effectiveness data from animal studies
when human efficacy studies are not ethical or feasible. The new regulations took
effect on June 30, 2002.⁴⁰ Human safety tests are still required for licensing.
In addition to work on improved vaccine products against smallpox, scientists
at CDC and USAMRIID are working on antiviral treatments for smallpox. One drug,
cidofovir, has demonstrated activity against variola virus in preliminary tests. In
2001, an Investigational New Drug (IND) application was filed with FDA for the
“use of cidofovir in both the treatment of acute smallpox infection and the
management of adverse events associated with vaccinia immunization.”⁴¹ A White
House “Frequently Asked Questions” document on smallpox states that by the end
of December 2002, the United States “will have more than 3,500 treatment doses of
cidofovir (enough for predicted reactions with 15 million people).”⁴² Other
compounds 25 to 150 times more active than cidofovir have been identified and are
under investigation.⁴³
Legislation
During the 107^th Congress, legislation involving smallpox primarily addressed
concerns over availability of the smallpox vaccine and liability concerns over the use
of the vaccine. The Public Health Security and Bioterrorism Preparedness and
Response Act of 2002 (P.L. 107-188), signed by the President on June 12, 2002,
directs the Secretary of HHS to ensure that there is enough smallpox vaccine in the
Strategic National Stockpile to meet health security needs and authorizes $509
million for FY2002 and such sums as may be necessary through FY2006 for this
purpose. An emergency supplemental appropriation (P.L. 107-117), signed by the
President on January 10, 2002, provided $512 million for the purchase of smallpox
vaccine by HHS.
P.L. 107-296 (H.R. 5005, H.R. 5710), the Homeland Security Act of 2002,
addresses liability concerns of vaccine manufacturers and healthcare workers by
designating them to be federal employees for the purpose of administering smallpox

⁴⁰ FDA News, May 30, 2002, available at:
[ h t t p : / / www.f d a.go v/ bbs/ t opi cs/ n ews/ 2002/ new00811.ht ml ] .
⁴¹ LeDuc, J.W., et al. Smallpox Research Activities: U.S. Interagency Collaboration, 2001.
Emerging Infectious Diseases, v. 8, July 2002. p. 743-745.
⁴² The White House “Frequently Asked Questions” document is available at:
[ ht t p: / / www.whi t e house.gov/ news/ r el eases/ 2002/ 12/ 20021213-3.ht ml ] .
⁴³ LeDuc, Smallpox Research Activities: U.S. Interagency Collaboration, 2001, p. 744.

vaccine. The federal government would assume liability for smallpox vaccine related
injuries and deaths under the Federal Tort Claims Act which does not permit jury
trials or punitive damages. If an individual injured by the smallpox vaccine were to
file suit against the federal government, that individual would be required to provide
evidence of negligence. However, most vaccine-related injuries are not the result of
negligence. While it is expected that health care insurance and worker’s
compensation would pay for patient care expenses in the event of a smallpox
vaccine-related injury, it is unclear how such expenses of the uninsured would be
handled. P.L. 107-296 also amends P.L. 107-188 by moving authority for the
stockpile to the Department of Homeland Security (DHS); HHS would continue to
manage the stockpile and determine its contents.