article on vaccines for BW with Nass comments

[Guest guest]

Others have already commented on this, but I wanted to put my 2 cents in

also. Dr. is a former Commander of USAMRIID at Fort Detrick, so

his words should closely reflect the views of DOD experts on the vaccine

rationale.

Meryl Nass

NOTE: To view the article with Web enhancements, go to:

http://www.medscape.com/govmt/CDC/EID/1999/v05.n04/e0504.11.russ/e0504.11.russ-0\

1.html.

Vaccines in Civilian Defense Against Bioterrorism

Philip K. , s Hopkins School of Public Health, Baltimore,

land, USA

[Emerging Infectious Diseases 5(4), 1999. Centers for Disease Control]

Introduction

In the United States, over the past half century, we have lived under

the protective umbrella of vaccination programs that

shield our population from a dozen serious and sometimes fatal naturally

transmitted illnesses. Vaccination has been the

single most cost-effective public health intervention. However, the

value of vaccines in protecting the population against the

deliberate release of infectious organisms is not so clear-cut.

The U.S. armed forces have recognized the military value of vaccines

against biological threats and have a long-standing

research and development program for a series of vaccines to protect

service members from hostile use of a biological agent.

Vaccination against anthrax is under way in all three armed services.

The Department of Defense has a large program to

develop and license additional vaccines for biological defense. For the

military, vaccination is an effective means of

countering a known threat because the population at risk is easily

defined and a high level of vaccine coverage can be

achieved.

DO I UNDERSTAND HIM CORRECTLY TO MEAN THAT MILITARY VACCINATION IS

EFFECTIVE FOR BW SIMPLY BECAUSE IT IS " DO-ABLE " IN THE MILITARY?

In evaluating the role of vaccines for protecting the civilian

population, quite different answers are reached. Despite the

protective efficacy of vaccines against individual organisms, the very

high costs and the great difficulties involved in

vaccinating large populations, along with the broad spectrum of

potential agents, make it impossible to use vaccines to

protect the general population against bioterrorism.

SINCE THE POTENTIAL AGENTS ARE THE SAME AS THE MILITARY MIGHT FACE, HE

SEEMS TO BE SAYING IT IS " IMPOSSIBLE " TO USE VACCINES SIMPLY BECAUSE

VACCINATING THE CIVILIAN POPULATION IS HARDER AND MORE EXPENSIVE.

Thus, vaccines cannot be considered a first line of defense against

bioterrorism for the general population, as they can be for the

relatively small military population. However, if *suitable*

vaccines

A BIG IF

can be made available, they have several potential uses: control of a

smallpox epidemic and prevention of a global

pandemic, postexposure prophylaxis against anthrax (with antibiotics),

and preexposure prophylaxis in first-responders at

high risk, laboratory workers, and health-care providers.

NOW HE SEEMS TO SAY THAT IF WE HAD A GOOD ANTHRAX VACCINE, THEN HE WOULD

WANT SELECTED CIVILIANS VACCINATED. THIS APPEARS TO BE AN ADMISSION

THAT THE CURRENT VACCINE IS UNSUITABLE.

Smallpox and anthrax, which pose the greatest risk for causing large

numbers of casualties in the event of an effective release

by a terrorist group, are at the top of the list of threat agents.

Licensed vaccines against both anthrax and smallpox that protect

against aerosol transmission are available.

THE GUINEA PIG AND MONKEY DATA DON'T PROVE THE CASE.

An existing licensed plague vaccine is protective against

flea-transmitted disease

but not against aerosol challenge in animal experiments or against

pneumonic plague.

THANK YOU FOR ADMITTING THIS. EVEN LAST DECEMBER, DOD WAS CLAIMING THEY

WISHED TO USE THE PLAGUE VACCINE FOR BW. I HAD TO POINT OUT IT WASN'T

EFFECTIVE WHEN REVIEWING THE MEDICAL LETTER DRAFT ON BW VACCINES.

This vaccine is in limited supply, and

the manufacturer has recently ceased production.

WISE MOVE, AVOIDS POTENTIALLY STICKY LIABILITY. THE MANUFACTURER ISN'T

PROTECTED FROM LIABILITY AS IS THE CASE FOR CHILDHOOD VACCINES.

The Department of Defense Joint Vaccine Acquisition Program has several

experimental vaccines in development (Table).

These vaccines will be further developed and tested with the intent of

obtaining products licensed by the U.S. Food and Drug

Administration.

Smallpox

One vaccine in development that is of great importance to civilian

biodefense is the vaccinia virus vaccine made in cell

culture. A new national stockpile of vaccinia vaccine is urgently needed

to respond to the possible threat of a deliberate

release of smallpox virus. Even though such release is unlikely, the

consequences of being unprepared would be a global

catastrophe. An unchecked epidemic in today's unvaccinated, densely

packed urban populations linked by rapid air travel

could kill millions. The only possible course of action would be to

mount a global effort to control the spread and eradicate

the disease using vaccinia virus vaccine. The number of deaths due to

secondary and subsequent spread of this highly

contagious virus would be determined by the rapidity of the public

health response, the effectiveness of a vaccination

campaign, and, most importantly, the availability of vaccine.

The national stockpile (fewer than 7 million doses of vaccinia virus

vaccine) is insufficient to meet national and international

needs in this scenario. The stockpile is also deteriorating

YES, THEY DO DETERIORATE, EVEN THOUGH DOD HAS A POLICY THAT VACCINES

LAST LONGTERM IN BULK STORAGE AND IN IND STATUS. THE WORLD'S LAST

SMALLPOX CASE OCCURRED OVER 20 YEARS AGO. HAS THE VACCINE BEEN TESTED

FOR DEGRADANTS?

and has a finite life span. The vaccine was made using the

traditional method of scarifying and infecting the flanks and bellies of

calves and harvesting the infected lymph. No

manufacturer exists today with the capability to manufacture calf lymph

vaccine by the traditional method. Replacing the

stockpile will require the development and licensure of a new vaccine

using modern cell-culture methods. This development

program, which will include process development, validation of a new

manufacturing process, and extensive clinical testing,

will be expensive and may take several years[1].

Obstacles to the development of the vaccine include the lack of

satisfactory stocks of vaccinia immune globulin necessary for

managing complications of vaccination. Clinical testing cannot proceed

without a supply of vaccinia immune globulin. As

part of the development effort, the problems associated with manufacture

of sufficient quantities of vaccinia immune globulin

will have to be addressed and solved. The Department of Defense program

is moving ahead with development of a

cell-culture vaccine by using a cloned strain of vaccinia derived from

another strain. Both civilian and military requirements

could be met by a combined and expanded development effort using either

the cloned strain or one of the licensed vaccinia

strains. The development costs will undoubtedly be high, as for any new

biologic product, but the cost of preparedness is

insignificant when weighed against the costs of an unchecked smallpox

epidemic.

Anthrax

Anthrax is the second threat that requires a major research and

development effort to meet civilian needs. A covert attack,

which exposes an urban population to an anthrax spore aerosol, is

thought by some to be the most likely scenario for a

bioterrorism attack. If the release is detected or the first cases are

rapidly diagnosed, rapid action can save many lives.

Providing the exposed population with antibiotics followed by

vaccination could be lifesaving for exposed persons who

would otherwise become ill with untreatable inhalation anthrax in the

subsequent few weeks.

THE ADMISSION: ANTIBIOTICS ARE LIFESAVING AFTER ANTHRAX EXPOSURE. BUT

YOU NEED TO START THEM SOON AFTER.

Prophylactic antibiotics alone

will prevent disease in persons exposed to antibiotic-susceptible

organisms, but incorporating vaccination into the treatment

regime can greatly reduce the length of treatment with antibiotics.

Without vaccination, antibiotics must be continued for 60

days; if effective vaccination can be provided, this can be reduced to

30 days.

PLEASE DON'T TELL ME WE ARE VACCINATING THE ENTIRE FORCE SIMPLY TO

SHORTEN THE PERIOD DURING WHICH ANTIBIOTICS ARE NEEDED. IS THE

RATIONALE FOR THIS VACCINE AS FLAWED AS THE RATIONALE OF PB FOR SARIN?

DOES DOD REALLY NOT HAVE A CLUE ABOUT THE SCIENTIFIC RATIONALE FOR THE

AVIP? WHO MADE THE DECISION TO BEGIN AND TO CONTINUE THE AVIP, AND DOES

THAT PERSON UNDERSTAND THE SCIENCE? WHO IS IT?

YES, YOU CAN MAKE ANTIBIOTIC RESISTANT STRAINS. YOU CAN MAKE VACCINE

RESISTANT STRAINS. BUT WE SEEM TO BE GOING ON FAITH THAT IT IS UNLIKELY

OUR TROOPS WILL FACE EITHER.

Vaccination of persons affected by an attack

will also face the issue of environmental contamination of urban areas

after an attack. Stockpiling a vaccine capable of

inducing protective immunity with two doses could be extremely valuable

in reducing the impact of a terrorist release of

anthrax.

The current anthrax vaccine manufactured by Bioport (formerly the

Michigan Department of Public Health Laboratory) is an

alum-adsorbed, partially purified culture filtrate of Bacillus anthracis

with a high protective antigen content. The schedule for

administration is 0, 2, and 4 weeks and 6, 12, and 18 months. This

vaccine is *safe and efficacious*

!!!

and is being used by the

armed forces to protect personnel against the use of anthrax as a

weapon. Immunization of rhesus monkeys followed by a

high-dose aerosol challenge has convincingly demonstrated the capability

of this vaccine to protect against aerosol challenge

with B. anthracis spores.

IN MONKEYS, USING THE AMES STRAIN ONLY

The multiple dose requirement, however, is a drawback for civilian use.

Studies in progress may find ways to allow modification of the schedule.

Vaccine supply is limited, as is production

capacity. As a result, at least for the immediate future, the armed

forces will require the entire available supply. This vaccine

is made by a method developed before the advent of molecular biology and

requires dedicated facilities because B. anthracis

is a spore-forming organism. In addition to having a multiple-dose

requirement, the vaccine is not highly purified and

contains multiple extraneous proteins. The characteristics of the

vaccine and the constraints on the present method of

manufacturing argue strongly against procuring large amounts for

civilian use

WHAT DOES HE MEAN BY CHARACTERISTICS OF THE VACCINE? IF IT'S SAFE AND

EFFECTIVE WHY NOT VACCINATE EVERYBODY?

when the technology and the science base exist

to rapidly develop a second-generation, improved anthrax vaccine.

Anthrax depends on two toxins (lethal factor and edema factor) for

virulence. A protein called protective factor is an essential

component of both toxins. The protective factor content is the basis for

the effectiveness of the current vaccine. A vaccine

based on purified protective factor made by recombinant technology has

been protective in animals[2]. Use of a *modern adjuvant*

THIS IS A CODE WORD FOR CURRENTLY UNLICENSED ADJUVANT; MOST OF THESE

STIMULATE THE IMMUNE SYSTEM EVEN MORE STRONGLY THAN ANTHRAX VACCINE AND

WOULD BE EXPECTED TO INDUCE GREATER AUTOIMMUNE ILLNESS

with purified recombinant protective factor should make it possible to

have a very effective two-dose vaccine. A

recent report of the Institute of Medicine Committee on Research and

Development to Improve Civilian Medical Response to

Chemical and Biological Terrorism makes a strong case for a major

research and development effort leading to an improved

second-generation vaccine[1].

Questions regarding the ability of existing anthrax vaccines to protect

against anthrax strains engineered to contain additional

virulence genes have been raised in Russia[3].

HE IS REFERRING TO THE ANTHRAX STRAIN ENGINEERED IN RUSSIA TO CONTAIN

CEREOLYSIN INSTEAD OF PA, AND BELIEVED TO BE VACCINE RESISTANT.

Research is needed to address this and related questions about the

pathogenesis of anthrax and protective immunity.

The value of vaccinating law-enforcement and emergency response

personnel, who must respond to threats (real or

otherwise), depends on the nature of their work and the immediacy of the

threat. Laboratory personnel who must work with

unknown materials and with high concentrations of known infectious

materials must be vaccinated.

WAIT A MINUTE. HOSPITAL MICROBIOLOGISTS WORK WITH DEADLY PATHOGENS

DAILY, UNDER A HOOD, WITH GLOVES AND MASK, AND ALMOST NEVER CONTRACT A

DISEASE THEY HAVE WORKED ON. UP TILL NOW, NO ONE SUGGESTED THEY RECEIVE

EXTRA VACCINATIONS.

These are additional

justifications for moving ahead with a vigorous development program for

anthrax and smallpox vaccines.

ARE WE GROPING FOR ADDITIONAL JUSTIFICATIONS HERE?

Dr. is professor, Center for Immunization Research, s

Hopkins School of Public Health; former Commander,

United States Army Medical Research and Development Command.

Address for correspondence: Philip K. , s Hopkins Center for

Civilian Biodefense Studies, Candler

Building, Suite 850, 111 Market Place, Baltimore, MD 21202, USA; fax:

410-223-1665; e-mail:biodefen@....

Table. Vaccines against biological agents

Licensed vaccines

Vaccines in research and development

Anthrax

Vaccinia (cell culture)

Smallpox (vaccinia)

Botulinum toxoids

Plague

Tularemia

 

Q fever

 

VEE EEE WEE

VEE, Venezuelan equine encephalitis; EEE, Eastern equine

encephalitis; WEE, Western equine encephalitis.

References

1.Committee on R & D Needs for Improving Civilian Medical Response to

Chemical and Biological Terrorism

Incidents. Institute of Medicine, National Academy of Sciences.

Chemical and Biological Terrorism. Research and

Development to Improve Civilian Medical Response. Washington:

National Academy Press; 1999.

2.Zajtchtchuk R, Bellamy RF, editors. Textbook of military medicine:

medical aspects of chemical and biological

warfare. Office of the Surgeon General, Department of the Army.

Washington, D.C.; 1997.

3.Pomeratnsev AP, Startsin NA, Mockov YV, Marnin LI. Expression of

cereolysin AB genes in Bacillus Anthracis

vaccine strain ensures protection against experimental hemolytic

anthrax infection. Vaccine 1997;15:1846-50.