Impfen pro und Kontra: Neue Entwicklungen und Summary

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BMC Microbiol. 2006; 6: 16.
Published online 2006 February 24. doi: 10.1186/1471-2180-6-16.


Expression of hemagglutinin protein from the avian influenza virus H5N1 in a baculovirus/insect cell system significantly enhanced by suspension culture

Nitar Nwe,1 Qigai He,1 Sudarat Damrongwatanapokin,2 Qingyun Du,1 Ivanus Manopo,1 Yukol Limlamthong,2 Beau James Fenner,1 Lynn Spencer,1 and Jimmy Kwang1
1Animal Health Biotechnology Group, Temasek Life Science Laboratory, 1 Research Link, National University of Singapore, Singapore 117604, Singapore
2Department of Livestock Development, National Institute of Animal Health, Chatuchak, Bangkok, Thailand
Corresponding author.
Nitar Nwe: **********; Qigai He: **********; Sudarat Damrongwatanapokin: **********; Qingyun Du: **********; Ivanus Manopo: **********; Yukol Limlamthong: **********; Beau James Fenner: **********; Lynn Spencer: **********; Jimmy Kwang: **********
Received August 19, 2005; Accepted February 24, 2006.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.



Background
Prevention of a possible avian influenza pandemic necessitates the development of rapid diagnostic tests and the eventual production of a vaccine.


Results
For vaccine production, hemagglutinin (HA1) from avian influenza H5N1 was expressed from a recombinant baculovirus. Recombinant HA1 was expressed in monolayer or suspension culture insect cells by infection with the recombinant baculovirus. The yield of rHA1 from the suspension culture was 68 mg/l, compared to 6 mg/l from the monolayer culture. Immunization of guinea pigs with 50 μg of rHA1 yielded hemagglutinin inhibition and virus neutralization titers of 1:160 after two times vaccination with rHA1 protein.


Conclusion
Thus, the production of rHA1 using an insect suspension cell system provides a promising basis for economical production of a H5 antigen.
 
Nature. 2006 Aug 17;442(7104):757.
http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=Retrieve&db=PubMed&list_uids=16915278&dopt=AbstractPlus

Silent spread of H5N1 in vaccinated poultry.

Savill NJ, St Rose SG, Keeling MJ, Woolhouse ME.

Centre for Infectious Diseases, University of Edinburgh, Ashworth Laboratories, The King's Buildings, Edinburgh EH9 3JT, UK. **********

International debate on the merits of vaccinating poultry against the H5N1 influenza A virus has raised concerns about the possibility of an increased risk of between-flock transmission before outbreaks are detected. Here we show that this 'silent spread' can occur because of incomplete protection at the flock level, even if a vaccine is effective in individual birds. The use of unvaccinated sentinels can mitigate, although not completely eliminate, the problem.
 
1: Avian Dis. 2004 Jan-Mar;48 (1):167-76.

Comparative susceptibility of chickens and turkeys to avian influenza A H7N2 virus infection and protective efficacy of a commercial avian influenza H7N2 virus vaccine.

Tumpey TM, Kapczynski DR, Swayne DE.
Southeast Poultry Research Laboratory, United States Department of Agriculture, Agricultural Research Service, Athens, GA 30605, USA.

During the spring of 2002, a low pathogenic avian influenza (LPAI) A (H7N2) virus caused a major outbreak among commercial poultry in Virginia and adjacent states. The virus primarily affected turkey flocks, causing respiratory distress and decreased egg production. Experimentally, turkeys were more susceptible than chickens to H7N2 virus infection, with 50% bird infectious dose titers equal to 10(0.8) and 10(2.8-3.2), respectively. Comparison of virus shedding from the cloaca and oropharynx demonstrated that recent H7N2 virus isolates were readily isolated from the upper respiratory tract but rarely from the gastrointestinal tract. The outbreak of H7N2 virus raised concerns regarding the availability of vaccines that could be used for the prevention and control of this virus in poultry. We sought to determine if an existing commercial avian influenza (AI) vaccine prepared from a 1997 seed stock virus could provide protection against a 2002 LPAI H7N2 virus isolated from a turkey (A/turkey/Virginia/158512/02 [TV/02]) in Virginia that was from the same lineage as the vaccine virus. The inactivated AI vaccine, prepared from A/chicken/ Pennsylvania/21342/97 (CP/97) virus, significantly reduced viral shedding from vaccinated turkeys in comparison with sham controls but did not prevent infection. The protective effect of vaccination correlated with the level of virus-specific antibody because a second dose of vaccine increased antiviral serum immunoglobulin G and hemagglutination inhibition (HI) reactivity titers in two different turkey age groups. Serum from CP/97-vaccinated turkeys reacted equally well to CP/97 and TV/02 antigens by HI and enzyme-linked immunosorbent assay. These results demonstrate the potential benefit of using an antigenically related 1997 H7N2 virus as a vaccine candidate for protection in poultry against a H7N2 virus isolate from 2002.
 
Impfgegner, ein Problem das Geschichte hat

The Last Smallpox Epidemic in Boston and the Vaccination Controversy, 1901–1903

One hundred years ago, Boston had its last epidemic of smallpox. We describe this final epidemic, the controversy over compulsory vaccination, and ethical issues that remain relevant today.

Epidemiology and Protection through Vaccination

In May 1901, an outbreak of smallpox, initially unrecognized, was followed by a series of outbreaks in various neighborhoods of Boston.1 From 1901 to 1903, there were 1596 cases of smallpox (Figure 1), with 270 deaths,1,2,3 in a city with a population of approximately 560,900. The attack rate was 3 cases per 1000 persons, with a case fatality rate of 17 percent.


.../...


Opponents of Compulsory Vaccination

The Board of Health was concerned about criticism by the Anti–Compulsory Vaccination League and considered Boston "practically a hot-bed of the anti-vaccine heresy."21 Opponents of vaccination questioned its safety and efficacy. They believed that compulsory vaccination was a violation of civil liberties and that "from the standpoint of free citizenship no government should forcibly inflict on any individual enjoying all other rights of the nation, a disease [vaccine] loathsome in its origin, and not free from danger to life, and with, at all events, impairment of bodily health, at least of a temporary nature."22

In January 1902, legislation was proposed to repeal the state's compulsory-vaccination laws. The leading opponents of vaccination, including a number of physicians, testified in favor of the legislation.23 Arguing against the proposed repeal were prominent physicians, business leaders, and educators, including William Councilman, a pathologist at Harvard Medical School, and Frank Draper, the president of the Massachusetts Medical Society at the time. Those who supported vaccination prevailed, and in February, "all the antivaccination bills were reported adversely."24

This epidemic led to a landmark legal case on the constitutionality of compulsory vaccination.25,26 In Jacobson v. Massachusetts, a citizen challenged a Massachusetts law that allowed the Cambridge Board of Health to fine him for refusing revaccination. Jacobson argued that the law opposed "the inherent right of every freeman to care for his own body and health in such a way as to him seems best."25 In 1905, the U.S. Supreme Court voted seven to two in favor of the state, ruling that although the state could not pass laws requiring vaccination in order to protect an individual, it could do so to protect the public in the case of a dangerous communicable disease.

The Pfeiffer Affair

In November 1901, Durgin (the chairman of the Boston Board of Health) posed an extraordinary challenge: "If there are among the adult and leading members of the antivaccinationists any who would like an opportunity to show the people their sincerity in what they profess, I will make arrangements by which that belief may be tested and the effect of such exhibition of faith, by exposure to smallpox without vaccination, be made clear."27

In January 1902, Dr. Immanuel Pfeiffer, a Danish immigrant, requested that he be allowed to visit a smallpox hospital, ostensibly to study the disease, without undergoing vaccination. Pfeiffer, a physician who advocated fasting and hypnotism, was at one time president of the American Psychic Society.28 A vehement critic of the Board of Health, he apparently thought that people in good health were not at risk for contracting smallpox — a belief that was not representative of the views expressed by those who opposed vaccination. The Pfeiffer bill, which would have required "obtaining the consent to inject any poisonous substance into the body of any person,"29 was one of the antivaccination bills voted down in February 1902.

The 60-year-old Pfeiffer had not been vaccinated since infancy. In an unprecedented move, Durgin lifted the strict requirement of recent, successful vaccination for all health workers entering the Gallop's Island smallpox hospital. Pfeiffer visited the hospital on January 23, 1902, and was escorted among more than 100 patients with smallpox by the physician in charge, Dr. Paul Carson, who reportedly suggested that he smell the odor of a patient's breath.28 Health officers surreptitiously observed Pfeiffer after the visit, and on February 8, 1902, he was found to be critically ill in his home in Bedford. The following day, the headlines read, "Pfeiffer Has Smallpox. Anti-vaccinationist May Not Live."30 Physicians on the Board of Health initially predicted that Pfeiffer would die, but he survived. Durgin publicized the fact that no cases of smallpox had occurred among the recently vaccinated physicians who had visited the hospital. The press acknowledged his triumph: "Chairman Durgin comes up smiling."31 An editorial stated, "It is a salutary lesson to the anti-vaccinationists, and it is destined to live in the annals of preventive medicine."32

It is far from clear that the incident served as a "salutary lesson." Pfeiffer's theories on smallpox were his own, and opponents of compulsory vaccination were among those who condemned his "foolhardiness."33 One newspaper article questioned the ethics of Durgin's actions: "Was Dr. Durgin right in allowing Dr. Pfeiffer to visit the hospital without being vaccinated? . . . `It was the right thing to do, as it was good for the greatest number,' was the cool, analytical response of the chairman of the board of health."34 The Board of Health had not placed Pfeiffer under any restrictions after his exposure at Gallop's Island. The town of Bedford considered suing the city of Boston, charging that smallpox had been "imported because of the inexcusable negligence of the health authorities of Boston."35

Epilogue

After the epidemic ended, in March 1903, there were sporadic cases of smallpox in Boston. A total of 108 cases, 4 of which were fatal, were reported between October of that year and 1932, when the last case occurred.36 The controversy over vaccination persisted. After a failed attempt in 1926 to extend compulsory smallpox vaccination to children attending private schools, a Boston Health Department report complained bitterly about "active antivaccination propaganda."37 Smallpox made its final appearance in the United States in 1949, in Hidalgo County, Texas. In 1971, with no cases having been reported in the United States in the previous 22 years but with six to eight deaths per year due to complications of vaccination, the U.S. Public Health Service formally recommended the discontinuation of routine vaccination.38

This epidemic illustrates the importance of applying modern medical science (in this case, vaccination) to an acute public health problem, educating the medical community and the general public about the benefits of prevention, and having public debate on the pros and cons of public health policies aimed at prevention. Some aspects of the epidemic remain disturbing. The Board of Health's policy toward the homeless and the challenge to those who opposed vaccination to expose themselves to smallpox showed a disregard for civil liberties and for ethical concerns. Such abuses underscore the importance of an ethical framework for public health and medicine that includes the oath to "do no harm," respect for individual autonomy, and the requirement of informed consent.

With advances in the safety and efficacy of vaccines and a greater understanding of the immune system, public approval of vaccination increased in the 20th century. Ultimately, a concerted worldwide campaign based on immunization, surveillance, and containment of disease would achieve the goal of eradicating smallpox, which Edward Jenner had contemplated two centuries earlier.39,40



Michael R. Albert, M.D.
National Cancer Institute
Bethesda, MD 20892-1908

http://content.nejm.org/cgi/content/full/344/5/375
 
Thema: Impfen pro und Kontra: Neue Entwicklungen und Summary

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