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PubMed1959

A study of the immunogenicity of smallpox vaccines.

The authors report on a series of tests to determine the immunogenic properties of smallpox vaccines of varying degrees of infectivity. Rabbits were immunized with serial dilutions of the vaccines and challenged twenty days later with intradermal neurovaccine or testicular vaccine, with injection of testicular vaccine into the testes, or with intracerebral neurovaccine. It was possible to demonstrate a correlation between the infectivity of the immunizing vaccine and the degree of immunity conferred, as shown by the serum antibody level and by the reaction to the challenge inoculation. It also appears that the immunogenicity of the vaccines is determined not only by the number of active virus particles they contain but also by their virulence, the more virulent giving greater immunity in smaller doses. Unduly virulent vaccines, however, may give rise in humans to severe and painful reactions.

Animals↗
PubMed1961

Observations on the classification and interpretation of reactions to smallpox vaccination.

Over the last ten years extensive trials have been carried out on various smallpox vaccines prepared by the Lister Institute of Preventive Medicine in England, and the opportunity has been taken to make careful records of the reactions encountered, to investigate the significance of the immediate reaction and to determine the relationship of techniques to vaccination failures.In this paper the various classifications of vaccination reactions are reviewed, and a modified system of classification is suggested, based on the experience of a large number of vaccinations performed with a uniform technique.The two main vaccination techniques (linear scratch and multiple pressure) are considered and evidence is adduced to suggest that the depth of insertion of the virus is the most important single factor contributing to successful vaccination. A standard scratch technique is recommended, which, by its speed and simplicity, is well suited to mass vaccination as well as to general use for individual patients.The problem of duration of immunity following successful vaccination is also discussed, experimental results suggesting that it is unusual to get a "revaccination vaccinia" reaction on revaccination within three years, providing the previous vaccination was successfully performed.

England↗
PubMed1962

Relationship between pock counts on chorio-allantoic membrane and percentages of "takes" in primary vaccination of human beings with two smallpox vaccines.

In view of doubts as to the potency level required to obtain nearly 100% successful vaccinations with the glycerolated smallpox vaccine prepared by the Netherlands National Institute of Public Health, its dose-effect relationship was compared with that of a glycerolated lymph from the Lister Institute of Preventive Medicine, England. The potency was estimated from pock counts on the chorio-allantoic membrane of chick embryos and the effect was judged from the "take" rate obtained in the primary vaccination of soldiers, the data being subjected to probit analysis.The relationship observed between the number of pock-forming units and the percentage of successful primary vaccinations was nearly identical with the two vaccines. The 50% effective doses were found to be 1.3-1.4 x 10(6) PFU/ml and the 99% doses to be 4.1-4.3 x 10(7) PFU/ml.

Allantois↗
PubMed1963

EVALUATION OF RESULTS OF THE TESTING OF SMALLPOX VACCINES. A REPORT ON STATISTICAL METHODS.

A report is given on the statistical methods used in the evaluation of results in the international assay of smallpox vaccines, and on special statistical problems connected with the counting of lesions (pocks and plaques).Variances due to different sources of error are estimated. These estimates are used to determine minimal testing programmes for detecting certain differences in relative vaccine potencies. Thus for comparison between three vaccines-each given in five dilutions-a minimum of two rabbits in the scarification test or 15 eggs in the pock counts (one egg per dilution) is required.To obtain the same variance in the scarification test as in the usual pock count programme (six eggs per dilution-i.e., 90 eggs for the three vaccines) 13 rabbits will be needed.

Animals↗
PubMed2004

A look behind the scenes: bioterrorism, smallpox, and public health policy.

The September 11, 2001 terrorist attacks on the World Trade Center and continued conflict in Middle Eastern countries has provoked a strong interest in issues of national security. On December 13, 2002 the Bush Administration announced its smallpox vaccination policy, the first nationwide "proactive" measure to address the threat of bioterrorism. The Program has received mixed reactions as a result of partisan issues, tensions in public health policy and federal and state jurisdiction, conflicting scientific views, and different risk assessments. The slow pace of the program, the difficulties surrounding its implementation, and the debates regarding its validity serves as a "case study" to demonstrate current short-comings in federal and state anti-terrorist and public health policies. The focus will be on the states' public health laws and emergency preparedness plans through an analysis of the proposed Model State Emergency Preparedness Act. Updating current public health laws combined with increased funding of scientific research and the foresight to act "proactively" will reach far beyond improving national security. These efforts serve the dual purpose of deterring future terrorist attacks while greatly improving responses to a number of other health emergencies and disasters.

Biological Warfare↗
PubMed2004

[Should the human smallpox virus (variola) be destroyed?].

Smallpox, caused by variola virus, was a terror for civilizations around the world for more than 3000 years. Although the disease is eradicated, hundreds of variola virus isolates are kept in two WHO-collaborating facilities, one in USA and one in Russia. In spite of several agreements on destruction, it is now doubtful that these virus isolates will be destroyed. Variola virus may exist in other places and may be used as a biological weapon in war or for terror. Further research on variola virus is thus essential in order to achieve a better understanding of the pathogenicity of the virus and to develop new anti-variola virus vaccines and antiviral drugs.

Biomedical Research↗
PubMed1977

[Immunological characteristics of the 2-stage method of smallpox vaccination].

As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained.

Antibodies, Viral↗
PubMed1990

[Various memorable dates from the history of smallpox vaccination].

Several dates of memory from the history of the vaccination against smallpox are to be registered for the year 1990. The birthday of the vaccination propagandist Johann Adam Reimann comes round the 300th time, the initial date of relevant university instructions comes round the 200th time. Issuing from this the history of vaccination against small pox is touched on at the instance of several marking points.

Europe↗
PubMed1979

[Patterns of the cytogenetic changes in the peripheral blood lymphocytes of children immunized against smallpox and parotitis].

A positive correlation between the frequency of acrocentric chromosome associations (AChA) and the accumulation of antibody titers in children immunized against smallpox and parotiditis has been discovered. The decrease of AChA in proliferating lymphocytes is accompanied with the lowering of D/G ratio due to group G predomination in AChA. The aberration frequency was kept unchanged throughout the whole observation of children immunized against parotiditis. A lower degree of cytogenic alterations in lymphocytes and accumulation of titers of antibodies in children immunized against paratiditis, as compared with those in the other group, may suggest a weak immunological effect of the given inoculative preparation.

Child↗
PubMed1972

Assay of neutralizing antibody against variola virus by the degree of focus reduction on HeLa cell cultures and its application to revaccination with smallpox vaccines of various potencies.

A method for assaying neutralizing antibody against variola virus was established by focus counting on HeLa cell cultures. The ND(50) titre, i.e., the serum dilution endpoint to give a 50% reduction in the number of foci, was determined with excellent reproducibility.Groups of students 19-20 years of age were revaccinated by the multiple pressure method with serial 10-fold dilutions of a smallpox vaccine and their neutralizing antibody response was assayed by the focus counting assay system and was related to the local skin reactions on the seventh day after inoculation and to the potency of the vaccine administered. There was a significant rise in the antibody level even after inoculation with a vaccine whose potency was as low as 1.3 x 10(5) pock-forming units/ml. In general, the rise in the log antibody level was proportional to the diameter of the reddening, but a significant rise was found among individuals who had no detectable skin reaction. The skin reaction was greater among individuals with a lower initial antibody level when the vaccine administered had a potency lower than 1.3 x 10(6) pock-forming units/ml.

Adult↗
PubMed1974

Pattern of intrafamilial transmission of smallpox in Calcutta, India.

The pattern of intrafamilial transmission of smallpox in Calcutta was studied in 43 index cases, 3 of which were haemorrhagic, 14 confluent, and 26 discrete. They had 741 contacts. The attack rate in vaccinated contacts was significantly less than in unvaccinated contacts, but there was no such difference in the case rates caused by severe and mild index cases. Females had higher attack rates than males, the difference being more marked among the vaccinated. The vaccination status of the index cases seemed to affect their secondary case rates. The incidence of secondary cases among contacts living in the same room as a patient and in other rooms in the same compound was practically equal.

Adolescent↗
PubMed1972

Cutaneous responses to smallpox revaccination with calf lymph and the effect of fluorocarbon purification of the vaccine.

For several years the routine smallpox revaccination procedures at a central inoculation unit were arranged to assess the relation between vaccine titre (pock count) and success. Calf lymph batches were applied, diluted and undiluted, over a log titre range of 7.0-9.8. The dose-effect relationship did not appear to fit a linear equation on a log-probit scale, except in the lower part of the titre range. Plotted on this scale, the take rates of nearly all vaccine specimens of the required strength (> 10(8) PFU/ml) were lower than anticipated by linear extrapolation from low titres. Differences between batches were noted. These findings relate to pulp processing without purification. Fluorocarbon extraction of the calf skin harvest resulted in a 4-fold increase of vaccine volume with commensurate virus dilution; it also gave clearly higher take rates than parallel nonpurified vaccine specimens, whether at original strength or at 4-fold dilution.

Animals↗
PubMed1973

Simultaneous administration of smallpox, measles, yellow fever, and diphtheria-pertussis-tetanus antigens to Nigerian children.

Children receiving smallpox, measles, and yellow fever vaccines simultaneously at separate sites responded adequately to all three vaccines. In those children, 9 months of age and older, who received these three vaccines in addition to diphtheria-pertussis-tetanus vaccine, there was a decrease in measles seroconversion rates from 89% to 70%. Possible interactions between live and killed vaccines should be considered when the administration of multiple antigens is planned.

Antibodies, Bacterial↗
PubMed1971

Complications of smallpox vaccination, 1968. Results of a statewide survey in Alaska.

A survey was made to determine the incidence in Alaska of complications of smallpox vaccination during 1968. Of the 206 medical personnel responding to the questionnaire, 20 (or 9.7 percent) observed a complication. Twenty-six complications were reported, 20 of which occurred in primary vaccinees. Accidental implantation was the most common complication, but two cases of eczema vaccinatum and two of generalized vaccinia were observed. There were no deaths or cases of postvaccinial encephalitis or vaccinia necrosum. Of the 26 complications, 19 were theoretically preventable.

Adolescent↗
PubMed1970

Comparative studies of smallpox vaccination by the bifurcated needle and rotary lancet techniques.

Comparisons were made in groups of schoolchildren in New Delhi of the rotary lancet and bifurcated needle techniques for primary vaccination and revaccination against smallpox. Vaccines of 3 different titres were employed in the tests. The results indicate that the bifurcated needle technique is superior to the rotary lancet technique for both primary vaccination and revaccination, the percentage of major reactions in revaccinations in which the bifurcated needle technique was used being significantly higher, irrespective of the vaccine dilution. However, the proportion of major reactions decreased gradually in both techniques with the greater dilution of the vaccine.It was shown that when a fully potent vaccine is used there is no advantage in making 2 insertions by the bifurcated needle technique but that when the rotary lancet technique is employed and when the vaccine is not fully potent there is a significant improvement in the successful take rate when 2 insertions are given. In areas where storage facilities for vaccines in the field are not ideal and the full potency of vaccines is doubtful, the use of the bifurcated needle technique with 2 insertions seems to be the method of choice.

Child↗
PubMedDate not supplied

[Smallpox vaccination with protection by interferon and an interferon inducer].

The vaccinal process was studied in monkeys vaccinated with smallpox vaccine under the protection of fibroblastic or leukocytic interferons and modified poly(I) . poly(C). Simultaneous vaccination and administration of one of the studied preparations induced intense immunity and at the same time prevented viremia and alleviated local inflammatory reactions caused by the vaccination. The protective effect of the fibroblastic interferon was more marked than that of the leukocytic one in the vaccinal process. When the monkeys received the preparations intramuscularly the leukocytic but not the fibroblastic interferon was detected in the blood.

Animals↗
PubMedDate not supplied

[Determination of the take efficiency of lyophilized smallpox vaccine as a function of the vaccination technic (double scarification, multi-puncture and jet injection)].

Revaccination against smallpox was performed by three techniques: double scarification, multiple puncture and jet injection in 352 youths aged 16 and 17 years. The results were assessed by the number of takes, the quality of the cutaneous and humoral response. The highest proportion of major skin reactions was obtained by multiple puncture vaccination (62.4%) and the best humoral response, tested by passive haemagglutination, by jet revaccination. Multiple puncture is recommended as a method of election both in restricted and mass vaccination in view of the high proportion of major skin rections accompanied by a corresponding humoral response, the rapid and readily performed technique and small amount of vaccine needed.

Adolescent↗
PubMedDate not supplied

[Immunopathological circumstances in the structure of complications appearing after smallpox vaccination].

Investigations were carried out concerning the dynamics of antivaccinal antibodies and the structure of serum proteins in relation to the clinical manifestations following upon smallpox vaccination. In general, immunity is not apparently influenced by postvaccinal complications may be associated with immunoprotein perturbations, manifested by an increase in the alpha2-globulin fraction and, inconstantly, in the gamma-globulin fraction. Immunoelectrophoretic determinations revealed a relatively constant IgM and IgG deficiency. Postvaccinal dysglobulinemia may accompany various clinical forms, suggesting a temporary deficient immunological response. In one case of agammaglobulinemia, revaccination produced a deep vaccinal ulcer, with extensive necrosis (giant necrotic vaccinia). In order to decipher the substrate of the reaction in the clinical forms with distal manifestations or generalized vaccinia, skin biopsies were performed. The lesional vasculoallergic substrate of the skin lesions does not exclude the local aggression of the vaccinal virus, which was isolated by viral determinations.

Adolescent↗