State of Alaska Epidemiology Bulletin: Smallpox vaccination: Normal and adverse reactions to vaccinia virus

2003 ◽  
Keyword(s):  
Vaccinia Virus ◽  
Adverse Reactions ◽  
Smallpox Vaccination

scholarly journals Persisting Humoral Antiviral Immunity within the Japanese Population after the Discontinuation in 1976 of Routine Smallpox Vaccinations

2005 ◽  
Vol 12 (4) ◽  
pp. 520-524 ◽  
Author(s):  
Shuji Hatakeyama ◽  
Kyoji Moriya ◽  
Masayuki Saijo ◽  
Yuji Morisawa ◽  
Ichiro Kurane ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Japanese Population ◽  
Neutralizing Antibodies ◽  
Antiviral Immunity ◽  
Smallpox Vaccination ◽  
Considerable Proportion ◽  
Enzyme Linked Immunosorbent Assay ◽  
Specific Immunoglobulin ◽  
Specific Igg ◽  
Induced Immunity

ABSTRACT Concerns have arisen recently about the possible use of smallpox for a bioterrorism attack. Routine smallpox vaccination was discontinued in Japan in 1976; however, it is uncertain exactly how long vaccination-induced immunity lasts. We sought to evaluate the seroprevalence and intensity of anti-smallpox immunity among representatives of the present Japanese population. The subjects included 876 individuals who were born between 1937 and 1982. Vaccinia virus-specific immunoglobulin G (IgG) levels were measured by enzyme-linked immunosorbent assay (ELISA), and 152 of 876 samples were also tested for the presence of neutralizing antibodies. Of the subjects who were born before 1962, between 1962 and 1968, and between 1969 and 1975, 98.6, 98.6, and 66.0%, respectively, still retained the vaccinia virus-specific IgG with ELISA values for optical density at 405 nm (OD405) of ≥0.10. The corresponding figures for retained IgGs with OD405 values of ≥0.30 were 91.0, 90.3, and 58.2%, respectively. Neutralizing antibodies were also maintained. The sera with OD405 values of ≥0.30 showed 89% sensitivity and a 93% positive predictive value for detection of neutralizing antibodies (≥4). Thus, approximately 80% of persons born before 1969 and 50% of those born between 1969 and 1975 were also found to have maintained neutralizing antibodies against smallpox. A considerable proportion of the previous vaccinated individuals still retain significant levels of antiviral immunity. This long-lasting immunity may provide some protective benefits in the case of reemergence of smallpox, and the disease may not spread as widely and fatally as generally expected.

scholarly journals Effect of the Route of Administration of the Vaccinia Virus Strain LIVP to Mice on Its Virulence and Immunogenicity

Viruses ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 795
Author(s):  
Sergei N. Shchelkunov ◽  
Stanislav N. Yakubitskiy ◽  
Alexander A. Sergeev ◽  
Alexei S. Kabanov ◽  
Tatiana V. Bauer ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Vaccinia Virus ◽  
Vaccination Campaign ◽  
Lethal Dose ◽  
Clinical Manifestations ◽  
Immune Defense ◽  
Smallpox Vaccination ◽  
Laboratory Animals ◽  
Optimal Method ◽  
Clonal Variant

The mass smallpox vaccination campaign has played a crucial role in smallpox eradication. Various strains of the vaccinia virus (VACV) were used as a live smallpox vaccine in different countries, their origin being unknown in most cases. The VACV strains differ in terms of pathogenicity exhibited upon inoculation of laboratory animals and reactogenicity exhibited upon vaccination of humans. Therefore, each generated strain or clonal variant of VACV needs to be thoroughly studied in in vivo systems. The clonal variant 14 of LIVP strain (LIVP-14) was the study object in this work. A comparative analysis of the virulence and immunogenicity of LIVP-14 inoculated intranasally (i.n.), intradermally (i.d.), or subcutaneously (s.c.) to BALB/c mice at doses of 108, 107, and 106 pfu was carried out. Adult mice exhibited the highest sensitivity to the i.n. administered LIVP-14 strain, although the infection was not lethal. The i.n. inoculated LIVP-14 replicated efficiently in the lungs. Furthermore, this virus was accumulated in the brain at relatively high concentrations. Significantly lower levels of LIVP-14 were detected in the liver, kidneys, and spleen of experimental animals. No clinical manifestations of the disease were observed after i.d. or s.c. injection of LIVP-14 to mice. After s.c. inoculation, the virus was detected only at the injection site, while it could disseminate to the liver and lungs when delivered via i.d. administration. A comparative analysis of the production of virus-specific antibodies by ELISA and PRNT revealed that the highest level of antibodies was induced in i.n. inoculated mice; a lower level of antibodies was observed after i.d. administration of the virus and the lowest level after s.c. injection. Even at the lowest studied dose (106 pfu), i.n. or i.d. administered LIVP-14 completely protected mice against infection with the cowpox virus at the lethal dose. Our findings imply that, according to the ratio between such characteristics as pathogenicity/immunogenicity/protectivity, i.d. injection is the optimal method of inoculation with the VACV LIVP-14 strain to ensure the safe formation of immune defense after vaccination against orthopoxviral infections.

Preemptive Tecovirimat Use in an Active Duty Service Member Who Presented With Acute Myeloid Leukemia After Smallpox Vaccination

2019 ◽  
Vol 69 (12) ◽  
pp. 2205-2207 ◽  
Author(s):  
David A Lindholm ◽  
Raymond D Fisher ◽  
Jay R Montgomery ◽  
Whitni Davidson ◽  
Patricia A Yu ◽  
...  
Keyword(s):  
Acute Myeloid Leukemia ◽  
Acute Leukemia ◽  
Treatment Strategy ◽  
Myeloid Leukemia ◽  
Adverse Reactions ◽  
Active Duty ◽  
Service Member ◽  
Smallpox Vaccination ◽  
Increased Risk ◽  
Acute Myeloid

Abstract Smallpox vaccine is contraindicated in immunosuppression due to increased risk for adverse reactions (eg, progressive vaccinia). We describe the first-ever use of tecovirimat as a preemptive vaccinia virus treatment strategy during induction chemotherapy in an active duty service member who presented with acute leukemia and inadvertent autoinoculation after smallpox vaccination.

Absence of oropharyngeal vaccinia virus after vaccinia (smallpox) vaccination

2005 ◽  
Vol 94 (6) ◽  
pp. 682-685 ◽  
Author(s):  
Mary M. Klote ◽  
George V. Ludwig ◽  
Melanie P. Ulrich ◽  
Lisa A. Black ◽  
Dallas C. Hack ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Smallpox Vaccination

scholarly journals Failure of the Smallpox Vaccine To Develop a Skin Lesion in Vaccinia Virus-Naïve Individuals Is Related to Differences in Antibody Profiles before Vaccination, Not After

2012 ◽  
Vol 19 (3) ◽  
pp. 418-428 ◽  
Author(s):  
Xiaolin Tan ◽  
Sookhee Chun ◽  
Jozelyn Pablo ◽  
Philip Felgner ◽  
Xiaowu Liang ◽  
...  
Keyword(s):  
Skin Lesion ◽  
Antibody Response ◽  
Vaccinia Virus ◽  
Smallpox Vaccination ◽  
Unknown Etiology ◽  
Before And After ◽  
Antibody Titers ◽  
Antibody Profiling ◽  
Different Doses ◽  
Protein Enzyme

ABSTRACTSuccessful vaccination against smallpox with conventional vaccinia virus is usually determined by the development of a vesicular skin lesion at the site of vaccinia inoculation, called a “take.” Although previous vaccination is known to be associated with attenuation of the take, the immunology that underlies a no-take in vaccinia-naïve individuals is not well understood. We hypothesized that antibody profiling of individuals before and after receiving vaccinia virus would reveal differences between takes and no-takes that may help better explain the phenomenon. Using vaccinia virus proteome microarrays and recombinant protein enzyme-linked immunosorbent assays (ELISAs), we first examined the antibody response in vaccinia-naïve individuals that failed to take after receiving different doses of the replication-competent DryVax and Aventis Pasteur (APSV) smallpox vaccines. Most that received diluted vaccine failed to respond, although four no-takes receiving diluted vaccine and four receiving undiluted vaccine mounted an antibody response. Interestingly, their antibody profiles were not significantly different from those of controls that did show a take. However, we did find elevated antibody titers in no-takes prior to receiving DryVax that were significantly different from those of takes. Although the sample size studied was small, we conclude the failure to take in responders correlates with preexisting immunity of unknown etiology that may attenuate the skin reaction in a way similar to previous smallpox vaccination.

scholarly journals ROUTE-COUPLED PATHOGENICITY AND IMMUNOGENICITY OF VACCINIA VIRUS VARIANT INOCULATED MICE

2019 ◽  
Author(s):  
S. Shchelkunov ◽  
A. Sergeev ◽  
A. Kabanov ◽  
S. Yakubitskyi ◽  
T. Bauer ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Virus Strain ◽  
Dna Sequences ◽  
Virulence Genes ◽  
Clinical Manifestations ◽  
World Health ◽  
Smallpox Vaccination ◽  
Natural Evolution ◽  
Vaccinia Virus Strain ◽  
Virus Strains

Vaccinia virus had played a key role in the global smallpox eradication. However, in case of mass vaccination with various vaccinia virus strains severe side effects were revealed sometimes ending up with lethal outcomes, especially in immunocompromised humans. Hence, the World Health Organization recommended to cancel smallpox vaccination after declaring in 1980 about smallpox eradication. Over last 40 years, human population virtually lost immunity not only against smallpox, but also against other zoonotic orthopoxvirus infections, such as monkeypox, cowpox, buffalopox, and camel pox. All of them pose an represent increasing threat to human health and heighten a risk of emerging highly contagious viruses due to natural evolution of previous zoonotic orthopoxviruses. In order to prevent development of small outbreaks into spreading epidemics and, thus, to decrease a risk of emergence due to natural evolution of highly pathogenic for humans orthopoxviruses, efforts should be applied to develop safe new generation live vaccines based on vaccinia virus with target virulence genes inactivation. These strains should be examined in laboratory animal models inoculated via different routes. Currently, vaccinia virus often becomes attenuated to create live recombinant vaccines due to inserting target DNA sequences into the virus virulence genes resulting in their inactivation. Vaccinia virus strain LIVP used in the Russian Federation as smallpox vaccine as well as derivative attenuated variant LIVP-GFP created by using genetic engineering methods with inactivating its thymidine kinase gene were examined.Such viruses were intracerebrally inoculated into suckling mice at doses of 101 or 102 PFU/animal for neurovirulence assessment. Adult mice were infected intranasally, subcutaneously or intradermally at doses of 107 or 108 PFU/animal and clinical manifestations were analyzed for 14 days. On 28 day after the onset, blood serum samples were collected from individual mice to measure virus specific antibody level by using ELISA. It was shown that recombinant vaccinia virus strain LIVP-GFP displayed markedly lowered neurovirulence and pathogenicity for mice as compared to parental LIVP. Finally, intradermal route turned out to demonstrate the most safe and effective profile for immunization with both examined vaccinia virus strains.

scholarly journals Differential Response Following Infection of Mouse CNS with Virulent and Attenuated Vaccinia Virus Strains

Vaccines ◽  
2019 ◽  
Vol 7 (1) ◽  
pp. 19
Author(s):  
Tomer Israely ◽  
Nir Paran ◽  
Noam Erez ◽  
Lilach Cherry ◽  
Hadas Tamir ◽  
...  
Keyword(s):  
Vaccinia Virus ◽  
Viral Infections ◽  
Adaptive Immune Response ◽  
Viral Clearance ◽  
Smallpox Vaccination ◽  
Cns Infection ◽  
Rna Seq ◽  
Tissue Integrity ◽  
Brain Infection ◽  
The Central Nervous System

Viral infections of the central nervous system (CNS) lead to a broad range of pathologies. CNS infections with Orthopox viruses have been mainly documented as an adverse reaction to smallpox vaccination with vaccinia virus. To date, there is insufficient data regarding the mechanisms underlying pathological viral replication or viral clearance. Therefore, informed risk assessment of vaccine adverse reactions or outcome prediction is limited. This work applied a model of viral infection of the CNS, comparing neurovirulent with attenuated strains. We followed various parameters along the disease and correlated viral load, morbidity, and mortality with tissue integrity, innate and adaptive immune response and functionality of the blood–brain barrier. Combining these data with whole brain RNA-seq analysis performed at different time points indicated that neurovirulence is associated with host immune silencing followed by induction of tissue damage-specific pathways. In contrast, brain infection with attenuated strains resulted in rapid and robust induction of innate and adaptive protective immunity, followed by viral clearance and recovery. This study significantly improves our understanding of the mechanisms and processes determining the consequence of viral CNS infection and highlights potential biomarkers associated with such outcomes.

SMALLPOX VACCINATION WITH PROLONGED VACCINIA

PEDIATRICS ◽  
1951 ◽  
Vol 7 (1) ◽  
pp. 24-33
Author(s):  
JOHN A. BIGLER ◽  
EUGENE L. SLOTKOWSKI
Keyword(s):  
Epithelial Cells ◽  
Vaccinia Virus ◽  
Direct Action ◽  
Smallpox Vaccination ◽  
Specific Antibodies ◽  
Probable Reason ◽  
The Third ◽  
Full Development ◽  
Humoral Antibodies

Definite clinical, histologic and immunologic changes take place following smallpox vaccination. After its full development on the ninth or tenth day, the vaccinial lesion is followed by drying, crusting and scarring. Histologically, there are degenerative and irritative changes in the epidermis believed to be due to the direct action of the virus on the epithelial cells. Immunologically, humoral antibodies to vaccinia begin to appear at the end of the first week following cutaneous vaccination, increase in amount during the second and third weeks and reach a maximum at the end of the third week. The probable reason for the involution of the vaccinial lesion after the pustular stage is the appearance of specific antibodies in the blood which apparently neutralize the vaccinia virus. The presence of histologically active vaccinial lesions approximately four months after implantation of the vaccinia virus could only be explained on the inability of the child to develop immunity to the vaccinia virus. Because of this lack of immunity, degenerative action of the vaccinia virus continued unopposed.

STUDIES ON SMALLPOX AND COMPLICATIONS OF SMALLPOX VACCINATION

PEDIATRICS ◽  
1960 ◽  
Vol 26 (2) ◽  
pp. 176-189
Author(s):  
C. Henry Kempe
Keyword(s):  
Vaccinia Virus ◽  
Clinical Observation ◽  
Gamma Globulin ◽  
Smallpox Vaccination ◽  
Passive Immunity ◽  
Early Assessment ◽  
Therapeutic Experience ◽  
The Past ◽  
Principal Subject ◽  
Fruitful Field

Introductory remarks the presentation of the E. Mead Johnson Award affords the recipient the honor of publicly acknowledging his debts to his teachers. I pay such grateful tribute to Dr. Grover Powers and Dr. Edward B. Shaw, my preceptors in academic pediatrics and to Dr. Joseph Smadel who introduced me to the pox viruses and urged me to take another look at the well-trodden field of smallpox. Helpful in his own way was the senior virologist who urged me instead to get involved in another, more fruitful field because "smallpox leaves no room for further work, having been well studied in the 1920's" and who, thereby, strengthened my resolve to re-examine current concepts in the field of smallpox and smallpox vaccination, a subject which has occupied us for the past 14 years. I also acknowledge my lasting debt to my associate, Dr. Henry Silver, who has been a critical colleague, supporter and friend over many years. The WELL KNOWN clinical observation that it is sometimes difficult to vaccinate the very young chi'd against smallpox led to our early assessment of passive immunity as a modifying factor1 and this, in turn, resulted in the development of hyper-immune vaccinal gamma-globulin and its use in the prevention of smallpox after known exposure.2 The principal subject of this report will be our therapeutic experience with hyperimmune vaccinal gamma-globulin in over 300 patients suffering from serious complications of smallpox vaccination. Finally, we hope to show how basic immunologic studies can be of great value in the management of some of the unfortunate patients whose experience with the vaccinia virus has been a tragic one.

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