Smallpox Vaccination: A Review, Part II. Adverse Events

Fulginiti, Vincent A.; Papier, Arthur; Lane, John; Neff, John M.; Henderson, Donald A.

doi:10.1086/375825

Cited by 199 publications

(145 citation statements)

References 45 publications

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“…Concerns that variola virus might be used as a biological weapon, however, have reawakened interest in protective vaccines and therapeutics (1). The licensed smallpox vaccines, consisting of live vaccinia virus, confer longlasting immunity against closely related orthopoxviruses, including variola virus, but routinely produce pustular skin lesions and infrequent but severe side reactions (2,3). Consequently, the vaccine is contraindicated for many millions of people and their close contacts with histories of eczema, atopic dermatitis, immunodeficiency, or heart disease.…”

mentioning

confidence: 99%

Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge

Wyatt

Earl

Eller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

226

231

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Modified vaccinia virus Ankara (MVA), developed >30 years ago as a highly attenuated candidate smallpox vaccine, was recloned from a 1974 passage and evaluated for safety and immunogenicity. Replication of MVA is impaired in most mammalian cells, and we found that mice with severe combined immunodeficiency disease remained healthy when inoculated with MVA at 1,000 times the lethal dose of vaccinia virus derived from the licensed Dryvax vaccine seed. In BALB͞c mice inoculated intramuscularly with MVA, virus-specific CD8 ؉ T cells and antibodies to purified virions and membrane protein components of the intracellular and extracellular infectious forms of vaccinia virus were induced in a dosedependent manner. After one or two inoculations of MVA, the T cell numbers and antibody titers equaled or exceeded those induced by percutaneous injection of Dryvax. Antibodies induced by MVA and Dryvax were neutralizing and inhibited virus spread in cultured cells. Furthermore, vaccinated mice were protected against lethal intranasal challenge with a pathogenic vaccinia virus. B cell-deficient mice unable to generate antibodies and ␤2-microglobulin-deficient mice unable to express MHC class I molecules for a CD8 ؉ T cell response were also protectively vaccinated by MVA. In contrast, mice with decreased CD4 or MHC class II expression and double-knockout mice deficient in MHC class Iand II-restricted activities were poorly protected or unprotected. This study confirmed the safety of MVA and demonstrated that the overlapping immune responses protected normal and partially immune-deficient animals, an encouraging result for this candidate attenuated smallpox vaccine.

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mentioning

confidence: 99%

Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge

Wyatt

Earl

Eller

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

226

231

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“…sponse to achieve viral clearance, vaccinees with T cell defects failed to control the infection after immunization (2,3).…”

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confidence: 99%

Long-Term Immunity against Actual Poxviral HLA Ligands as Identified by Differential Stable Isotope Labeling

Meyer

Kastenmüller

Gasteiger

et al. 2008

The Journal of Immunology

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Viral peptides are presented by HLA class I on infected cells to activate CD8+ T cells. Several immunogenic peptides have been identified indirectly by epitope prediction and screening of T cell responses to poxviral vectors, including modified vaccinia virus Ankara (MVA) currently being tested as recombinant or smallpox vaccines. However, for the development of optimal vaccination and immunomonitoring strategies, it is essential to characterize the actual viral HLA ligand repertoire of infected cells. We used an innovative approach to identify naturally processed MVA HLA ligands by differential HPLC-coupled mass spectrometry. We describe 12 viral peptides presented by HLA-A*0201 and 3 by HLA-B*0702. All HLA-A*0201 ligands participated in the memory response of MVA-immune donors, and several were immunogenic in Dryvax vaccinees. Eight epitopes were novel. Viral HLA ligand presentation and viral protein abundance did not correlate. All ligands were expressed early during the viral life cycle, and a pool of three of these mediated stronger protection against a lethal challenge in mice as compared with late epitopes. This highlights the reliability of the comparative mass spectrometry-based technique to identify relevant viral CD8+ T cell epitopes for optimizing the monitoring of protective immune responses and the development of effective peptide-based vaccines.

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“…Although vaccination is generally safe and effective for prevention of smallpox, it is well documented that various adverse reactions in individuals have been caused by vaccination with existing licensed vaccines (2). Vaccinia immune globulin (VIG) prepared from vaccinated humans has historically been used to treat adverse reactions arising from VACV immunization (3)(4)(5)(6), and, to date, VIG is still the only recommended treatment (5,6).…”

mentioning

confidence: 99%

Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus

Chen

Earl²,

Americo³

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

120

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Smallpox Vaccination: A Review, Part II. Adverse Events

Cited by 199 publications

References 45 publications

Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge

Highly attenuated smallpox vaccine protects mice with and without immune deficiencies against pathogenic vaccinia virus challenge

Long-Term Immunity against Actual Poxviral HLA Ligands as Identified by Differential Stable Isotope Labeling

Chimpanzee/human mAbs to vaccinia virus B5 protein neutralize vaccinia and smallpox viruses and protect mice against vaccinia virus

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