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Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.

ABSTRACT: CD8(+) T cells that recognize virus-derived peptides presented on MHC class I are vital antiviral effectors. Such peptides presented by any given virus vary greatly in immunogenicity, allowing them to be ranked in an immunodominance hierarchy. However, the full range of parameters that determine immunodominance and the underlying mechanisms remain unknown. In this study, we show across a range of vaccinia virus strains, including the current clonal smallpox vaccine, that the ability of a strain to spread systemically correlated with reduced immunodominance. Reduction in immunodominance was observed both in the lymphoid system and at the primary site of infection. Mechanistically, reduced immunodominance was associated with more robust priming and especially priming in the spleen. Finally, we show this is not just a property of vaccine and laboratory strains of virus, because an association between virulence and immunodominance was also observed in isolates from an outbreak of zoonotic vaccinia virus that occurred in Brazil.

SUBMITTER: Flesch IE

PROVIDER: S-EPMC4546862 | biostudies-literature | 2015 Sep

REPOSITORIES: biostudies-literature

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Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.

Flesch Inge E A IE Hollett Natasha A NA Wong Yik Chun YC Quinan Bárbara Resende BR Howard Debbie D da Fonseca Flávio G FG Tscharke David C DC

Journal of immunology (Baltimore, Md. : 1950) 20150720 5

CD8(+) T cells that recognize virus-derived peptides presented on MHC class I are vital antiviral effectors. Such peptides presented by any given virus vary greatly in immunogenicity, allowing them to be ranked in an immunodominance hierarchy. However, the full range of parameters that determine immunodominance and the underlying mechanisms remain unknown. In this study, we show across a range of vaccinia virus strains, including the current clonal smallpox vaccine, that the ability of a strain ...[more]

PMID: 26195812

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Project description:BackgroundSmallpox was eradicated by 1980, but its possible use as a bioweapon has rekindled interest in the development of protective vaccines. Therefore, stockpiled calf lymph-derived vaccines and recently developed cell-cultured vaccines have been investigated to contribute information to smallpox emergency response plans, while newer (non-replication competent) vaccines are developed.ObjectivesTo assess the effects of smallpox vaccines in preventing the disease, in inducing immunity, and in regard to adverse events.Search strategyIn December 2006, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2006, Issue 4), MEDLINE, EMBASE, LILACS, and Current Controlled Trials, and handsearched Index Medicus. We also searched three databases of vaccine safety in December 2005.Selection criteriaRandomized controlled trials of smallpox vaccines versus placebo, other smallpox or non-smallpox vaccine, no intervention, or different dose of the same vaccine in people receiving smallpox vaccination irrespective of age.Data collection and analysisBoth authors independently assessed trial quality and extracted data. We combined dichotomous data using relative risk with a random-effects model.Main resultsTen trials involving 2412 participants were included. The vaccines investigated were calf-lymph derived first-generation vaccines (Dryvax, APVS, Lancy-vaxina, Lister), and cell-cultured second-generation vaccines (ACAM, CCSV). Vaccines were investigated in different dilutions. All undiluted vaccines induced a reaction in 95% of people vaccinated in terms of pustule and immunogenicity. Also 1:10 dilutions were fully efficient when the starting concentration was defined. Serious adverse events were reported in 1% to 2% of the volunteers. Fever was observed in 11% to 22% of participants, and headache in roughly half of the participants. Fever was less frequent when new vaccines were administered, but rates of headache were similar in new and old vaccines.Authors' conclusionsThe evidence shows that stockpiled vaccines have maintained their immunogenicity and new cell-cultured vaccines are similar to stockpiled vaccines in terms of vaccination success rate and immunogenicity. First- and second-generation vaccines diluted to at least 1:10 are as effective as undiluted vaccine in terms of clinical success rate and immunogenicity. Dilution did not reduce the frequency of adverse events. Success rate and immunogenicity were similar in naive and previously vaccinated persons, but there were fewer adverse events in previously vaccinated persons. The rate of adverse events found in this review reveals the need for further development and improvement of smallpox vaccines.

Dataset Information

Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.

Publications

Extent of Systemic Spread Determines CD8+ T Cell Immunodominance for Laboratory Strains, Smallpox Vaccines, and Zoonotic Isolates of Vaccinia Virus.

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