Vaccinia virus-specific CD8+ cytotoxic T lymphocytes in humans

Abstract

Stimulation of human vaccinia virus immune peripheral blood mononuclear cells in vitro from vaccinia virus-immune donors with live vaccinia virus-infected autologous cells generated vaccinia virus-specific cytotoxic T lymphocytes (CTL) capable of lysing vaccinia virus-infected cells. We generated vaccinia

LC16m8: An attenuated smallpox vaccine

“…The US FDA has published specific requirements for proof of efficacy in animal models that every new smallpox vaccine must meet (the so-called "animal rule") [68]. Given the multifactorial nature of the immune response to smallpox vaccines, various markers for both humoral and cellular immunity are being studied with the aim of identifying objective measurements of efficacy [41][42][43][92][93][94].…”

“…It is possible that the protection conferred by LC16m8 is B5R-independent and other EEV surface proteins may serve as epitopes for neutralizing antibodies [37,39,40]. There is also evidence that smallpox vaccines induce cell-mediated immunity (CMI) [41][42][43][44][45][46]. Hence it is possible that neutralizing epitopes on the truncated B5R protein might contribute to the overall protective immune response without being the primary mediator.…”

“…These included basic antibody and T-cell assays and monitoring of cutaneous responses to primary vaccination with LC16m8 [4]. However, current standards for determining vaccinia efficacy rely on more sophisticated measurements of humoral and CMI responses as well as lethal poxvirus challenges in vaccinated animal models [41,42,67,68]. One example of the latter is the lethal rabbitpox virus (RPXV) in rabbits, which mimics smallpox infection in humans [69] since it is rapidly and widely disseminated, is highly infectious, and produces high levels of EEV.…”

Flow Cytometry and T-Cell Response Monitoring after Smallpox Vaccination

“…Vigorous and long-lasting protective immune responses have been associated with smallpox vaccination, and specific immunity is believed to be maintained for decades (10,11). In long-term vaccinated persons, virus-specific CD4(+) and CD8(+) T-lymphocytes are detectable only after extensive in vitro culture and restimulation to generate antigen-specific lines or clones.…”

Establishment and Persistence of Virus‐Specific CD4+ and CD8+ T Cell Memory

“…Moreover, when considering memory, is it legitimate to assume that one mouse-year is indeed equivalent to 30 human years? Though there are indications that immune memory can persist for life in people exposed once to a viral pathogen, much of this is epidemiological (Matzinger 1994) in nature and (particularly for T cells) difficult (Demkowicz & Ennis 1993) to analyse with any degree of rigor. A measure of cross-protection against antigenically "shifted" influenza A viruses, which may be mediated by CDS* T cells specific for peptides derived from conserved internal proteins, is thought to be maintained for at least 3 years (McMichael 1994).…”