Samuel Stanley

Washington University in St. Louis, San Luis, Missouri, United States

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Publications (4)48.91 Total impact

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    ABSTRACT: Background: Orthopoxviruses produce inhibitors of complement enzymes that are structurally and functionally homologous to human regulators of complement activation. Vaccinia virus complement control protein (VCP) is one such protein that inhibits complement-mediated vaccinia virus neutralization. It is not known if humans vaccinated with smallpox vaccines elicit anti-VCP antibodies, which may have implications for orthopoxvirus immunity. Methods: Sera drawn at days 0, 30 and 360 post-vaccination from 40 randomly selected vaccinia-naïve subjects in a Phase I trial of the vaccinia virus smallpox vaccine LC16m8 were analyzed for IgG by ELISA. Thirty-two subjects received LC16m8, and eight received the comparator vaccine, Dryvax. Categorical variables were compared by chi-square or Fisher’s exact test. End point titers were aggregated as geometric mean titers (GMT) and compared between groups by independent samples t-tests of log-transformed data. Results: Low-level anti-VCP antibodies were detected in one (3%) subject at baseline. Anti-VCP antibodies were detectable 30 days post-vaccination in 35 (88%) subjects, with no difference between the two vaccine groups (28 [88%] LC16m8 recipients, 7 [88%] Dryvax recipients). Day 30 anti-VCP antibody titers were similar in the two groups (GMT 651 for LC16m8 vs. 765 for Dryvax, p=0.77). Anti-VCP antibodies remained detectable 360 days after vaccination in both vaccine groups (19 [59%] LC16m8 recipients, 6 [75%] Dryvax recipients, p=0.41), however there was a trend toward higher titers in the Dryvax arm (GMT 116 for LC16m8 vs. 237 for Dryvax, p=0.08). Conclusion: Vaccination with the smallpox vaccines LC16m8 and Dryvax elicit similarly robust anti-VCP antibody responses in vaccinia-naïve subjects. Further studies are in progress to assess the ability of these antibodies to block the function of VCP.
    Infectious Diseases Society of America 2007 Annual Meeting; 10/2007
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    ABSTRACT: For a brief period, modern medical science was considered to have relegated infectious disease to that of a minor clinical challenge. However, several infectious diseases have emerged or re-emerged in recent years, raising epidemiological concerns, as well as issues over the availability of effective measures of control and treatment. Invariably, these infectious agents have been studied carefully in relation to the safety of blood products, often resulting in concern and action. Emerging diseases arise from many sources. Some are the result of viruses crossing the species barrier from animals to humans. In addition, combinations of these newly identified viruses may make each more difficult to treat, as in the case of human immunodeficiency virus and hepatitis C virus coinfection. Still others can arise from completely new biological mechanisms, such as the prion disease variant Creutzfeldt-Jacob disease, which has spread from infected cattle to humans, particularly in the United Kingdom. The emergence of new viruses and new disease sources has had a significant impact on coagulation factor therapies and blood donation policies. We must deal with these multiple threats and their potential to compromise the safety of our blood supply.
    Seminars in Thrombosis and Hemostasis 07/2006; 32 Suppl 2:3-9. DOI:10.1055/s-2006-946908 · 3.69 Impact Factor
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    ABSTRACT: As a result of immunological and nucleic-acid screening of plasma donations for transfusion-transmissible viruses, and the incorporation of viral reduction processes during plasma fractionation, coagulation-factor concentrates (CFC) are now judged safe in terms of many known infectious agents, including hepatitis B and C viruses, HIV, and human T-cell lymphotropic virus. However, emerging pathogens could pose future threats, particularly those with blood-borne stages that are resistant to viral-inactivation steps in the manufacturing process, such as non-lipid-coated viruses. As outlined in this Review, better understanding of infectious diseases allows challenges from newly described agents of potential concern in the future to be anticipated, but the processes of zoonotic transmission and genetic selection or modification ensure that plasma-derived products will continue to be subject to infectious concerns. Manufacturers of plasma-derived CFC have addressed the issue of emerging infectious agents by developing recombinant products that limit the need for human plasma during production. Such recombinant products have extended the safety profile of their predecessors by ensuring that all reagents used for cell culture, purification steps, and stabilisation and storage buffers are completely independent of human plasma.
    The Lancet 02/2006; 367(9506):252-61. DOI:10.1016/S0140-6736(06)68036-7 · 45.22 Impact Factor
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    ABSTRACT: Background: Vaccinia virus membrane proteins B5R, A33R and A27L are candidates for inclusion in smallpox subunit vaccines. The kinetics of antibody (Ab) responses to these proteins after standard smallpox vaccination may help guide vaccine development. Methods: IgG enzyme-linked immunosorbent assays were used to measure anti-B5R, -A33R, and -A27L Abs in sera from previous vaccinia [Dryvax] clinical trials. Time points studied were baseline, and 2 weeks (W2), 1 month (M1), and 1, 2, & 3 years (Y1-Y3) post-vaccination in 20 vaccinia-naïve (never vaccinated) and 18 non-naïve (previously vaccinated) healthy adults. Results: 1) Naïve vaccinees. All Abs peaked at M1. A27L and A33R displayed high peak titers (geometric mean titers [GMT] 956 and 917) that declined 5-fold to stable levels by Y1 (GMT-204 and 193). B5R Abs peaked lower (GMT-260), but persisted with little decay through Y3 (GMT-186). 2) Non-naïve vaccinees. Abs were detected at baseline in 33% of A27L (GMT-88), 67% of A33R (GMT-147), and 72% of B5R (GMT-222). All Abs peaked at W2. B5R Abs were vigorously boosted with peak titers 7.5-fold higher than peaks for naïve vaccinees (GMT-1954), and remained at twice baseline through Y2. A27L and A33R peak titers (GMT A27L-521, A33R-445) were only half those of first time vaccinees’ and persisted through M1 before falling to approximately 75% above baseline by Y2. Conclusion: Ab kinetics after standard smallpox vaccination differ by specific Ab and by previous vaccination status. Anti-A27L and -A33R Ab responses are robust in naïve vaccinees but substantially decay and are only modestly boosted by re-vaccination. The anti-B5R Ab response is modest in naïve vaccinees but persists with little decay and is markedly boosted by re-vaccination. Immune responses to A27L and A33R may be associated with early immunity while B5R Ab may be important for memory immune response.
    Infectious Diseases Society of America 2005 Annual Meeting; 10/2005