Biomedical subjects

Lihan Yan

Publications and source records attributed to Lihan Yan.

11 recordsLinked to original sources

PubMed2006

Safety, immunogenicity and efficacy of modified vaccinia Ankara (MVA) against Dryvax challenge in vaccinia-naïve and vaccinia-immune individuals.

Modified vaccinia Ankara (MVA) was evaluated as an alternative to Dryvax in vaccinia-naïve and vaccinia-immune adult volunteers. Subjects received intramuscular MVA or placebo followed by Dryvax challenge at 3 months. Two or more doses of MVA prior to Dryvax reduced severity of lesion formation, decreased magnitude and duration of viral shedding, and augmented post-Dryvax vaccinia-specific CD8(+) T cell responses and extracellular enveloped virus protein-specific antibody responses. MVA vaccination is safe and immunogenic and improves the safety and immunogenicity of subsequent Dryvax vaccination supporting the potential for using MVA as a vaccine in the general population to improve immunity to orthopoxviruses.

Adolescent↗

PubMed2006

Optimal bandaging of smallpox vaccination sites to decrease the potential for secondary vaccinia transmission without impairing lesion healing.

OBJECTIVE: To assess the optimal method for covering smallpox vaccination sites to prevent transmission of vaccinia. DESIGN: Randomized, nonblinded clinical trial. SETTING: Tertiary care medical center. PARTICIPANTS: Vaccinia-naive and vaccinia-experienced volunteers. INTERVENTIONS: After vaccination, study participants were randomized to receive 1 of 3 types of bandage: gauze, occlusive with gauze lining, or foam. Vaccination sites were assessed every 3 to 5 days until the lesion healed. During each visit, specimens were obtained from the vaccination site, the bandage surface before removal, and the index finger contralateral to the vaccination site and were cultured for vaccinia. Time to lesion healing was assessed. RESULTS: All 48 vaccinia-naive and 47 (87%) of 54 vaccinia-experienced participants developed a vesicle or pustule at the injection site 6-11 days after vaccination. Fourteen (14%) of 102 participants had bandage cultures positive for vaccinia. All but 1 of these vaccinia-positive cultures were of a bandage from participants randomized to the gauze bandage group, and all but 3 were of bandages from vaccinia-naive participants. No finger-specimen cultures were positive for vaccinia. One episode of neck autoinoculation occurred in a vaccinia-naive individual who had vaccinia recovered from his gauze bandage on multiple visits. The foam bandage was associated with more local adverse effects (skin irritation and induration). The time to healing did not differ among the bandage groups. CONCLUSIONS: The potential for transmission of vaccinia from a vaccination site is greater if the site is covered by gauze than if it is covered by occlusive or foam bandages. Use of an occlusive bandage with a gauze lining is the best choice for coverage of smallpox vaccination sites because of a reduced potential for vaccinia transmission and a lower reactogenicity rate. Bandage choice did not affect vaccination lesion healing.

Adult↗

PubMed2006

A phase 1 study of 4 live, recombinant human cytomegalovirus Towne/Toledo chimeric vaccines.

BACKGROUND: Human cytomegalovirus (HCMV) infection acquired in utero often results in severe consequences, including mental retardation and deafness. Although not evaluated for this indication, live attenuated HCMV vaccines based on the Towne strain are well-tolerated and have demonstrated moderate efficacy in other clinical settings. METHODS: To produce live HCMV vaccine candidates that retain the excellent safety profile of the Towne strain but are more immunogenic, the genomes of the Towne strain and the unattenuated HCMV Toledo strain were recombined to yield 4 independent chimeric vaccine candidates. These vaccine candidates were evaluated in 20 HCMV-seropositive persons, in a phase 1, double-blinded, placebo-controlled trial. Participants received a single dose of vaccine or placebo, and the safety and tolerability of the vaccine candidates were evaluated. RESULTS: There was no difference in systemic symptoms between the vaccine and placebo recipients. As a group, vaccine recipients experienced more injection-site reactions than did placebo recipients; however, these were generally minor and short-lived. Vaccine virus could not be detected in blood, urine, or saliva samples obtained from any vaccine recipient. CONCLUSIONS: The Towne/Toledo chimeric vaccine candidates were well tolerated and did not cause systemic infection. Additional human trials are warranted to further evaluate the potential of these vaccine candidates as live virus vaccines.

Adult↗

PubMed2004

Induction of human T cell-mediated immune responses after primary and secondary smallpox vaccination.

BACKGROUND: Postexposure vaccination strategies rely on a rapid induction of poxvirus-specific immune responses. Postvaccination cell-mediated immune (CMI) responses have not been compared by use of controlled trials in previously vaccinated (vaccinia-nonnaive) and nonvaccinated (vaccinia-naive) individuals. METHODS: To assess the time course of vaccinia-specific CMI responses, 20 previously vaccinated and 10 vaccinia-naive individuals were vaccinated with Dryvax, and serial blood samples were drawn. RESULTS: Both groups developed peak levels of vaccinia-specific interferon (IFN)- gamma -producing T cells by day 14 after vaccination. In vaccinia-nonnaive individuals, vaccinia-specific CMI responses were detected by day 7 after vaccination and preceded the increase in antibody titers. IFN- gamma enzyme-linked immunospot responses were significantly different between the 2 groups on days 7 (greater in vaccinia-nonnaive than in vaccinia-naive individuals) and 14 (greater in vaccinia-naive than in vaccinia-nonnaive individuals). Lymphoproliferation responses in vaccinia-nonnaive individuals were significantly higher on days 3 and 7, but cytotoxic T cell lysis activity was not statistically different at any time point. Antibody responses conformed to expected primary and secondary patterns of induction. CONCLUSIONS: This study demonstrates that the kinetics of CMI responses are different after primary vaccination versus after revaccination and indicates that memory can exist in individuals vaccinated >/=30 years ago. These data support the epidemiological observation in smallpox outbreaks that successful revaccination within 4 days of exposure is partially protective. In vaccinia-nonnaive individuals, protection against smallpox during the postexposure revaccination period may require T cell memory as an essential component for the rapid induction of protective cellular and humoral responses.

Adult↗

PubMed2004

Dose-dependent neutralizing-antibody responses to vaccinia.

To evaluate the humoral immune responses to smallpox-vaccine stocks currently available in the United States (Dryvax; Wyeth) and to generate data for comparison of responses to newly produced lots of smallpox vaccine, we evaluated dose-response effects, using undiluted and diluted smallpox vaccine. At 28 and 56 days after vaccination, serum samples were obtained from vaccinated subjects (N=674) who had participated in a randomized, single-blinded trial of an undiluted or a 1 : 5 or 1 : 10 dilution of smallpox vaccine and who subsequently were tested for plaque-reduction neutralizing-antibody titer. All subjects who developed a vesicle after vaccination also developed neutralizing antibodies by day 28. Subjects given either a 1 : 5 or 1 : 10 dilution of vaccinia had significantly higher neutralizing-antibody titers than did subjects given undiluted vaccine. Larger lesion size and fever after vaccination were associated with significantly higher neutralizing-antibody titers after vaccination.

Adolescent↗

PubMed2003

Response to smallpox vaccine in persons immunized in the distant past.

CONTEXT: There is renewed interest in use of smallpox vaccine due to the potential for a bioterrorist attack. This would involve vaccinating health care workers who were previously vaccinated. OBJECTIVE: To evaluate the use of diluted vaccinia virus in vaccination of previously vaccinated (non-naive) participants. DESIGN, SETTING, AND PARTICIPANTS: Eighty non-naive participants, aged 32 to 60 years, were randomized in a single-blinded study to receive either undiluted or diluted (1:3.2, 1:10, or 1:32) doses of smallpox vaccine. A comparison group, aged 18 to 31 years, of 10 vaccinia-naive participants received undiluted vaccine. Participants were enrolled between April 1 and May 15, 2002, at the National Institute of Allergy and Infectious Diseases Vaccine and Treatment Evaluation Unit at Saint Louis University, St Louis, Mo. INTERVENTION: Smallpox vaccine was administered by scarification using 15 skin punctures in the deltoid region of the arm. MAIN OUTCOME MEASURES: Presence of a major reaction, defined as a vesicular or pustular lesion or area of palpable induration surrounding a central lesion following vaccination, and measures of viral shedding and antibody titers. RESULTS: Initial vaccination resulted in a major reaction in 64 of 80 non-naive participants. Ninety-five percent of non-naive participants had major reactions in the undiluted group, 90% in the 1:3.2 dilution group, 81% in the 1:10 dilution group, and 52.6% in the 1:32 dilution group. All (n = 10) of the vaccinia-naive participants had major reactions. Compared with vaccinia-naive participants, non-naive participants had significantly smaller skin lesions (P =.04) and significantly less incidence of fever (P =.02). Preexisting antibody was present in 76 of 80 non-naive participants. Antibody responses were significantly higher and occurred more rapidly in the non-naive participants compared with the vaccinia-naive participants (P =.002 for day 28 and P =.003 for 6 months). Vaccinia-naive participants shed virus from the vaccination site 2 to 6 days longer and had significantly higher peak mean viral titers when compared with the non-naive participants (P =.002). CONCLUSIONS: Previously vaccinated persons can be successfully revaccinated with diluted (<or=1:10) smallpox vaccine. Fewer adverse reactions were observed in this study of non-naive participants when compared with events in vaccinia-naive participants, which may be due to immunologic memory.

Adult↗

PubMed2003

Stability of undiluted and diluted vaccinia-virus vaccine, Dryvax.

The stability of Dryvax vaccine was examined to determine whether diluted vaccine could be used over an extended period, thereby increasing the number of available doses. Stability parameters that we evaluated include dilution (undiluted, diluted 1:5, and diluted 1:10), diluent (original Dryvax diluent, new Dryvax diluent, and phosphate-buffered saline), and temperature (refrigerator temperature and room temperature). Storage of reconstituted Dryvax vaccine at room temperature, regardless of dilution or diluent, resulted in a significantly greater decrease in titer than did storage at refrigerator temperature. At refrigerator temperature, the decrease in vaccinia-vaccine titer during the first year was not significantly different between the undiluted Dryvax vaccine and either of the 2 diluted forms of Dryvax vaccine, with any of the 3 diluents.

Drug Stability↗

PubMed2003

Effect of yearly vaccinations with live, attenuated, cold-adapted, trivalent, intranasal influenza vaccines on antibody responses in children.

BACKGROUND: The cold-adapted, trivalent influenza vaccine (CAIV-T) may become an option for annual vaccination. However, there is little information regarding the immune response to repeated immunization with CAIV-T. OBJECTIVE: To determine the antibody response to repeated immunization with CAIV-T and to compare this with the response after the first CAIV-T immunization. DESIGN AND METHODS: Healthy children were offered CAIV-T immunization for 4 consecutive years, and blood samples were taken from a subset in Years 1, 2 and 4. In Year 4, 156 similarly aged children who had not received influenza vaccine previously were immunized with the same CAIV-T. RESULTS: The H3N2 and B components of the CAIV-T induced high antibody titers in Year 1 that were maintained during 4 years. The H1N1 titers were lower than the H3N2 or B titers. Comparison of the group immunized for 4 consecutive years with the group immunized for the first time revealed the following: (1) before immunization yearly immunized subjects were more likely to be seropositive to each of the three vaccine strains than those immunized for the first time (P < 0.05 for each); (2) after immunization the percentage of seropositive subjects to each of the strains was similar; (3) after immunization titers were higher in the subjects immunized for the first time than those immunized yearly (P < 0.05 for H3N2 and B). CONCLUSION: Yearly vaccination with CAIV-T induced high antibody titers, especially to the H3N2 and B strains in the vaccines. The titers in those immunized with CAIV-T for the first time were higher than in those immunized for 4 consecutive years.

Administration, Intranasal↗

PubMed2003

Improved assay to detect neutralizing antibody following vaccination with diluted or undiluted vaccinia (Dryvax) vaccine.

The assessment of immunogenicity of a diluted vaccinia vaccine for possible widespread use of a diluted vaccine in the event of a bioterrorist attack prompted us to focus on the development of a sensitive and specific plaque reduction neutralization (PRN) assay to assess the antibody response of volunteers to a vaccinia (Dryvax) vaccine. Two incubation times, 1 h or overnight (approximately 15 h), were explored for the neutralization step of the assay. In addition, serum samples were evaluated using both sonicated and nonsonicated virus in PRN assays with 1 and 15 h of incubation. The use of the overnight incubation method resulted in the detection of antibody in two vaccinated individuals who exhibited a take, i.e., a major reaction indicative of successive vaccination as defined by the Centers for Disease Control and Prevention, but did not have a fourfold increase in antibody to vaccinia virus by the 1-h-incubation method and increased the sensitivity from 94 to 100%. In addition to the increased sensitivity of the assay, we noted a significant increase (approximately 40-fold) in the PRN titer of serum samples tested with the 15-h-incubation method. The use of sonicated virus increased the reproducibility of the virus titers and PRN titers. Forty-two percent of the samples tested using sonicated virus had a PRN titer that was fourfold higher or greater than that of nonsonicated virus in the assay. A PRN titer that was threefold higher or greater was observed in more than half (58%) of the samples using sonicated virus. Therefore, the more sensitive, specific, and reproducible plaque neutralization assay for the detection of antibody to vaccinia virus is the method using a 15-h-incubation time and freshly sonicated vaccinia virus.

Antibodies, Viral↗

PubMed2002

Relationship of AcrySof acrylic and PhacoFlex silicone intraocular lenses to visual acuity and posterior capsule opacification.

PURPOSE: To compare the changes in visual acuity and the development of posterior capsule opacification (PCO) with AcrySof acrylic intraocular lenses (IOLs) (Alcon Laboratories) and second-generation PhacoFlex silicone IOLs (Allergan ). SETTING: Eye Associates of New Mexico and Southwest Colorado, Albuquerque, New Mexico, USA. METHODS: Medical charts of patients having cataract extraction with implantation of an AcrySof MA30BA or MA60BM (MA30/60) or PhacoFlex SI-30NB or SI-40NB (SI-30/40) IOL between January 1995 and June 1997 were abstracted. Analyzed were the changes in visual acuity and development of PCO 1 month postoperatively and at the last available ophthalmologist visit or the visit before neodymium:YAG (Nd:YAG) capsulotomy. RESULTS: Patients with MA30/60 acrylic IOLs were significantly older, had a worse preoperative best corrected visual acuity (BCVA), and had more concomitant ocular diseases than those with SI-30/40 silicone IOLs. The change in BCVA from preoperatively to 1 month postoperatively was equivalent in the 2 lens groups. The BCVA declined from 1 month postoperatively to the last recorded or pre-Nd:YAG visit. This decline was greater in eyes with SI-30/40 silicone IOLs than in those with MA30/60 acrylic IOLs. Although the decrease in BCVA between IOL types was not significantly different, eyes with a SI-30/40 silicone IOL were significantly more likely to develop PCO and have Nd:YAG capsulotomy. Eyes developing PCO had a statistically significant decline in BCVA from 1 month postoperatively to the last/pre-Nd:YAG visit. CONCLUSIONS: The MA30/60 acrylic lenses were associated with lower PCO and Nd:YAG capsulotomy rates than second-generation SI-30/40 silicone IOLs. Patients with MA30/60 IOLs also tended to have less of a decrease in visual acuity than patients with SI-30/40 silicone lenses, probably as a result of the difference in PCO rates between groups.

Acrylic Resins↗

PubMed2002

Safety of the trivalent, cold-adapted influenza vaccine in preschool-aged children.

OBJECTIVE: To provide additional information on the safety of trivalent, cold-adapted influenza vaccine (CAIV-T) in children. METHODS: Children 15 to 71 months of age were enrolled in a multicenter, prospective, randomized, double-blind, and placebo-controlled trial to receive by nasal spray CAIV-T or placebo. In year 1 (1996-1997), 1314 were enrolled in the 2-dose cohort and 288 were enrolled in the 1-dose cohort. In year 2 (1997-1998), 1358 of the original participants received 1 dose of vaccine or placebo according to their original treatment group assignment. In year 3 (1998-1999) and year 4, the trial continued as an open-label safety trial of CAIV-T. A total of 642 and 549 children enrolled in years 3 and 4, respectively, received their third and fourth sequential annual doses of CAIV-T. Measured were 1) the occurrence of specific respiratory, gastrointestinal and systemic symptoms, unexpected symptoms (not specified in the diary card), and use of medications within the first 10 days after vaccination; 2) the occurrence of an acute illness and use of medication within 11 to 42 days after vaccination; and 3) the occurrence of serious adverse events within 42 days after vaccination. RESULTS: The adjusted odd ratios of specific respiratory and gastrointestinal symptoms during the 10 days after vaccination were determined in years 1 and 2. Runny nose or nasal congestion, vomiting, muscle aches, and fever were significantly associated with the first dose of CAIV-T. With the second dose, runny nose was the only symptom that was associated with CAIV-T. In year 2, CAIV-T did not cause excess in any of the specific respiratory and gastrointestinal symptoms. In years 3 and 4, specific respiratory and gastrointestinal symptoms were comparable to that observed in year 2. A CAIV-T-associated symptom was most likely to occur on day 2 with the first dose of vaccine. The occurrence of unexpected symptoms was primarily of the gastrointestinal system. Approximately 6% of CAIV-T and 3.6% of placebo recipients had a gastrointestinal symptom. CAIV-T seemed to be associated with a mild excess in abdominal pain and vomiting only with the first vaccine dose. A statistically significant increase in the use of analgesics/antipyretics was detected only with the first dose in CAIV-T vaccinees compared with placebo recipients (23.5% vs 16.6%). Between days 11 and 42, CAIV-T use was not associated with an excess of illness, otitis media, or use of medication. None of the 6 serious adverse events in CAIV-T recipients in years 1 to 4 was attributed to the vaccine. CONCLUSIONS: CAIV-T was safe in children. Mild respiratory, gastrointestinal, and systemic symptoms of short duration were observed in a minority of children and primarily with the first vaccine dose. Sequential annual doses of CAIV-T were well tolerated.

Age Factors↗