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• MAS-1 adjuvant with 9 µg per hemagglutinin in 0.3 mL was safe and immunogenic in the elderly. • Antibodies to adjuvanted vaccine peaked by 85 days and were durable at 169 days. • Responses to adjuvanted vaccine appeared better than high dose influenza vaccine. • Adjuvanted vaccine induced seroresponses to non-study vaccine strains. • Late injection site reactions occurred with adjuvanted vaccine 0.5 mL dose volume. Increased influenza vaccine efficacy is needed in the elderly at high-risk for morbidity and mortality due to influenza infection. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. A phase 1, randomized, double-blind, safety and immunogenicity, adjuvant dose escalation trial was conducted in persons aged 65 years and older. MAS-1 adjuvant dose volumes at 0.3 mL or 0.5 mL containing 9 µg per HA derived from licensed seasonal trivalent influenza vaccine (IIV, Fluzone HD 60 µg per HA, Sanofi Pasteur) were compared to high dose (HD) IIV (Fluzone HD). Safety was measured by reactogenicity, adverse events, and safety laboratory measures. Immunogenicity was assessed by serum hemagglutination inhibition (HAI) antibody titers. Forty-five subjects, aged 65–83 years, were randomly assigned to receive 9 µg per HA in 0.3 mL MAS-1 (15 subjects) or HD IIV (15 subjects) followed by groups randomly assigned to receive 9 µg per HA in 0.5 mL MAS-1 (10 subjects) or HD IIV (5 subjects). Injection site tenderness, induration, and pain, and headache, myalgia, malaise and fatigue were common, resolving before day 14 post-vaccination. Clinically significant late-onset injection site reactions occurred in four of ten subjects at the 0.5 mL adjuvant dose. Safety laboratory measures were within acceptable limits. MAS-1-adjuvanted IIV enhanced mean antibody titers, mean-fold increases in antibody titer, and seroconversion rates against vaccine strains for at least 168 days post-vaccination and enhanced cross-reactive antibodies against some non-study vaccine influenza viruses. MAS-1 adjuvant provided HA dose-sparing without safety concerns at the 0.3 mL dose, but the 0.5 mL dose caused late injection site reactions. MAS-1-adjuvanted IIV induced higher HAI antibody responses with prolonged durability including against historical strains, thereby providing greater potential vaccine efficacy in the elderly throughout an influenza season. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680. [ABSTRACT FROM AUTHOR]

Background: The association of hemagglutination inhibition (HAI) antibodies with protection from influenza among healthcare personnel (HCP) with occupational exposure to influenza viruses has not been well-described.Methods: The Respiratory Protection Effectiveness Clinical Trial was a cluster-randomized, multisite study that compared medical masks to N95 respirators in preventing viral respiratory infections among HCP in outpatient healthcare settings for 5180 participant-seasons. Serum HAI antibody titers before each influenza season and influenza virus infection confirmed by polymerase chain reaction were studied over 4 study years.Results: In univariate models, the risk of influenza A(H3N2) and B virus infections was associated with HAI titers to each virus, study year, and site. HAI titers were strongly associated with vaccination. Within multivariate models, each log base 2 increase in titer was associated with 15%, 26% and 33%-35% reductions in the hazard of influenza A(H3N2), A(H1N1), and B infections, respectively. Best models included preseason antibody titers and study year, but not other variables.Conclusions: HAI titers were associated with protection from influenza among HCP with routine exposure to patients with respiratory illness and influenza season contributed to risk. HCP can be reassured about receiving influenza vaccination to stimulate immunity. [ABSTRACT FROM AUTHOR]

• MAS-1 water-in-oil adjuvant with reduced doses of hemagglutinin (HA) was evaluated. • HA + MAS-1 was safe and more immunogenic than standard dose unadjuvanted vaccine. • Antibody responses were maintained up to 6 months with adjuvanted vaccine. • Antibodies to some non-study vaccine strains were higher in adjuvanted vaccine groups. • MAS-1 adjuvant offered HA dose-sparing effects and durable immunity in young adults. New influenza vaccines are needed to increase vaccine efficacy. Adjuvants may allow hemagglutinin (HA) dose-sparing with enhanced immunogenicity. MAS-1 is an investigational low viscosity, free-flowing, water-in-oil emulsion-based adjuvant/delivery system comprised of stable nanoglobular aqueous droplets. A phase 1, double-blind, safety and immunogenicity, HA dose escalation, randomized clinical trial was conducted. MAS-1 adjuvant with 1, 3, 5 or 9 µg per HA derived from licensed seasonal trivalent high dose inactivated influenza vaccine (IIV, Fluzone HD 60 µg per HA) in a 0.3 mL dose were compared to standard dose IIV (Fluzone SD, 15 µg per HA). Safety was measured by reactogenicity, adverse events, and clinical laboratory tests. Serum hemagglutination inhibition (HAI) antibody titers were measured for immunogenicity. Seventy-two subjects, aged 18–47 years, received one dose of either 0.3 mL adjuvanted vaccine or SD IIV intramuscularly. Common injection site and systemic reactions post-vaccination were mild tenderness, induration, pain, headache, myalgia, malaise and fatigue. All reactions resolved within 14 days post-vaccination. Safety laboratory measures were not different between groups. Geometric mean antibody titers, geometric mean fold increases in antibody titer, seroconversion rates and seroprotection rates against vaccine strains were in general higher and of longer duration (day 85 and 169 visits) with MAS-1-adjuvanted IIV at all doses of HA compared with SD IIV. Adjuvanted vaccine induced higher antibody responses against a limited number of non-study vaccine influenza B and A/H3N2 viruses including ones from subsequent years. MAS-1 adjuvant in a 0.3 mL dose volume provided HA dose-sparing effects without safety concerns and induced higher HAI antibody and seroconversion responses through at least 6 months, demonstrating potential to provide greater vaccine efficacy throughout an influenza season in younger adults. In summary, MAS-1 may provide enhanced, more durable and broader protective immunity compared with non-adjuvanted SD IIV. Clinical Trial Registry: ClinicalTrials.gov # NCT02500680. [ABSTRACT FROM AUTHOR]

Background An intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone ® Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18–64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety. Methods This randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18–64 years of age in the US during the 2012–2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination. Results 1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction. Conclusions Antibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines. [ABSTRACT FROM AUTHOR]

Highlights: [•] The ID and HD vaccines were more immunogenic than standard IM vaccine in older adults. [•] The ID and HD vaccines were well-tolerated in older adults. [•] The HD vaccine was more immunogenic than the ID vaccines in older adults. [•] HD vaccine in older adults was comparable to standard vaccine in younger adults. [•] HD and ID vaccines both offer suitable vaccination strategies for older adults. [ABSTRACT FROM AUTHOR]

Highlights: [•] Revaccination with intradermal (ID) influenza vaccine was immunogenic and safe. [•] Previous vaccination with ID vaccine had no impact on intramuscular (IM) vaccination. [•] Injection site reactions were more frequent with ID vaccine but were well-tolerated. [•] Safety was more closely linked to the current injection route than the previous route. [•] Immunogenicity was similar for the ID and IM vaccine groups for all virus strains. [Copyright &y& Elsevier]

Highlights: [•] We compared reduced dose intradermal (ID) to standard dose intramuscular (IM) influenza vaccine. [•] Three lots of ID vaccine were comparable to each other. [•] The immunogenicity of the two vaccines was comparable. [•] Injection site reactions were more frequent with the ID vaccine except pain. [•] Systemic reactions were comparable except for more myalgia with IM vaccine. [ABSTRACT FROM AUTHOR]

Summary: We evaluated EP HIV-1090 vaccine, a DNA plasmid encoding 21 cytotoxic T-lymphocyte (CTL) epitopes of human immunodeficiency virus type 1 (HIV-1) and the pan-DR helper T-lymphocyte epitope (PADRE), in a dose escalation, randomized, double-blinded, placebo-controlled Phase 1 trial. Vaccine, at 0.5, 2.0, or 4.0mg doses, or placebo was injected four times over 6 months. Forty-two healthy, HIV-1-uninfected adults were enrolled. Using an interferon-γ ELISPOT assay, a response to PADRE was detected in one vaccine recipient. Three vaccine recipients raised anti-HIV-1 CD8+ CTL measured by chromium-release assay. The vaccine was safe and well-tolerated, but only weakly immunogenic. [Copyright &y& Elsevier]

The article presents a study on the effects of an influenza season on patients with Chronic Obstructive Pulmonary Disease COPD. The study was analyzed through spirometry to assess functional status and well-being and tested for influenza virus infection. The study reveals that the acute respiratory illness was associated with increased health care utilization and obstruction to airflow that form into a worse functional status and well-being of the patients.

Summary: Background: We report the results of a phase I dose escalation, safety and immunogenicity trial of a new recombinant protective antigen (rPA102) anthrax vaccine. Methods: Hundred healthy volunteers were randomized in a 4:1 ratio to receive intramuscular doses of rPA102 in the following formulations: 5, 25, 50, or 75μg of rPA102 in 82.5μg aluminum hydroxide adjuvant at 0, 4, and 8 weeks; or the US licensed Anthrax Vaccine Adsorbed (AVA) at weeks 0 and 4. Findings: Local reactogenicity (mostly pain) was more common with AVA than with rPA102 following the first (94.7% versus 44.4%; p <0.001) and the second (84.2% versus 35.4%; p <0.001) vaccinations. Systemic reactogenicity (mostly headache) was more common among rPA102 vaccinees, but only following the first vaccination (49.4% versus 15.8%; p =0.025). A dose-response relationship for anti-PA antibodies was present after the 2nd and 3rd vaccinations. Two weeks following the 2nd vaccination, the geometric mean titers (GMT) for lethal toxin neutralization activity (TNA), for the 5, 25, 50 and 75μg rPA102 and AVA groups were 38.6, 75.4, 373.9, 515.3, and 855.2, respectively. The geometric mean concentrations (GMC) measured by anti-PA IgG ELISA were 3.7, 11.5, 25.9, 44.1, and 171.6, respectively. Two weeks following the 3rd vaccination, TNA GMTs for the four rPA102 groups, were: 134.7, 719.7, 2116.6, 2422.4; and ELISA GMCs were: 22.9, 104.7, 196.4, and 262.6, respectively. Interpretation: No clinically serious or dose-related toxicity or reactogenicity was observed. The TNA response after two injections of the 75μg dose of rPA102 was similar to the response after two injections of AVA. The third rPA102 vaccination substantially increased the antibody response. [Copyright &y& Elsevier]

Background. Chronically ill older adults constitute a population vulnerable for complications associated with influenza. Study of their immunity to influenza virus may help design better strategies to stimulate protective immune responses. Methods. Immunogenicity of influenza vaccines and immune protection from natural influenza were assessed in older adults with chronic obstructive pulmonary disease as part of a vaccine efficacy trial. Subjects received either trivalent inactivated influenza virus vaccine (TVV) intramuscularly and trivalent live cold-adapted influenza virus vaccine (CAIV-T; n = 1107) intranasally (inl) or TVV and placebo inl (P; n = 1108). Results. In the subsets of study subjects assessed, serum hemagglutination inhibition (HAI) and nasal-wash antihemagglutinin (HA) immunoglobulin (Ig) A and IgG antibody levels and anti-influenza virus CD8+ cytotoxic T lymphocyte activity increased after immunization. Mean postimmunization nasal-wash IgA antibody levels to influenza A H3/HA and B HA were statistically higher in the group (n = 957 ) than in the TVV+CAIV-T group ( n = 951). Postimmunization serum HAI and nasal-wash IgA antibodies to influenza A/H3N2 TVV+P and B viruses were associated with a reduced relative risk for natural influenza infection. Conclusions. appeared more immunogenic than , but the observed difference may TVV+CAIV-T TVV+P be clinically unimportant. Anti-influenza serum and nasal-wash antibodies were associated with immuneprotection. [ABSTRACT FROM AUTHOR]

Binding of antibodies to oligomeric envelope glycoprotein of R5-tropic primary isolates of human immunodeficiency virus type 1 (HIV-1) was studied by flow cytometry using sera from HIV-1 vaccine recipients and clade B and C HIV-1-infected patients, and monoclonal and polyclonal antibodies to neutralizing epitopes of HIV-1. Vaccine recipients received recombinant canarypox virus vaccine expressing HIV-1 gene products, and SF-2 recombinant gp120 subunit vaccine. Anti-gp120 neutralizing antibodies including human monoclonal antibody 2G12 and goat polyclonal anti-serum to V3 loop peptide [peptide T1-SP10MN(A)] bound to HIV-1-infected cells. Sera from vaccine recipients bound to HIV-1-infected cells, but at levels lower than did infected patient sera. [Copyright &y& Elsevier]

We assessed whether trivalent live, cold-adapted influenza virus (CAIV-T) vaccine provides added protection when co-administered with trivalent inactivated influenza virus vaccine (TVV) in patients with chronic obstructive pulmonary disease (COPD). Subjects (N=2215) were randomly assigned to receive either TVV intramuscularly (IM) and CAIV-T intranasally (TC), or TVV and placebo (TP). The vaccines were well-tolerated. Efficacy of TC compared to TP was not statistically significant and was 0.16 for any influenza virus strain (95% confidence limit (CL): −0.22, 0.43), 0.26 for A (H3N2) virus (95% CL: −0.17, 0.53), and −0.05 for type B virus (95% CL: −1.13, 0.48). However, there was a possible advantage for TC over TP in reducing respiratory consequences of an influenza season measured by pulmonary function and symptoms at end of study. [Copyright &y& Elsevier]

Induction of human γδ T cells was investigated in subjects who were vaccinated with live recombinant canarypox virus expressing human immunodeficiency virus (HIV) proteins or soluble MN rgp120. Both canarypox and rgp120 induced antigen-specific lymphoproliferative and interferon (IFN)—γ responses. However, only canarypox vaccination induced increased γδ T cell responses detectable after secondary in vitro expansion (P < .02). These enhanced γδ T cell responses were specific for canarypox but not HIV antigens. Canarypox-specific γδ T cells were predominantly Vγ9[sub +] and produced intracellular and secreted IFN-γ. γδ T cell lines generated from canarypox vaccinees responded to canarypox antigens but not to mycobacterial antigens shown previously to induce bacille Calmette-Guérin—specific γδ T cells. Furthermore, canarypox vaccinations were associated with significantly higher NK cell expansions (P = .02). Increased IFN—γ production by γδ T and NK cells could enhance the induction of protective type 1 memory immunity. Thus, stimulation of γδ T cells might be an important feature of live vaccines. [ABSTRACT FROM AUTHOR]

Examines the effectiveness of an antiviral vaccine on pregnant HIV-positive women. Measurement of CD4 lymphocyte counts; Absence of significant local or systemic reactions; Reasons why the vaccination did not alter plasma RNA reverse transcriptase-polymerase chain reaction copy number.

Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a large risk to healthcare personnel (HCP). Quantifying the risk of coronavirus infection associated with workplace activities is an urgent need. Methods We assessed the association of worker characteristics, occupational roles and behaviors, and participation in procedures with the risk of endemic coronavirus infection among HCP who participated in the Respiratory Protection Effectiveness Clinical Trial (ResPECT), a cluster randomized trial to assess personal protective equipment to prevent respiratory infections and illness conducted from 2011 to 2016. Results Among 4689 HCP seasons, we detected coronavirus infection in 387 (8%). HCP who participated in an aerosol-generating procedure (AGP) at least once during the viral respiratory season were 105% (95% confidence interval, 21%–240%) more likely to be diagnosed with a laboratory-confirmed coronavirus infection. Younger individuals, those who saw pediatric patients, and those with household members <5 years of age were at increased risk of coronavirus infection. Conclusions Our analysis suggests that the risk of HCP becoming infected with an endemic coronavirus increases approximately 2-fold with exposures to AGPs. Our findings may be relevant to the coronavirus disease 2019 (COVID-19) pandemic; however, SARS-CoV-2, the virus that causes COVID-19, may differ from endemic coronaviruses in important ways. Clinical Trials Registration NCT01249625. [ABSTRACT FROM AUTHOR]

Background: Study of human coronavirus and other virus-associated respiratory illnesses is needed to describe their clinical effects on chronically ill, older adults.Methods: A prospective study during 2009 to 2013 clinically assessed acute respiratory illnesses soon after onset and 3 to 4 weeks later in patients aged ≥60 years with chronic lung and heart diseases (group 1, 100 subjects) and healthy adults aged 18 to 40 years (group 2, 101 subjects). Respiratory secretions were tested for nucleic acids of a panel of respiratory viruses. An increase in antibody titer was assessed for 4 coronavirus strains.Results: Virus-associated illnesses (29 [39.1%] of 74 illnesses in group 1 and 59 [48.7%] of 121 illnesses in group 2) occurred in all calendar quarters, most commonly in the first and fourth quarters. Coronaviruses (group 1: 14 [18.9%] illnesses; group 2: 26 [21.5%] illnesses) and enteroviruses/rhinoviruses (group 1: 14 [18.9%] illnesses; group 2: 37 [30.6%] illnesses) were most common. Virus co-infections occurred in 10 illnesses. Illnesses with 9 to 11 symptoms were more common in group 1 (17 [23.0%]) than in group 2 (15 [12.4%]) (P < .05). Compared with group 2, more group 1 subjects reported dyspnea, more severe disease of longer duration, and treatment for acute illness with prednisone and antibiotics. Coronavirus-associated illnesses (percent of illnesses, group 1 vs group 2) were characterized by myalgias (21% vs 68%, P < .01), chills (50% vs 52%), dyspnea (71% vs 24%, P < .01), headache (64% vs 72%), malaise (64% vs 84%), cough (86% vs 68%), sputum production (86% vs 60%), sore throat (64% vs 80%), and nasal congestion (93% vs 96%).Conclusions: Respiratory illnesses were commonly associated with coronaviruses and enteroviruses/rhinoviruses affecting chronically ill, older patients more than healthy, young adults. [ABSTRACT FROM AUTHOR]

Background Viral respiratory infections (VRIs) are common and are occupational risks for healthcare personnel (HCP). VRIs can also be acquired at home and other settings among HCPs. We sought to determine if preschool-aged household contacts are a risk factor for VRIs among HCPs working in outpatient settings. Methods We conducted a secondary analysis of data from a cluster randomized trial at 7 medical centers in the United States over 4 influenza seasons from 2011–2012 to 2014–2015. Adult HCPs who routinely came within 6 feet of patients with respiratory infections were included. Participants were tested for respiratory viruses whenever symptomatic and at 2 random times each season when asymptomatic. The exposure of interest was the number of household contacts 0–5 years old (preschool-aged) at the beginning of each HCP-season. The primary outcome was the rate of polymerase chain reaction–detected VRIs, regardless of symptoms. The VRI incidence rate ratio (IRR) was calculated using a mixed-effects Poisson regression model that accounted for clustering at the clinic level. Results Among the 4476 HCP-seasons, most HCPs were female (85.4%) and between 30 and 49 years of age (54.6%). The overall VRI rate was 2.04 per 100 person-weeks. In the adjusted analysis, HCPs having 1 (IRR, 1.22 [95% confidence interval {CI}, 1.05–1.43]) and ≥2 (IRR, 1.35 [95% CI, 1.09–1.67]) preschool-aged household contacts had higher VRI rates than those with zero preschool-aged household contacts. Conclusions Preschool-aged household contacts are a risk factor for developing VRIs among HCPs working in outpatient settings. [ABSTRACT FROM AUTHOR]

Describes the recruitment and baseline epidemiologic characteristics of volunteers in the first phase 3 placebo-controlled trial of recombinant gp120 HIV vaccine. Medical history of participants in the study; Recruitment strategies; Demographics; Risk factors; Determination of HIV status by standard HIV-1 antibody assays; HIV-1 nucleic acid test conducted to determine seronegative and viremic HIV infection at enrollment.

A substudy analysis was conducted to determine the clinical characteristics associated with symptomatic, laboratory-documented influenza (LDI) among 2215 veterans with chronic obstructive pulmonary disease who participated in Department of Veterans Affairs Cooperative Study 448 and who received trivalent inactivated influenza virus vaccine with or without intranasal live-attenuated, cold-adapted influenza vaccine. Of 585 evaluable first occurrences of acute respiratory illnesses, 94 (16%) were LDI. Respiratory symptoms of cough, sputum production, and dyspnea occurred in >90% of patients with LDI; 68% had documented or subjective fever, and 81% had myalgias. Stepwise logistic regression identified only fever and myalgia as being statistically associated with LDI. During the influenza outbreak period, the positive predictive value of fever and myalgia was 41%. Clinical criteria were poor predictors of LDI in these older, vaccinated patients with chronic lung disease. Additional studies are warranted to define optimal methods for the diagnosis of influenza among older persons with chronic obstructive pulmonary disease. [ABSTRACT FROM AUTHOR]

Presents a study which examined the safety and immunogenicity of a canarypox vector HIV type 1 vaccine with or without gp120 boosting. Methodology; Results; Discussion.

Importance: Clinical studies have been inconclusive about the effectiveness of N95 respirators and medical masks in preventing health care personnel (HCP) from acquiring workplace viral respiratory infections.Objective: To compare the effect of N95 respirators vs medical masks for prevention of influenza and other viral respiratory infections among HCP.Design, Setting, and Participants: A cluster randomized pragmatic effectiveness study conducted at 137 outpatient study sites at 7 US medical centers between September 2011 and May 2015, with final follow-up in June 2016. Each year for 4 years, during the 12-week period of peak viral respiratory illness, pairs of outpatient sites (clusters) within each center were matched and randomly assigned to the N95 respirator or medical mask groups.Interventions: Overall, 1993 participants in 189 clusters were randomly assigned to wear N95 respirators (2512 HCP-seasons of observation) and 2058 in 191 clusters were randomly assigned to wear medical masks (2668 HCP-seasons) when near patients with respiratory illness.Main Outcomes and Measures: The primary outcome was the incidence of laboratory-confirmed influenza. Secondary outcomes included incidence of acute respiratory illness, laboratory-detected respiratory infections, laboratory-confirmed respiratory illness, and influenzalike illness. Adherence to interventions was assessed.Results: Among 2862 randomized participants (mean [SD] age, 43 [11.5] years; 2369 [82.8%]) women), 2371 completed the study and accounted for 5180 HCP-seasons. There were 207 laboratory-confirmed influenza infection events (8.2% of HCP-seasons) in the N95 respirator group and 193 (7.2% of HCP-seasons) in the medical mask group (difference, 1.0%, [95% CI, -0.5% to 2.5%]; P = .18) (adjusted odds ratio [OR], 1.18 [95% CI, 0.95-1.45]). There were 1556 acute respiratory illness events in the respirator group vs 1711 in the mask group (difference, -21.9 per 1000 HCP-seasons [95% CI, -48.2 to 4.4]; P = .10); 679 laboratory-detected respiratory infections in the respirator group vs 745 in the mask group (difference, -8.9 per 1000 HCP-seasons, [95% CI, -33.3 to 15.4]; P = .47); 371 laboratory-confirmed respiratory illness events in the respirator group vs 417 in the mask group (difference, -8.6 per 1000 HCP-seasons [95% CI, -28.2 to 10.9]; P = .39); and 128 influenzalike illness events in the respirator group vs 166 in the mask group (difference, -11.3 per 1000 HCP-seasons [95% CI, -23.8 to 1.3]; P = .08). In the respirator group, 89.4% of participants reported "always" or "sometimes" wearing their assigned devices vs 90.2% in the mask group.Conclusions and Relevance: Among outpatient health care personnel, N95 respirators vs medical masks as worn by participants in this trial resulted in no significant difference in the incidence of laboratory-confirmed influenza.Trial Registration: ClinicalTrials.gov Identifier: NCT01249625. [ABSTRACT FROM AUTHOR]

Background: Although N95 filtering facepiece respirators and medical masks are commonly used for protection against respiratory infections in healthcare settings, more clinical evidence is needed to understand the optimal settings and exposure circumstances for healthcare personnel to use these devices. A lack of clinically germane research has led to equivocal, and occasionally conflicting, healthcare respiratory protection recommendations from public health organizations, professional societies, and experts.Methods: The Respiratory Protection Effectiveness Clinical Trial (ResPECT) is a prospective comparison of respiratory protective equipment to be conducted at multiple U.S. study sites. Healthcare personnel who work in outpatient settings will be cluster-randomized to wear N95 respirators or medical masks for protection against infections during respiratory virus season. Outcome measures will include laboratory-confirmed viral respiratory infections, acute respiratory illness, and influenza-like illness. Participant exposures to patients, coworkers, and others with symptoms and signs of respiratory infection, both within and beyond the workplace, will be recorded in daily diaries. Adherence to study protocols will be monitored by the study team.Discussion: ResPECT is designed to better understand the extent to which N95s and MMs reduce clinical illness among healthcare personnel. A fully successful study would produce clinically relevant results that help clinician-leaders make reasoned decisions about protection of healthcare personnel against occupationally acquired respiratory infections and prevention of spread within healthcare systems.Trial Registration: The trial is registered at clinicaltrials.gov, number NCT01249625 (11/29/2010). [ABSTRACT FROM AUTHOR]

Background. Influenza-associated morbidity and mortality has not decreased in the last decade, despite increased receipt of vaccine. To improve the immunogenicity of influenza vaccine, a high-dose (HD) trivalent, inactivated influenza vaccine was developed. Methods. A multicenter, randomized, double-blind controlled study was conducted to compare HD vaccine (which contains 60 mg of hemagglutinin per strain) with the licensed standard-dose (SD) vaccine (which contains 15 mg of hemagglutinin per strain) in adults ⩾65 years of age. Results. HD vaccine was administered to 2575 subjects, and SD vaccine was administered to 1262 subjects. There was a statistically significant increase in the rates of seroconversion and mean hemagglutination inhibition titers at day 28 after vaccination among those who received HD vaccine, compared with those who received SD vaccine. Mean postvaccination titers for individuals who received HD vaccine were 116 for H1N1, 609 for H3N2, and 69 for B strain; for those who received SD vaccine, mean postvaccination titers were as 67 for H1N1, 333 for H3N2, and 52 for B strain. The HD vaccine met superiority criteria for both A strains, and the responses for B strain met noninferiority criteria. Seroprotection rates were also higher for those who received HD vaccine than for those who received SD vaccine vaccine, for all strains. Local reactions were more frequent in individuals who received HD vaccine, but the reactions were mild to moderate. Conclusions. There was a statistically significant increase in the level of antibody response induced by HD influenza vaccine, compared with that induced by SD vaccine, without an attendant increase in the rate or severity of clinically relevant adverse reactions. These results suggest that the high-dose vaccine may provide improved protective benefits for older adults. [ABSTRACT FROM AUTHOR]

Background: The clinical features and incidence of human coronavirus (HCoV) infections in chronically ill older adults need better definition.Methods: HCoV infection was determined on the basis of a 4-fold increase in serum antibody and the detection of HCoV by reverse-transcription polymerase chain reaction. Laboratory-documented influenza (LDI) was detected by serologic assay and culture. HCoV illnesses were compared with other acute respiratory illnesses identified by active surveillance, during the 1998-99 winter respiratory-virus season, of 2215 patients with chronic obstructive pulmonary disease who were > or = 50 years old and who received influenza vaccines.Results: HCoV-229E and HCoV-OC43 were associated with 90 (14%) of 665 illnesses (HCoV-229E in 22, HCoV-OC43 in 67, and both in 1), LDI with 107 (16%) of 678 illnesses. In multivariate logistic regression analysis, myalgia was less likely with HCoV infection than with LDI (OR, 0.27 [95% confidence limit, 0.13-0.58]). A majority of these HCoV and LDI illnesses exhibited each of 11 symptoms and signs of acute respiratory illness. Spirometric results worsened most often with LDI, and many acute respiratory illnesses, regardless of etiology, were associated with hospitalization. A total of 8 illnesses were associated with HCoV-NL63, 1 with HCoV-HKU1.Conclusions: The frequencies of HCoV and LDI illnesses were similar. HCoV illness was less severe than LDI illness, was accompanied by multiple respiratory and systemic symptoms, and was associated with hospitalization. [ABSTRACT FROM AUTHOR]

Background. Respiratory syncytial virus (RSV) has been recognized recently as an important adult pathogen. Methods. This randomized, double-blind, placebo-controlled study was designed to compare humoral responses to licensed trivalent influenza vaccine given concomitantly with 1 of 2 RSV vaccine formulations in persons ⩾65 years old with cardiopulmonary disease. Hemagglutinin-inhibition assays and neutralization assays were used to measure levels of antibody to influenza and RSV, respectively. Subjects with respiratory illnesses during subsequent winters were tested for RSV and influenza by reverse-transcriptase polymerase chain reaction and serologic analysis. Results. Neither RSV vaccine formulation had an effect on the humoral response to influenza vaccination, and both RSV vaccines were well tolerated by 1169 participants. The immunogenicity of the nonadjuvanted vaccine was judged superior on the basis of mean postvaccination neutralizing antibody titers (12.5 vs. 12.1) and the percentage of subjects for whom ⩾4-fold increases in neutralizing titer were observed when acute-phase and convalescent-phase serum samples were compared (168 [44%] of 383 vs. 129 [33%] of 400). In year 1, the percentage of illnesses due to RSV was 7% (36 of 492 illnesses) and that due to influenza was 8%(40 of 492), compared with 6% (11 of 189) due to RSV and 11% (20 of 189) due to influenza in year 2. The incidence of RSV infection was not significantly different in the RSV vaccine and placebo groups. Conclusions. Although the safety and immunogenicity data of these RSV vaccines are encouraging, low rates of infection make it challenging to design efficacy trials. [ABSTRACT FROM AUTHOR]

Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus—based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1—specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen. [ABSTRACT FROM AUTHOR]

Presents a study which described the use of a recombinant canarypox virus vaccine in both high-risk and low-risk persons and evaluated variations in dosing schedule in combination with a recombinant subunit group120 protein. Characteristics of the subjects; Laboratory methods performed in the study; Tolerability with the vaccine.

Reports on the effectiveness of live, attenuated influenza virus (LAIV) vaccines and the economic and medical implications. Objective; Design; Setting; Participants; Intervention; Main outcome measures; Results; Conclusion.

Objective: To evaluate the safety and immunogenicity of a human immunodeficiency virus type 1 (HIV-1) recombinant envelope glycoprotein (rgp 160) candidate vaccine in humans.Subjects: Healthy adults (72) who were seronegative for HIV-1 were randomly assigned to one of four groups.Interventions: The subjects were randomly assigned to receive 40 or 80 micrograms of rgp 160, 10 micrograms of hepatitis B vaccine, or placebo in three doses (on days 0, 30, and 180), with an elective, nonblinded administration of a fourth dose on day 540.Measurements and Main Results: Neither clinical nor laboratory toxicity was encountered during a follow-up period exceeding 21 months. No effect of immunization was noted on lymphocyte counts, mitogenic responses, or delayed-type hypersensitivity. Serum antibody responses to HIV envelope proteins detected by Western blot were seen in 30 of 33 subjects (91%; 95% CI, 71% to 97%) receiving either 40- or 80-micrograms doses of rgp160 and were most commonly of weakly reactive intensity. Responses were first noted by Western blot after the second dose. They markedly increased in frequency after the third dose and declined over the next 12 to 18 months. The administration of a fourth dose resulted in homologous neutralizing activity in sera from 5 to 24 subjects (21%; CI, 7% to 37%) as well as in complement-mediated antibody-dependent enhancement in sera from 6 of 24 subjects (25%; CI, 10% to 42%). Antibody responses were detected by enzyme-linked immunosorbent assay (ELISA) less frequently than by Western blot, and these responses persisted for a shorter time.Conclusions: The administration of rgp160 was well tolerated and safe, resulted in a high rate of antibody response by Western blot after the administration of the third and fourth doses, and generated serum neutralizing activity and complement-mediated antibody-dependent enhancement in some subjects after the fourth dose. [ABSTRACT FROM AUTHOR]

Examines a canarypox vaccine expressing multiple HIV-1 genes. Advantages of canarypox vaccine; Role of T cell in measuring lymphoproliferation; Response of cytotoxic T lymphocytes on the components of the vaccine.