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Background Respiratory syncytial virus (RSV) disease in older adults is undercharacterized. To help inform future immunization policies, this study aimed to describe the disease burden in Canadian adults aged ≥50 years hospitalized with RSV. Methods Using administrative data and nasopharyngeal swabs collected from active surveillance among adults aged ≥50 years hospitalized with an acute respiratory illness (ARI) during the 2012–2013, 2013–2014, and 2014–2015 influenza seasons, RSV was identified using a respiratory virus multiplex polymerase chain reaction test to describe the associated disease burden, incidence, and healthcare costs. Results Of 7797 patients tested, 371 (4.8%) were RSV positive (2.2% RSV-A and 2.6% RSV-B). RSV prevalence varied by season from 4.2% to 6.2%. Respiratory virus coinfection was observed in 11.6% (43/371) of RSV cases, with influenza A being the most common. RSV hospitalization rates varied between seasons and increased with age, from 8–12 per 100 000 population in adults aged 50–59 years to 174–487 per 100 000 in adults aged ≥80 years. The median age of RSV cases was 74.9 years, 63.7% were female, and 98.1% of cases had ≥1 comorbidity. Among RSV cases, the mean length of hospital stay was 10.6 days, 13.7% were admitted to the intensive care unit, 6.4% required mechanical ventilation, and 6.1% died. The mean cost per RSV case was $13 602 (Canadian dollars) but varied by age and Canadian province. Conclusions This study adds to the growing literature on adult RSV burden by showing considerable morbidity, mortality, and healthcare costs in hospitalized adults aged ≥50 years with ARIs such as influenza. [ABSTRACT FROM AUTHOR]

Background There is no uniform guideline for postchemotherapy vaccination of children with acute lymphoblastic leukemia (ALL). We evaluated waning immunity to 14 pneumococcal serotypes, pertussis toxin (PT), tetanus toxoid (TT) and varicella, and immunogenicity of postchemotherapy diphtheria, tetanus, pertussis, hepatitis B, polio, and Haemophilus influenzae type b (DTaP-IPV-Hib) and pneumococcal vaccination among previously vaccinated children treated for ALL. Methods This was a multicenter trial of children with ALL enrolled 4–12 months postchemotherapy completion. Exclusion criteria included: infant ALL, relapsed ALL, and stem cell transplant recipients. Immunocompetent children were recruited as controls. Postchemotherapy participants received DTaP-IPV-Hib and 13-valent pneumococcal conjugate vaccine (PCV13) concurrently, followed by 23-valent pneumococcal polysaccharide vaccine (PPV23) 2 months later. Serology was measured at baseline, 2 and 12 months postvaccination. Adverse events were captured via surveys. Results At enrollment, postchemotherapy participants (n = 74) were less likely than controls (n = 78) to be age-appropriately immunized with DTaP (41% vs 89%, P  < .001) and PCV (59% vs 79%, P  = .008). Geometric mean concentrations (GMCs) to TT, PT, PCV serotypes, and varicella were lower in postchemotherapy participants than controls after adjusting for previous vaccine doses (P  < .001). Two months postvaccination, GMCs to TT, PT, and PCV serotypes increased from baseline (P  < .001 for all antigens) and remained elevated at 12 months postvaccination. Antibody levels to PPV23 serotypes also increased postvaccination (P  < .001). No serious adverse events were reported. Conclusions Children treated for ALL had lower antibody levels than controls against pneumococcal serotypes, tetanus, pertussis, and varicella despite previous vaccination. Postchemotherapy vaccination with DTaP-IPV-Hib, PCV13, and PPV23 was immunogenic and well tolerated. Children with ALL would benefit from systematic revaccination postchemotherapy. Clinical Trials Registration NCT02447718. [ABSTRACT FROM AUTHOR]

Background Recent increases in pertussis morbidity and mortality rates among young infants have led to a recommendation in some countries for vaccination against pertussis during pregnancy. Having data on the burden of pediatric pertussis in a large population over time is important for establishing the true burden of disease in the acellular pertussis (aP) vaccine era. Here, we describe age-specific epidemiology and morbidity and mortality rates in children hospitalized with pertussis over 17 years across Canada in the aP vaccine era. Methods Patients aged ≤16 years who were admitted to 1 of 12 pediatric tertiary-care hospitals across Canada between 1999 and 2015 with confirmed (laboratory-confirmed or epidemiologically linked) or probable (clinically diagnosed) pertussis were included. Results Overall, 1402 patients with pertussis were included. Infants aged <2 months had the highest mean annual incidences of pertussis hospitalization and intensive care unit (ICU) admission (116.40 [95% confidence interval (CI), 85.32–147.49] and 33.48 [95% CI, 26.35–40.62] per 100 000 population, respectively). The overall proportion of children who required ICU admission was 25.46%, and the proportion was highest in infants aged <2 months (37.90%). Over the span of this study, 21 deaths occurred. Age of <16 weeks, prematurity, encephalopathy, and a confirmed pertussis diagnosis were independent risk factors for ICU admission. Age of <4 weeks, prematurity, and female sex were independent risk factors for death. Conclusions In the aP vaccine era, endemic pertussis still contributes considerably to childhood morbidity and death, particularly in infants aged <2 months. Vaccination against pertussis during pregnancy has the potential to reduce this disease burden. [ABSTRACT FROM AUTHOR]

Background: This double-blind study assessed immunogenicity, lot consistency, and safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).Methods: Healthy adults (N = 1197) were randomized 2:2:2:2:1 to receive 1 of 3 consistency lots of rVSVΔG-ZEBOV-GP (2 × 107 plaque-forming units [pfu]), high-dose 1 × 108 pfu, or placebo. Antibody responses pre-/postvaccination (28 days, 6 months; in a subset [n = 566], months 12, 18, and 24) were measured. post hoc analysis of risk factors associated with arthritis following vaccination was performed.Results: ZEBOV-GP enzyme-linked immunosorbent assay (ELISA) geometric mean titers (GMTs) increased postvaccination in all rVSVΔG-ZEBOV-GP groups by 28 days (>58-fold) and persisted through 24 months. The 3 manufacturing lots demonstrated equivalent immunogenicity at 28 days. Neutralizing antibody GMTs increased by 28 days in all rVSVΔG-ZEBOV-GP groups, peaking at 18 months with no decrease through 24 months. At 28 days, ≥94% of vaccine recipients seroresponded (ZEBOV-GP ELISA, ≥2-fold increase, titer ≥200 EU/mL), with responses persisting at 24 months in ≥91%. Female sex and a history of arthritis were identified as potential risk factors for the development of arthritis postvaccination.Conclusions: Immune responses to rVSVΔG-ZEBOV-GP persisted to 24 months. Immunogenicity and safety results support continued rVSVΔG-ZEBOV-GP development.Clinical Trials Registration: NCT02503202. [ABSTRACT FROM AUTHOR]

Background Reduced-antigen-content tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended in many countries for boosting immunity in adolescents and adults. Although immunity to these antigens wanes with time, currently available Tdap products are not labeled for repeat administration in the United States. Methods We performed an observer-blinded, randomized controlled trial in 1330 adults aged 18 to <65 years who received either the Tdap (n = 1002) or tetanus-diphtheria (Td) (n = 328) vaccine 8 to 12 years after a dose of Tdap vaccine administered previously. Solicited adverse events following immunization were documented for 7 days after vaccination, and serious adverse events and adverse events of medical significance were documented for 6 months after vaccination. Levels of antibodies against component vaccine antigens were measured before and 1 month after vaccination. Results A solicited adverse event was reported by 87.7% of Tdap and 88.0% of Td vaccine recipients. We found no significant differences in the rates of injection-site reactions, systemic reactions, or serious adverse events between the vaccine groups. A robust antibody response to each pertussis antigen in the Tdap-vaccinated group was found; postvaccination-to-prevaccination geometric mean antibody concentration ratios were 8:1 (pertussis toxoid), 5.9 (filamentous hemagglutinin), 6.4 (pertactin), and 5.2 (fimbriae 2 and 3). Postvaccination geometric mean concentrations of tetanus antibody (4.20 and 4.74 IU/mL, respectively) and diphtheria antibody (10.1 and 12.6 IU/mL, respectively) were similar in the Tdap and Td groups, and the rates of seroprotection against tetanus and diphtheria were >99% in both groups. Conclusions A second dose of Tdap vaccine in adults approximately 10 years after a previous dose was well tolerated and immunogenic. These data might facilitate consideration of providing Tdap booster doses to adults. [ABSTRACT FROM AUTHOR]

Background Immunization of pregnant women with tetanus-diphtheria-acellular pertussis vaccine (Tdap) provides protection against pertussis to the newborn infant. Methods In a randomized, controlled, observer-blind, multicenter clinical trial, we measured the safety and immunogenicity of Tdap during pregnancy and the effect on the infant’s immune response to primary vaccination at 2, 4, and 6 months and booster vaccination at 12 months of age. A total of 273 women received either Tdap or tetanus-diphtheria (Td) vaccine in the third trimester and provided information for the safety analysis and samples for the immunogenicity analyses; 261 infants provided serum for the immunogenicity analyses. Results Rates of adverse events were similar in both groups. Infants of Tdap recipients had cord blood levels that were 21% higher than maternal levels for pertussis toxoid (PT), 13% higher for filamentous hemagglutinin (FHA), 4% higher for pertactin (PRN), and 7% higher for fimbriae (FIM). These infants had significantly higher PT antibody levels at birth and at 2 months and significantly higher FHA, PRN, and FIM antibodies at birth and 2 and 4 months, but significantly lower PT and FHA antibody levels at 6 and 7 months and significantly lower PRN and FIM antibody levels at 7 months than infants whose mothers received Td. Differences persisted prebooster at 12 months for all antigens and postbooster 1 month later for PT, FHA, and FIM. Conclusions This study demonstrated that Tdap during pregnancy results in higher levels of antibodies early in infancy but lower levels after the primary vaccine series. Clinical Trials Registration NCT00553228. [ABSTRACT FROM AUTHOR]

Background: Respiratory syncytial virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available.Methods: This was a randomized, observer-blinded, first-in-humans study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A, formulated with either the lipid and oil-based vaccine platform DepoVax (DPX-RSV[A]) or alum (RSV[A]-Alum), in healthy, 50-64-year-old individuals. Two dose levels (10 or 25 µg) of SHe with each formulation were compared to placebo. A booster dose was administered on day 56.Results: There was no indication that the vaccine was unsafe. Mild pain, drowsiness, and muscles aches were the most common solicited adverse events (AEs), and the frequencies of the AEs did not increase after dose 2. Robust anti-SHe-specific immune responses were demonstrated in the DPX-RSV(A) 10-μg and 25-μg groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-μg group at day 421. Responses to the RSV(A)-Alum vaccines were very low.Conclusions: A novel antigen from the SH protein of RSV, formulated in a lipid and oil-based vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile. [ABSTRACT FROM AUTHOR]

Background: Influenza is an important cause of morbidity and mortality among older adults. Even so, effectiveness of influenza vaccine for older adults has been reported to be lower than for younger adults, and the impact of frailty on vaccine effectiveness (VE) and outcomes is uncertain. We aimed to study VE against influenza hospitalization in older adults, focusing on the impact of frailty.Methods: We report VE of trivalent influenza vaccine (TIV) in people ≥65 years of age hospitalized during the 2011-2012 influenza season using a multicenter, prospective, test-negative case-control design. A validated frailty index (FI) was used to measure frailty.Results: Three hundred twenty cases and 564 controls (mean age, 80.6 and 78.7 years, respectively) were enrolled. Cases had higher baseline frailty than controls (P = .006). In the fully adjusted model, VE against influenza hospitalization was 58.0% (95% confidence interval [CI], 34.2%-73.2%). The contribution of frailty was important; adjusting for frailty alone yielded a VE estimate of 58.7% (95% CI, 36.2%-73.2%). VE was 77.6% among nonfrail older adults and declined as frailty increased.Conclusions: Despite commonly held views that VE is poor in older adults, we found that TIV provided good protection against influenza hospitalization in older adults who were not frail, though VE diminished as frailty increased.Clinical Trials Registration: NCT01517191. [ABSTRACT FROM AUTHOR]

Background: This study (NCT02503202) evaluated the safety of recombinant vesicular stomatitis virus-Zaire Ebola virus envelope glycoprotein vaccine (rVSVΔG-ZEBOV-GP).Methods: Overall, 1197 subjects were randomized 2:2:2:2:1; 1194 were vaccinated with 1 dose of 1 of 3 lots of rVSVΔG- ZEBOV-GP (2 × 107 plaque-forming units [pfu], n = 797; combined-lots group), a single high-dose lot of rVSVΔG-ZEBOV-GP (1 × 108 pfu, n = 264; high-dose group), or placebo (n = 133). Daily temperatures and adverse events (AEs) were recorded days 1 to 42 postvaccination. Solicited AEs included injection-site AEs from days 1 to 5, and joint pain, joint swelling, vesicular lesions (blisters), and rashes from days 1 to 42. Serious AEs (SAEs) were recorded through 6 months postvaccination.Results: Fever (≥38.0°C) was observed in 20.2% of combined lots (3.2% with ≥39.0°C), 32.2% of high-dose (4.3% with ≥39.0°C), and 0.8% of placebo (0.8% with ≥39.0°C). Incidences of AEs of interest (days 1-42) were arthralgia (17.1% combined lots, 20.4% high-dose, 3.0% placebo), arthritis (5.1% combined lots, 4.2% high-dose, 0.0% placebo), and rash (3.8% combined lots, 3.8% high-dose, 1.5% placebo). Twenty-one SAEs and 2 deaths were reported, all assessed by investigators as unrelated to vaccine.Conclusions: rVSVΔG-ZEBOV-GP was generally well-tolerated, with increased rates of injection-site and systemic AEs compared to placebo, and no vaccine-related SAEs or deaths. These findings support the use of rVSVΔG-ZEBOV-GP vaccine in persons at risk for Ebola virus disease.Clinical Trials Registration: NCT02503202. [ABSTRACT FROM AUTHOR]

Background:  Respiratory syncytial virus (RSV) is a leading cause of childhood bronchiolitis and pneumonia, particularly in early infancy. Immunization of pregnant women could boost preexisting immune responses, providing passive protection to newborns through placental transfer of anti-RSV antibody.Methods:  In this first-in-humans clinical trial of a purified recombinant RSV protein F vaccine engineered to preferentially maintain prefusion conformation (RSV-PreF), 128 healthy men 18-44 years old were randomized to one dose of a RSV-PreF vaccine containing 10, 30, or 60 µg of RSV-PreF antigen, with or without alum adjuvant, or control, and followed for one year for safety and immunogenicity outcomes.Results:  Injection site pain was the most common adverse event, reported by up to 81.3% of participants. The highest RSV neutralizing antibody responses were in the 30 µg RSV-PreF/alum, 60 µg RSV-PreF/alum, and 60 µg RSV-PreF/nonadjuvant groups. Responses were evident on day 7, and 30 days after vaccination these participants had RSV-A neutralizing antibody titers of ≥1:512, and >70% had titers of 1:1024, with titers increasing by 3.2-4.9 fold. Responses remained high on day 60 but waned on days 180 and 360.Conclusions:  The RSV-PreF vaccine elicited rapid RSV neutralizing antibody responses in healthy young men, with an acceptable adverse event profile. [ABSTRACT FROM AUTHOR]

Background. Influenza attack rates are high in 6- to 35-month-old children; vaccines containing both lineages of influenza B (Yamagata and Victoria), in addition to the H3N2 and H1N1 antigens, may improve protection rates. Methods. In a randomized double-blind controlled trial, the immunogenicity and reactogenicity of an inactivated quadrivalent influenza vaccine (QIV) and a trivalent control vaccine (TIV) were assessed. Results. Six hundred one children (QIV, n = 299; TIV, n = 302) were enrolled at 8 sites in 3 countries. The primary immunogenicity objective was met: the lower limit (LL) of the 2-sided 95% confidence interval (CI) for the seroconversion rate in QIV recipients ranged from 66.6% to 81.3%, which was ≥40% against all 4 strains. The immunogenic superiority of the additional B/Victoria strain in the QIV compared to that in the TIV was confirmed: the LL of the 2-sided 95%CI of the geometric mean titer ratio (QIV/TIV) (6.28 [95%CI, 5.32-7.41]) was greater than 1.5, and the LL of the 2-sided 95% CI for the difference in the seroconversion rate (QIV - TIV) (64.19%[95%CI, 57.65%-69.95%]) was greater than 10%. Injection-site pain and irritability/fussinesswere the most commonly reported solicited injection-site and general adverse events, respectively, from days 0 to 6 and were similar in frequency between the groups. Conclusions. In children aged 6 to 35 months, a QIV has superior immunogenicity for the added B strain and acceptable immunogenicity for shared strains, with no notable difference in reactogenicity and safety when compared to a TIV. [ABSTRACT FROM AUTHOR]

Background. Neisseria meningitidis causes 500 000 cases of septicemia and meningitis worldwide annually, with approximately 200 cases in Canada each year. Previous studies describe a case-fatality rate of 5%-15% and up to 20% of survivors suffering from long-term disability. Methods. This study was performed in Canada between 2002 and 2011; the study area included >50% of the country's population.We identified risk factors associated with death and the development of complications in children and adults admitted to hospital with confirmed invasive meningococcal disease (IMD). Clinical information was obtained from hospital records. Risk factors for death and complications were analyzed by univariate and multivariable analyses. Results. Of 868 individuals hospitalized with IMD, there were 73 deaths (8.4%) and 157 (18%) developed complications. The most common complications were hearing loss (5.4%), skin scarring (5.4%), amputation (3.4%), renal dysfunction (2.6%), and seizures (2.5%). Mortality was independently associated with shock (adjusted odds ratio [aOR], 23.30; P < .0001), age (aOR, 1.02 per 1-year increased age; P < .0001), symptom onset within 24 hours of admission (aOR, 1.80; P = .0471), and admission to the intensive care unit (aOR, 0.41; P = .0196). Development of complications was independently associated with seizures (aOR, 4.55; P < .0001), shock (aOR, 3.10; P < .0001), abnormal platelet count (aOR, 2.14; P = .0002), bruising (aOR, 3.17; P = .0059), abnormal white blood cell count (aOR, 0.52; P = .0100), and prior antibiotic exposure (aOR, 0.27; P = .0273). Conclusions. Outcomes following IMD remain poor in this resource-rich setting in the 21st century. These data identify priorities for clinical management of adults and children with IMD, and provide prognostic information for affected patients and their families and cost-effectiveness analyses for meningococcal vaccine programs. [ABSTRACT FROM AUTHOR]

The meningococcal serogroup C conjugate vaccine has significantly reduced serogroup C meningococcal disease in Canada, despite different immunization schedules used in different provinces. Direct and indirect protection was achieved with the largest reduction in the 15–24 year age group.Background. Before 2001, the incidence of invasive meningococcal disease (IMD) in Canada was 1.0 per 100 000 per year, with 40% of cases caused by serogroup C organisms. During 2001–2005 all provinces introduced the meningococcal serogroup C conjugate vaccine (MCCV) into their routine infant immunization schedule.Methods. Active, prospective, population-based surveillance of IMD in children and adults was conducted by the Canadian Immunization Monitoring Program, ACTive (IMPACT) during 2002–2012. Inclusion criteria were admission to hospital and identification of Neisseria meningitidis from a sterile site. Incidence was estimated using population census data from Statistics Canada.Results. Prior to MCCV introduction, serogroup C disease incidence was 0.07–0.25 per 100 000 per year depending on the province. Following vaccine introduction, serogroup C disease decreased to <0.05 per 100 000 per year, with a reduction of 14% per year (P = .0014). A decrease occurred in all provinces, despite differing schedules being implemented. The largest decrease of 83% (from 0.27 to 0.05 per 100 000 per year) occurred in the 15–24 year age group (P = .0100) who were not vaccinated in all provinces. There was no impact on the incidence of nonserogroup C disease over the same period (P = .9811).Conclusions. MCCV dramatically reduced the incidence of serogroup C IMD in Canada through both direct and indirect effects. The observation that disease incidence decreased with different schedules suggests that the doses at 12 months (common to all provinces) and adolescence (7 of 8 provinces studied) were critical in achieving disease control. [ABSTRACT FROM AUTHOR]

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Background Universal immunization of adolescents against meningococcal disease with a quadrivalent meningococcal ACWY (MenACWY) conjugate vaccine is recommended in a number of countries. Methods In a randomized, controlled, observer-blinded, multicenter trial, 1016 participants, 10–25 years of age, were randomly allocated 1:1:1 to receive a single dose of 1 of 2 lots of an investigational tetanus toxoid‐conjugated MenACWY vaccine (MenACWY‐TT) or a marketed diphtheria toxoid‐conjugated MenACWY vaccine (MenACWY‐DT). The primary outcome was the noninferiority of the vaccine response after MenACWY‐TT (lot A) compared with MenACWY‐DT for all 4 serogroups. Vaccine response was defined as a postvaccination human serum bactericidal antibody (hSBA) titer against each of the serogroups of at least 1:8 in persons initially seronegative (<1:4) or as a 4‐fold increase in titer pre‐ to postvaccination in persons initially seropositive (≥1:4). Adverse events (AEs) after immunization were measured 4 and 31 days postvaccination. Results The mean age of participants was 16.3 years; 977 (96.6%) completed the study. The noninferiority of MenACWY‐TT (lot A) to the control vaccine in terms of the percentage of participants with hSBA vaccine response was demonstrated for each serogroup. Vaccine response rates ranged from 51.0% to 82.5% for the 4 serogroups after MenACWY‐TT (both lots) compared with 39.0%–76.3% for the 4 serogroups after MenACWY‐DT. Pain was the most common injection‐site reaction reported by 50.8%–55.4% across the 3 groups. Fatigue and headache were the most common systemic solicited AEs, reported by 27.3%–29.2% and 25.5%–26.4%, respectively. Conclusions Tetanus toxoid‐conjugated MenACWY vaccine was well tolerated and elicited an immune response that was noninferior to that of a marketed MenACWY‐DT (www.clinicaltrials.gov NCT01165242). [ABSTRACT FROM PUBLISHER]

Background. Mismatch between circulating influenza B viruses (Yamagata and Victoria lineages) and vaccine strains occurs frequently.Methods. In a randomized controlled trial, immunogenicity and safety of an inactivated quadrivalent influenza vaccine candidate (QIV) versus trivalent inactivated influenza vaccine (TIV)-Victoria(Vic) and TIV-Yamagata(Yam) in children 3–17 years of age was evaluated. In an open-label study arm, QIV only was assessed in children 6–35 months of age.Results. A total of 3094 children (932 QIV, 929 TIV-Vic, 932 TIV-Yam, and 301 QIV only) were vaccinated. QIV was noninferior to the TIVs for shared strains (A/H3N2 and A/H1N1) based on hemagglutination-inhibition (HI) antibodies 28 days after last vaccination, and superior for the unique B strains Victoria and Yamagata (geometric mean titer ratios 2.61, 3.78; seroconversion rate differences 33.96%, 44.63%). Among children in the randomized trial, adverse event rates were similar except for injection site pain (dose 1: 65.4% QIV, 54.6% TIV-Vic, 55.7% TIV-Yam).Conclusion. QIV elicited superior HI responses to the added B strains compared to TIV controls, potentially improving its effectiveness against influenza B. HI responses were similar between QIV and TIV controls for the shared strains. QIV had an acceptable safety profile relative to TIVs.Clinical Trials Registration. NCT01198756. [ABSTRACT FROM AUTHOR]

Background. Group A streptococcus (GAS) causes illness ranging from uncomplicated pharyngitis to life-threatening necrotizing fasciitis, toxic shock, and rheumatic fever. Attempts to develop an M protein-based vaccine have been hindered by the fact that some M proteins elicit both protective antibodies and antibodies that cross-react with human tissues. New molecular techniques have allowed the previous obstacles to be largely overcome. Methods. The vaccine is comprised of 4 recombinant proteins adsorbed to aluminum hydroxide that contain N-terminal peptides from streptococcal protective antigen and M proteins of 26 common pharyngitis, invasive, and/or rheumatogenic serotypes. Thirty healthy adult subjects received intramuscular 26-valent GAS vaccine (400 μg) at 0, 1, and 4 months, with clinical and laboratory follow-up for safety and immunogenicity using assays for tissue cross-reactive antibodies, type-specific M antibodies to 27 vaccine antigens, and functional (opsonization) activity of M protein antibodies. Results. The incidence of local reactogenicity was similar to that for other aluminum hydroxide-adsorbed vaccines in adults. No subject developed evidence of rheumatogenicity or nephritogenicity, and no induction of human tissue-reactive antibodies was detected. Overall, 26 of 27 antigenic peptides evoked a >4-fold increase in the geometric mean antibody titer over baseline. The mean log2 fold-increase in serum antibody titer (± standard error of the mean) for all 27 antigens was 3.67 ± 0.21. A significant mean log2 reduction in streptococcal bacterial counts in serum samples obtained after immunization was seen in opsonization assays for all M serotypes. Conclusions. On the basis of epidemiological data demonstrating that the majority of cases of pharyngitis, necrotizing fasciitis, and other invasive streptococcal infections are caused by a limited number of serotypes, this 26-valent vaccine could have significant impact on the overall burden of streptococcal disease. [ABSTRACT FROM AUTHOR]

Reports on carotid artery dissection as a possible severe complication of pertussis in adults. Complications due to paroxysmal coughing; Prevention against the disease by adult booster immunization.

Presents letters to the editor about infectious diseases published in the November 15, 2002 issue of the 'Journal of Infectious Diseases.' Identification of indigeneous hepatitis E virus from a Japanese patient who contracted sporadic acute hepatitis in 1982; Changing age and seasonal profile of pertussis in British Columbia.

Examines the changing age and seasonal profile of pertussis in British Columbia. Decline in the incidence of pertussis; Reduction of susceptibility; Changes in the childhood immunization program.

Presents the results of a nationwide epidemiological study of invasive pneumococcal infections in Canadian children from 1991 to 1998. Effects of vaccination on colonization rates with vaccine serotypes; Age distribution of invasive infections; Factors to consider in establishing vaccination strategies.

Examines the effect of age on the clinical presentation of pertussis in adolescents and adults. Percentage of cases by vaccination status, history of prior pertussis, symptoms, complications and investigations; Clinical presentation by smokers and persons with asthma; Use of prophylaxis.

Assesses the morbidity associated with the continued high levels of pertussis among Canadian children less than two years of age who were admitted to the Immunization Monitoring Program-Active centers. Complications caused by pertussis; Influence of pertussis on morbidity and mortality rates in Canada.

Assesses the safety and antibody response to a three-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids and inactivated poliovirus vaccine given separately or combined as a single injection with a Haemophilus influenzae type b-tetanus toxoid conjugate vaccine to infants receiving their first four doses. Antibody levels of combined vaccine recipients; Immunogenicity of the vaccines.

Describes a study which evaluated the ability of physicians to make a diagnosis of pertussis in children and factors associated with improved diagnosis in Quebec. Methodology; Results; Discussion.

To determine if inactivated poliovirus vaccine combined with diphtheria and tetanus toxoids and whole-cell pertussis vaccine interferes with the immunogenicity of pertussis vaccine, we performed a randomized trial of diphtheria and tetanus toxoids and pertussis vaccine combined with inactivated poliovirus vaccine given as a single injection or as two separate injections at the same visit to infants immunized at 2, 4, and 6 months of age. A total of 84 infants were enrolled in the study; 44 received the single injection, and 40 received separate injections. Before immunization, there were no differences in antibody values between the two groups. After two vaccine doses, infants immunized with the single injection had significantly lower values of antibody to filamentous hemagglutinin (8.3 vs. 23.7 ELISA units; P < .001), fimbriae (266.5 vs. 771.8 ELISA units; P < 0.01), and the 69kD membrane protein (442.2 vs. 1,352ELISA units; P < .001). After the third dose, these differences persisted, and differences were also detected for antibody to pertussis toxin (10.0 vs. 35.5 ELISA units; P < .001) and a whole-bacteria antigen preparation (2,667 vs. 3,829 ELISA units; P < .05). We conclude that there is a diminished antibody response to the pertussis vaccine when inactivated poliovirus vaccine is combined with the diphtheria and tetanus toxoids and pertussis vaccine. [ABSTRACT FROM PUBLISHER]

Three monoclonal antibodies to pertussis toxin were characterized and used to investigate its role in immunity. Antibody affinity correlated with toxin neutralization in in vivo and in vitro assays but was not the only determinant of protection against Bordetella pertussis infection. B9, a high-affinity anti-S3 antibody, was the most effective in neutralizing toxin-induced CHO cell clustering and hemagglutination in vitro and lymphocytosis and histamine sensitization in vivo. A4, a similar-affinity anti-S1 antibody, was less active in the toxin neutralization assays but more protective in the mouse infection model. A12, a low-affinity anti-S1 antibody, was least active in the assays of toxin neutralization but as effective as B9 in the infection model. These data suggest that epitopes on the A protomer and B oligomer may induce protective immunity. Measurement of pertussis toxin neutralization by monoclonal antibodies in in vitro and in vivo assays may not accurately predict protection against infection with B. pertussis. [ABSTRACT FROM PUBLISHER]

In a test of the hypothesis that lysogeny of group A streptococci by a temperate bacteriophage might confer nephritogenicity, 283 sera from 69 patients were examined for IgG and IgM antibodies to M 49 streptococcal bacteriophage hyaluronidase. The IgG and IgM response to bacteriophage hyaluronidase was greatest in M 49 streptococci-infected individuals with nephritis, butM 49 streptococci-infected subjects without nephritis also had a greater immune response than did subjects infected with serotypes other than M 49. Although antibody to bacterial hyaluronidase was detected in all Streptococcus-infected groups, antibody to M 49 streptococcal bacteriophage hyaluronidase usually was found in onlyM 49 streptococci-infected patients. Although the greatest IgG and IgM antibody response to bacteriophage hyaluronidase can be demonstrated in individuals with glomerulonephritis, the antibody response does not indicate a direct relation of lysogeny and nephritis because subjects with and without nephritis after M 49 streptococcal infection all had a significant rise in antibody titer. [ABSTRACT FROM PUBLISHER]

Background Inactivated influenza vaccines (IV) efficacy is variable and sometimes poor. In this phase 1 trial the safety and immunogenicity of a novel nanoparticle adjuvant (Papaya Mosaic Virus (PapMV or PAL) at different dose levels combined with inactivated trivalent IV (TIV; FLUVIRAL® 2013–2014, GSK, Kirkland PQ) was assessed. Nonpathogenic in mammals, PAL is recognized as a pathogen-associated molecular pattern (PAMP) which stimulates innate, cell-mediated immunity (CMI) and adaptive immunity in naïve mice through activation of toll like receptor 7 and 8. Methods Healthy persons 18–50 years of age were randomized to one of 6 study groups: 30 µg, 60 µg, 120 µg or 240 µg of PAL with 0.25 mL TIV, 240 µg of PAL with 0.125 mL TIV, or control (0.5 mL TIV). Solicited local and general adverse events (AE) were collected Day (D)0 to 6, unsolicited AE to D28, and serious AE to D1095. Hemagglutination-inhibition assays (HI), antibody to Influenza A virus nucleoprotein (NP), and peripheral blood mononuclear cells (PBMC) for measurement of interferon-gamma (IFNg) ELISPOT (response to PepMix influenza A H2N2 Ann Arbour NP, MP1, and an influenza peptide pool), granzyme B, and IFNg:IL:10 ratio were collected on D0, 7, 28, 120, and 180. Results The most common solicited AEs were transient mild-to-moderate local pain (62.5%–87.5% of participants/group), drowsiness (≤37.5% of participants/group) and generalized muscle aches (12.5–50% of participants/group). There was one unrelated SAE. All participants had HI and anti-NP titers at baseline. HI GMTs increased at D28 post vaccine in most groups (Figure 1) and waned over time. HI fold Ab (Far) responses to TIV strains were poor in all groups (≤37.5% of participants/group had 4-Far to any strain). CMI results were consistent with humoral responses. Conclusion The PAL adjuvant in doses of 30 to 240µg combined with reduced TIV dosages was safe with no signals up to 3 years after vaccine. Reduced doses of TIV co-presented with 240 µg PAL had similar HI GMTs as TIV. The CMI results suggest that the assessment of PAL efficacy on TIV immunization would have to be conducted in an influenza naïve population. Disclosures Scott Halperin, MD, GlaxoSmithKline: Ad hoc advisory boards, Other Financial or Material Support, Research Grant; Janssen Pharm: Research Grant; sanofi pasteur: Ad hoc advisory boards, Other Financial or Material Support, Research Grant. [ABSTRACT FROM AUTHOR]

The article offers the authors' comments on a recent report from UNICEF which found that immunization rates for children in Canada are too low. According to the authors, availability of electronic immunization registries in more Canadian provinces will help to monitor all children through the recommended immunizations.

Despite pertussis vaccination rates in excess of 95%, pertussis rates in the United States have been rising over the last 30 years, with increasingly larger outbreaks in 2004, 2010, and 2012. The reasons for this resurgence of pertussis are not clearly understood. The recent development of a baboon model of pertussis, along with the future development of a human challenge model of pertussis, has the potential to provide a path forward for answering critical questions about pertussis pathogenesis and host responses and will likely aid in the development of next-generation pertussis vaccines. [ABSTRACT FROM AUTHOR]