Scott A Halperin

Publications (114)491.1 Total impact

• Article: Controlling serogroup B invasive meningococcal disease: the Canadian perspective.

  Julie A Bettinger, Shelley L Deeks, Scott A Halperin, Raymond Tsang, David W Scheifele
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  ABSTRACT: With publically funded meningococcal immunization programs established in infants, children and adolescents, Canada is at the forefront of invasive meningococcal disease prevention. The advent of two new serogroup B vaccines that may protect against multiple disease-causing strains offers the potential to reduce endemic disease to very low levels in Canada. Canada likely will be one of the first countries with approval to use recombinant serogroup B vaccine. However, inclusion of these new vaccines into public immunization programs will be decided at the provincial/territorial level, rather than nationally, and may result initially in different immunization schedules throughout the country as we have seen with conjugate meningococcal vaccines. Such heterogeneous use and adoption of new vaccines complicates disease control, but may assist in evaluation of effectiveness. Minimally, it requires regionally specific information. In this article, the authors provide an overview of the Canadian epidemiology, serogroup B vaccine characteristics, potential strain coverage, immunization strategies and remaining postmarketing research questions.
  Expert Review of Vaccines 05/2013; 12(5):505-17. · 4.25 Impact Factor
• Article: Immunogenicity of 2 doses of HPV vaccine in younger adolescents vs 3 doses in young women: a randomized clinical trial.

  Simon R M Dobson, Shelly McNeil, Marc Dionne, Meena Dawar, Gina Ogilvie, Mel Krajden, Chantal Sauvageau, David W Scheifele, Tobias R Kollmann, Scott A Halperin, Joanne M Langley, Julie A Bettinger, Joel Singer, Deborah Money, Dianne Miller, Monika Naus, Fawziah Marra, Eric Young
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  ABSTRACT: Global use of human papillomavirus (HPV) vaccines to prevent cervical cancer is impeded by cost. A 2-dose schedule for girls may be possible. To determine whether mean antibody levels to HPV-16 and HPV-18 among girls receiving 2 doses was noninferior to women receiving 3 doses. Randomized, phase 3, postlicensure, multicenter, age-stratified, noninferiority immunogenicity study of 830 Canadian females from August 2007 through February 2011. Follow-up blood samples were provided by 675 participants (81%). Girls (9-13 years) were randomized 1:1 to receive 3 doses of quadrivalent HPV vaccine at 0, 2, and 6 months (n = 261) or 2 doses at 0 and 6 months (n = 259). Young women (16-26 years) received 3 doses at 0, 2, and 6 months (n = 310). Antibody levels were measured at 0, 7, 18, 24, and 36 months. MAIN OUTCOMES AND MEASURES: Primary outcome was noninferiority (95% CI, lower bound >0.5) of geometric mean titer (GMT) ratios for HPV-16 and HPV-18 for girls (2 doses) compared with young women (3 doses) 1 month after last dose. Secondary outcomes were noninferiority of GMT ratios of girls receiving 2 vs 3 doses of vaccine; and durability of noninferiority to 36 months. The GMT ratios were noninferior for girls (2 doses) to women (3 doses): 2.07 (95% CI, 1.62-2.65) for HPV-16 and 1.76 (95% CI, 1.41-2.19) for HPV-18. Girls (3 doses) had GMT responses 1 month after last vaccination for HPV-16 of 7736 milli-Merck units per mL (mMU/mL) (95% CI, 6651-8999) and HPV-18 of 1730 mMU/mL (95% CI, 1512-1980). The GMT ratios were noninferior for girls (2 doses) to girls (3 doses): 0.95 (95% CI, 0.73-1.23) for HPV-16 and 0.68 (95% CI, 0.54-0.85) for HPV-18. The GMT ratios for girls (2 doses) to women (3 doses) remained noninferior for all genotypes to 36 months. Antibody responses in girls were noninferior after 2 doses vs 3 doses for all 4 vaccine genotypes at month 7, but not for HPV-18 by month 24 or HPV-6 by month 36. Among girls who received 2 doses of HPV vaccine 6 months apart, responses to HPV-16 and HPV-18 one month after the last dose were noninferior to those among young women who received 3 doses of the vaccine within 6 months. Because of the loss of noninferiority to some genotypes at 24 to 36 months in girls given 2 doses vs 3 doses, more data on the duration of protection are needed before reduced-dose schedules can be recommended. clinicaltrials.gov Identifier: NCT00501137.
  JAMA The Journal of the American Medical Association 05/2013; 309(17):1793-802. · 30.03 Impact Factor
• Article: Functional analysis of paralogous thiol-disulfide oxidoreductases in Streptococcus gordonii.

  Lauren Davey, Crystal K W Ng, Scott A Halperin, Song F Lee
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  ABSTRACT: Disulfide bonds are important for the stability of many extracellular proteins, including bacterial virulence factors. Formation of these bonds is catalyzed by thiol-disulfide oxidoreductases (TDORs). Little is known about their formation in Gram-positive bacteria, particularly among facultative anaerobic Firmicutes such as streptococci. To investigate disulfide bond formation in Streptococcus gordonii, we identified five putative TDORs from the sequenced genome. Each of the putative TDOR genes was insertionally inactivated with an erythromycin resistance cassette and the mutants were analyzed for autolysis, extracellular DNA release, biofilm formation, bacteriocin production, and genetic competence. This analysis revealed a single TDOR, SdbA, which exhibited a pleiotropic mutant phenotype. Using an in silico analysis approach, we identified the major autolysin AtlS as a natural substrate of SdbA, and showed that SdbA is critical to the formation of a disulfide bond that is required for autolytic activity. Analysis by BLAST search revealed homologs to SdbA in other Gram-positive species. This study provides the first in vivo evidence of an oxidoreductase, SdbA, that affects multiple phenotypes in a Gram-positive bacterium. SdbA shows low sequence homology to previously identified oxidoreductases, suggesting that it may belong to a different class of enzymes. Our results demonstrate that SdbA is required for disulfide bond formation in S. gordonii, and indicate that this enzyme may represent a novel type of oxidoreductase in Gram-positive bacteria.
  Journal of Biological Chemistry 04/2013; · 4.77 Impact Factor
• Article: Diversity of Canadian meningococcal serogroup B isolates and estimated coverage by an investigational meningococcal serogroup B vaccine (4CMenB).

  Julie A Bettinger, David W Scheifele, Scott A Halperin, Wendy Vaudry, Jamie Findlow, Ray Borrow, Duccio Medini, Raymond Tsang
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  ABSTRACT: BACKGROUND: In collaboration with the Canadian Immunization Monitoring Program Active (IMPACT), the National Microbiology Laboratory, the UK Health Protection Agency and Novartis Vaccines, we tested the potential of an investigational 4-component meningococcal B vaccine (4CMenB) to cover Canadian strains circulating from 2006 to 2009. METHODS: IMPACT meningococcal surveillance is population based and includes over 50% of Canadian adults and children. All isolates were characterized by Meningococcal Antigen Typing System (MATS) and sequencing for factor H-binding protein (fHbp), Neisseria Heparin Binding Antigen (NHBA) and Neisserial adhesin A (NadA). RESULTS: In total, 157 isolates were tested. Overall, 4CMenB MATS predicted strain coverage was 66% (95% CI: 46-78%), with 26%, 29% and 11% of strains covered by one, two and three vaccine antigens, respectively. The coverage of each antigen was as follows: 13% PorA, 1% NadA, 52% fHbp and 51% NHBA. The majority of strains for clonal complex (cc) 41/44 and cc60 were covered by NHBA; the majority of strains for cc269 and cc32 were covered by fHbp and NHBA. Coverage for two prevalent strains (sequence type (ST)-269 and ST-154) was 95% and 100%, respectively. CONCLUSIONS: 4CMenB has the potential to protect against a significant proportion of Canadian invasive MenB strains.
  Vaccine 04/2013; · 3.77 Impact Factor
• Article: Immunogenicity of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in nonresponders to licensed hepatitis B vaccine.

  Scott A Halperin, Brian J Ward, Marc Dionne, Joanne M Langley, Shelly A McNeil, Bruce Smith, Donna Mackinnon-Cameron, William L Heyward, J Tyler Martin
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  ABSTRACT: An additional one to three doses of hepatitis B vaccine are recommended for nonresponders to an initial standard three-dose series. We compared the safety and immunogenicity of an investigational hepatitis B surface antigen vaccine (HBsAg-1018) with a phosphorothioate oligodeoxyribonucleotide adjuvant that targets toll-like receptor-9 to a commercially available, alum-adjuvanted hepatitis B vaccine (HBsAg-Eng) in nonresponders to three previous doses (primary study) or to four to six previous doses (substudy) of HBsAg-Eng. Both vaccines were well tolerated, although HBsAg-1018 was associated with more injection-site tenderness (63.2% vs. 18.8%, p = 0.016 in the primary study and 81.8% vs. 15.4%, p = 0.003 in the substudy). No statistically significant differences in rates of seroprotection (anti-HBs concentration ≥ 10 mIU/mL) or geometric mean antibody concentrations were found in the primary study. In the substudy, a greater proportion of HBsAg-1018 recipients achieved an anti-HBs concentration ≥ 100 mIU/mL (54.5% vs. 8.3%, p = 0.027), and those responders had higher geometric mean antibody concentrations at 4 weeks (264 vs. 46.5 mIU/mL, p = 0.021) and 52 weeks (7.0 vs. 1.2 mIU/mL, p = 0.030) than HBsAg-Eng recipients. Although this study suggests that HBsAg-1018 may have improved immunogenicity in nonresponders to hepatitis B vaccine vaccination when compared with HBsAg-Eng, larger studies are required.
  Human vaccines & immunotherapeutics. 04/2013; 9(7).
• Article: Response to the changing epidemiology of meningococcal disease in North America 1945-2010.

  Julie A Bettinger, David W Scheifele, Scott A Halperin, Wendy Vaudry, Nicole Le Saux
  Human vaccines & immunotherapeutics. 03/2013; 9(6).
• Article: Safety and immunogenicity of 2010–2011 A/H1N1pdm09-containing trivalent inactivated influenza vaccine in adults previously given AS03-adjuvanted H1N1 2009 pandemic vaccine: results of a randomized trial.

  David W Scheifele, Marc Dionne, Brian J Ward, Curtis Cooper, Otto G Vanderkooi, Yan Li, Scott A Halperin
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  ABSTRACT: Many Canadians received a novel AS03-adjuvanted vaccine during the 2009 influenza A/H1N1 pandemic. Longer term implications of adjuvant use were unclear: would anti-H1N1 immune responses persist at high levels and, if so, could that result in increased or unusual adverse effects upon re-exposure to H1N1pdm09 antigen in the trivalent influenza vaccine (TIV) for 2010-11? To answer these questions, adults given AS03-adjuvanted H1N1pdm09 vaccine (Arepanrix®, GSK Canada) 9-10 mo earlier were enrolled in an evaluator-blinded, crossover trial to receive 2010-2011 non-adjuvanted TIV (Fluviral®, GSK Canada) and placebo 10 d apart, in random order. Adverse effects were monitored for 7 d after each injection. Vaccine-attributable adverse event (VAAE) rates were calculated by subtracting rates after placebo from those after vaccine. Blood was obtained pre-vaccination and 21-30 d afterward to measure hemagglutination inhibiting antibody titers. In total, 326 participants were enrolled and 321 completed the study. VAAE rates were low except for myalgia (18.6%) and injection site pain (63.2%). At baseline, H1N1pdm09 titers ≥ 40 were present in 176/325 subjects (54.2%, 95% confidence interval 48.6, 59.7), with a geometric mean titer (GMT) of 37.4 (95% CI 32.8, 42.6). Post-immunization, 96.0% (95% CI 92.3, 97.8) had H1N1pdm09 titers ≥ 40, with GMT of 167.4 (95% CI 148.7, 188.5). Responses to both influenza A strains in TIV were similar, implying no lasting effect of adjuvant exposure. In summary, titers ≥ 40 persisted in only half the participants 9-10 mo after adjuvanted pandemic vaccine but were restored in nearly all after TIV vaccination, with minimal increase in adverse effects.
  Human vaccines & immunotherapeutics. 01/2013; 9(1):136-43.
• Article: Safety and Immunogenicity of a Hexavalent Vaccine Administered at 2, 4 and 6 Months of Age With or Without a Heptavalent Pneumococcal Conjugate Vaccine: A Randomized, Open-label Study.

  Bruce Tapiéro, Scott A Halperin, Mark Dionne, William Meekison, Francisco Diaz-Mitoma, Paul Zickler, Earl Rubin, Joanne Embree, Prakash Bhuyan, Andrew W Lee, Minran Li, Antigona Tomovici
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  ABSTRACT: BACKGROUND:: DTaP5-IPV-Hib-HepB, an investigational hexavalent combination vaccine, was evaluated for safety and immunogenicity, when administered to infants with heptavalent pneumococcal conjugate vaccine (PCV7). METHODS:: Infants were randomized to receive DTaP5-IPV-Hib-HepB plus PCV7, DTaP5-IPV-Hib-HepB with PCV7 administered 1 month later or DTaP5-IPV/Hib plus HepB plus PCV7 at 2, 4 and 6 months of age in an open-label, phase IIb trial. Vaccine responses were assessed by pertussis toxoid, filamentous hemagglutinin, pertactin and fimbriae types 2/3 seroconversion rates, Haemophilus influenzae type b polyribosylribitol phosphate capsular polysaccharide, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus types 1, 2 and 3 seroprotection rates and geometric mean titers. Solicited injection site and systemic reactions, serious adverse events, and other safety outcomes were reported. RESULTS:: Seroprotection rates to polyribosylribitol phosphate, hepatitis B surface antigen, diphtheria toxoid, tetanus toxoid and poliovirus antigens across all groups met or exceeded predetermined acceptability criteria. Seroconversion rates to pertussis toxoid, pertactin and fimbriae types 2/3, but not filamentous hemagglutinin, met such criteria. Antidiphtheria antibodies were significantly lower when PCV7 was coadministered. Geometric mean titers to the other antigens of the hexavalent and PCV7 vaccines were all high and similar in the 2 groups. No safety signals were noted. CONCLUSIONS:: DTaP5-IPV-Hib-HepB administered at 2, 4 and 6 months of age concomitantly with PCV7 was well tolerated and elicited robust antibody responses to all but the antidiphtheria antigens for which there may be evidence of immune interference. Only filamentous hemagglutinin did not meet seroconversion rate acceptability criteria.
  The Pediatric Infectious Disease Journal 01/2013; 32(1):54-61. · 3.58 Impact Factor
• Article: Molecular characterization of rotavirus isolates from select Canadian pediatric hospitals.

  Andrew McDermid, Nicole Le Saux, Elsie Grudeski, Julie A Bettinger, Kathy Manguiat, Scott A Halperin, Lily Macdonald, Pierre Déry, Joanne Embree, Wendy Vaudry, Timothy F Booth
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  ABSTRACT: BACKGROUND: We report the first multi-site rotavirus genotype analysis in Canada. Prior to this study, there was a dearth of rotavirus G and P genotyping data in Canada. Publically funded universal rotavirus vaccination in Canada started in 2011 and has been introduced by four provinces to date. Uptake of rotavirus vaccines in Canada prior to 2012 has been very limited. The aim of this study was to describe the genotypes of rotavirus strains circulating in Canada prior to widespread implementation of rotavirus vaccine by genotyping samples collected from selected paediatric hospitals. Secondly we identified rotavirus strains that differed genetically from those included in the vaccines and which could affect vaccine effectiveness. METHODS: Stool specimens were collected by opportunity sampling of children with gastroenteritis who presented to emergency departments. Samples were genotyped for G (VP7) genotypes and P (VP4) genotypes by hemi-nested multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9 strains to investigate their relationship to G9 strains that have circulated in other regions of the world. RESULTS: 348 samples were collected, of which 259 samples were rotavirus positive and genotyped. There were 34 rotavirus antigen immunoassay negative samples genotyped using PCR-based methods. Over the four rotavirus seasons, 174 samples were G1P[8], 45 were G3P[8], 22 were G2P[4], 13 were G9P[8], 3 were G4P[8] and 2 were G9P[4]. Sequence analysis showed that all Canadian G9 isolates are within lineage III. CONCLUSIONS: Although a limited number of samples were obtained from a median of 4 centres during the 4 years of the study, it appears that currently approved rotavirus vaccines are well matched to the rotavirus genotypes identified at these hospitals. Further surveillance to monitor the emergence of rotavirus genotypes in Canada is warranted.
  BMC Infectious Diseases 11/2012; 12(1):306. · 3.12 Impact Factor
• Article: Comparison of children hospitalized with seasonal versus pandemic influenza A, 2004-2009.

  Dat Tran, Wendy Vaudry, Dorothy L Moore, Julie A Bettinger, Scott A Halperin, David W Scheifele, Samina Aziz
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  ABSTRACT: The extent to which pandemic H1N1 influenza (pH1N1) differed from seasonal influenza remains uncertain. By using active surveillance data collected by the Immunization Monitoring Program, Active at 12 Canadian pediatric hospitals, we compared characteristics of hospitalized children with pH1N1 with those with seasonal influenza A. We compared demographics, underlying health status, ICU admission, and mortality during both pandemic waves versus the 2004/2005 through the 2008/2009 seasons; influenza-related complications and hospitalization duration during pH1N1 wave 1 versus the 2004/2005 through the 2008/2009 seasons; and presenting signs and symptoms during both pH1N1 waves versus the 2006/2007 through the 2008/2009 seasons. We identified 1265 pH1N1 cases (351 in wave 1, 914 in wave 2) and 1319 seasonal influenza A cases (816 from 2006/2007 through 2008/2009). Median ages were 4.8 (pH1N1) and 1.7 years (seasonal influenza A); P < .0001. Preexisting asthma was overrepresented in pH1N1 relative to seasonal influenza A (13.8% vs 5.5%; adjusted P < .0001). Symptoms more often associated with pH1N1 wave 1 versus seasonal influenza A were cough, headache, and gastrointestinal symptoms (adjusted P < .01 for each symptom). pH1N1 wave 1 cases were more likely to have radiologically confirmed pneumonia (adjusted odds ratio = 2.1; 95% confidence interval = 1.1-3.8) and longer median length of hospital stay (4 vs 3 days; adjusted P = .003) than seasonal influenza A. Proportions of children requiring intensive care and deaths in both pH1N1 waves (14.6% and 0.6%, respectively) were not significantly different from the seasonal influenza A group (12.7% and 0.5%, respectively). pH1N1 in children differed from seasonal influenza A in risk factors, clinical presentation, and length of hospital stay, but not ICU admission or mortality.
  PEDIATRICS 08/2012; 130(3):397-406. · 4.47 Impact Factor
• Article: The Disease Burden of Invasive Meningococcal Serogroup B Disease in Canada.

  Julie A Bettinger, David W Scheifele, Nicole Le Saux, Scott A Halperin, Wendy Vaudry, Raymond Tsang
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  ABSTRACT: INTRODUCTION: Invasive meningococcal disease remains a rare but deadly infection in Canada. New serogroup B vaccines may offer the potential for prevention and control. This report examines the disease burden caused by serogroup B invasive meningococcal infections. METHODS: From 2002 - 2011, active, population-based metropolitan area surveillance for adult and pediatric hospital admissions for laboratory confirmed infection with Neisseria meningitidis was conducted by the 12 centers of the Canadian Immunization Monitoring Program, Active. RESULTS: A total of 769 invasive meningococcal cases occurred from 2002-2011; 54% (n=413) in children with a peak incidence of 6.16 (95% CI 3.18 - 10.76) per 100,000 in children < 1 year of age in 2009. Serogroup B accounted for the largest proportion of cases and had the highest incidence of all serogroups across all ages, with a peak incidence of 0.31 (0.23 - 0.40) per 100,000 in 2007. Serogroup B case fatality rate was 4.3% in children and 21% of pediatric survivors had sequelae. B:17:P1.19 ST-269 was the most frequently detected antigenic type. CONCLUSIONS: Serogroup B invasive meningococcal infections caused substantial morbidity and mortality and are the leading cause of invasive meningococcal disease in Canada. The proportion of cases potentially preventable with the new serogroup B vaccines should be evaluated to determine whether universal immunization programs are warranted.
  The Pediatric Infectious Disease Journal 08/2012; · 3.58 Impact Factor
• Article: A randomized control trial comparing immunogenicity, safety, and preference for self- versus nurse-administered intradermal influenza vaccine.

  Brenda L Coleman, Allison J McGeer, Scott A Halperin, Joanne M Langley, Yassein Shamout, Anna Taddio, Vibhuti Shah, Shelly A McNeil
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  ABSTRACT: Intradermally administered influenza vaccine is as immunogenic as intramuscular vaccine at a lower unit dose. New microinjection systems could allow self-administration of vaccine, potentially reducing the cost and inconvenience. To compare the immunogenicity, reactogenicity, success rate, and acceptability of self- versus nurse-administered intradermal trivalent seasonal influenza vaccine. Adults (18-59years old) were randomized to either self- or nurse-administered intradermal vaccine. Prior to vaccination, participants completed a questionnaire and had blood drawn for hemagglutination inhibition titres. Participants in the nurse-administered group were vaccinated by study personnel. The self-administered group were given an instruction sheet and administered their own vaccine. All participants completed a questionnaire and adverse event diaries for 21days post vaccination, at which time blood was again collected. Of the 228 participants, 115 were randomized to self-administration and 113 to nurse administration. Groups did not differ by sex, age, or levels of seroprotection at baseline. Of the 114 who completed self-administration, 106 (93%) were successful on the first attempt. There were no group differences in measures of immunogenicity for any of the strains. Self-administering participants reported a lower mean pain rating at vaccination but had larger areas of redness post-vaccination. Seventy percent of all participants said they would prefer intradermal over intramuscular vaccinations in the future, if given the choice. Compared to nurse-administered intradermal influenza vaccine, self-administered vaccine was immunologically non-inferior and reached all EMA immunogenicity criteria for the A strains, was highly successful and well-accepted by study participants. Together, these data provide preliminary evidence of feasibility for this method of influenza vaccine administration, which may improve vaccine uptake in adults and increase efficiency of vaccine delivery during outbreaks.
  Vaccine 08/2012; 30(44):6287-93. · 3.77 Impact Factor
• Article: Safety and immunogenicity of different two-dose regimens of an investigational hepatitis B vaccine (hepatitis B surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide) in healthy young adults.

  Scott A Halperin, Shelly McNeil, Joanne M Langley, Bruce Smith, Donna MacKinnon-Cameron, Robyn McCall-Sani, William L Heyward, J Tyler Martin
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  ABSTRACT: Previous studies have shown that two doses of an investigational hepatitis B vaccine consisting of hepatitis B surface antigen combined with an immunostimulatory phosphorothioate oligodeoxyribonucleotide adjuvant (HBV-ISS) given 8 weeks apart provides seroprotection sooner than 3 doses of a licensed hepatitis B vaccine over 24 weeks. A more rapid schedule with a 4-week interval could provide earlier protection and potentially greater compliance. In this randomized, double-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 or 0 and 8 weeks; saline placebo was given at week 8 for the 0-4 schedule and at week 4 for the 0-8 schedule). Adverse events were collected after each dose. Antibodies were measured at 0, 4, 8, 12, and 32 weeks. Participants were randomized to the 0-4 (n=18) or 0-8 (n=23) weeks schedule. Rates of adverse events were similar in the two groups after the HBV-ISS injections regardless of the schedule, but more frequent than after the placebo injections. By 4 weeks post-dose-2, 94.1% of 0-4 and 100% of 0-8 recipients had protective antibody levels; geometric mean concentrations were 244 mIU/mL and 3217 mIU/mL respectively. By 32 weeks, the difference in antibody concentration had decreased (GMC 439 mIU/mL vs. 863 mIU/mL, respectively; p=0.04). A 0-4 weeks, two-dose regimen of HBV-ISS was well-tolerated and induced an antibody response that was similar to a 0-8 weeks schedule.
  Vaccine 06/2012; 30(36):5445-8. · 3.77 Impact Factor
• Source

  Available from: Janice E Graham

  Article: Challenges to immunization: the experiences of homeless youth.

  Alexander Doroshenko, Jill Hatchette, Scott A Halperin, Noni E MacDonald, Janice E Graham
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  ABSTRACT: Homelessness is a critical social issue, both a product of, and contributing to, poor mental and physical health. Over 150,000 young Canadians live on the streets. Homeless youth experience a high incidence of infectious diseases, many of which are vaccine preventable. Early departure from school and limited access to public health services makes them a particularly vulnerable high-risk group. This study explores challenges to obtaining essential vaccines experienced by homeless youth. A qualitative research study to explore knowledge, attitudes, beliefs, and experiences surrounding immunization of hard-to-reach homeless youth was designed. Participants were recruited for focus groups from Phoenix House and Shelter, a non-profit, community-based organization assisting homeless youth in Halifax, Nova Scotia, Canada. An experienced facilitator guided the recorded discussions. Transcripts of audiotapes were analyzed using a constant comparative method until data revealed a set of exemplars and themes that best captured participants' knowledge, attitudes, beliefs and experiences surrounding immunization and infectious diseases. Important themes emerged from our analysis. Considerable variability in knowledge about immunization and vaccine preventable diseases was found. The homeless youth in the study had limited awareness of meningitis in contrast to a greater knowledge about sexually transmitted infections and influenza, gained during the H1N1/09 public health campaign. They recognized their poverty as a risk for contracting infectious diseases, along with their inability to always employ known strategies to prevent infectious diseases, due to circumstances. They showed considerable insight into the detrimental effects of poor hygiene, sleeping locations and risk behaviour. Interviewed homeless youth regarded themselves as good compliers of health professional advice and offered valuable suggestions to improve immunization in their population. To provide effective public health interventions, it is necessary to consider the knowledge, attitudes, beliefs, and experiences of hard to reach, high risk groups. Our study shows that homeless youth are interested and capable in discussing immunization. Active targeting of homeless youth for public health immunization programs is needed. Working collaboratively with non-profit organizations that assist homeless youth provides an opportunity to increase their knowledge of infectious risks and to improve immunization strategies in this vulnerable group.
  BMC Public Health 05/2012; 12:338. · 2.00 Impact Factor
• Article: Evaluation of meningococcal serogroup C conjugate vaccine programs in Canadian children: interim analysis.

  Julie A Bettinger, David W Scheifele, Scott A Halperin, James D Kellner, Otto G Vanderkooi, Anthony Schryvers, Gaston De Serres, Joenel Alcantara
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  ABSTRACT: To assess antibody titers afforded by meningococcal C- (MenC) tetanus toxoid conjugate vaccine at 12 months of age in three different immunization schedules. This prospective study included three similar cohorts of healthy infants from 1-dose, 2-dose and 3-dose MenC infant immunization programs. Infants were enrolled at 12 months of age and given the final scheduled dose of MenC-tetanus toxoid conjugate vaccine with sera collected prior to and 1 month after the vaccination. Serum bactericidal activity (SBA) titers ≥ 1:8 were considered protective. Before the 12 month dose, participants had significantly different protective titers according to the number of prior doses received: 100% (95% CI 97.6-100%) of infants who had 2 prior doses (at 2 and 4 months) were protected compared to 84.0% (76.7-89.3%) of participants with one dose (at 2 months) and 27.6% (21.0-35.4%) of unvaccinated infants. All subjects were protected after the 12 month MenC dose, but titers were higher with prior priming. Two MenC doses given in infancy afford optimal protection during the first year of life; however, substantial protection was seen after one dose at 2 months.
  Vaccine 04/2012; 30(27):4023-7. · 3.77 Impact Factor
• Article: Human challenge studies: a review of adequacy of reporting methods and results.

  Jennifer A Kalil, Scott A Halperin, Joanne M Langley
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  ABSTRACT: Since the 1940s, researchers have purposefully infected healthy adult humans with pathogenic organisms to study how these pathogens cause disease and can be treated and prevented. 'Challenge studies' can be safe, ethical, extremely informative and an efficient use of resources during the clinical development of vaccines, but knowledge of this form of clinical research trial is not widespread. A review of the human challenge literature was performed to determine whether common elements of challenge studies can be identified in the articles published to date. The review demonstrated incomplete reporting of study characteristics deemed necessary for the correct interpretation and application of human challenge study results and for the accurate replication of study methodology. An unofficial extension of the Consolidated Standards of Reporting Trials (CONSORT) statement is proposed.
  Future Microbiology 04/2012; 7(4):481-95. · 3.82 Impact Factor
• Article: Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: a PHAC/CIHR Influenza Research Network (PCIRN) study.

  Joanne M Langley, David W Scheifele, Caroline Quach, Otto G Vanderkooi, Brian Ward, Shelly McNeil, Simon Dobson, James D Kellner, Susan Kuhn, Tobias Kollman, Donna MacKinnon-Cameron, Bruce Smith, Yan Li, Scott A Halperin
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  ABSTRACT: Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age to inform public health decision making. Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2 doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ~24 h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621. Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5°C) was more common in two-dose compared to one dose recipients (16.7%, n=4 v. 1.0%, n=2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p<0.001). At 21 days, all regulatory criteria for influenza vaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident. Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in TIV resulted in no unusual adverse effects and 100% were sero-protected for A/H1N1 after receipt of the 2010-11 TIV.
  Vaccine 03/2012; 30(23):3389-94. · 3.77 Impact Factor
• Article: Persistence of the immune response at 5 years of age following infant immunisation with investigational quadrivalent MenACWY conjugate vaccine formulations.

  Ameneh Khatami, Matthew D Snape, Elizabeth Davis, Helen Layton, Tessa John, Ly-Mee Yu, Peter M Dull, Christopher J Gill, Tatjana Odrjlin, Simon Dobson, Scott A Halperin, Joanne M Langley, Shelly A McNeil, Andrew J Pollard
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  ABSTRACT: Serogroup A, C, W-135 and Y meningococcal (MenACWY) conjugate vaccines are recommended for routine adolescent immunisation in the United States and Canada. We evaluated the persistence of bactericidal antibodies through early childhood, following infant immunisation with varying schedules of MenACWY-CRM(197) vaccine. UK and Canadian infants were immunised with 2-3 doses of MenACWY-CRM(197) or 2 doses of serogroup C meningococcal (MenC) conjugate vaccine, and either MenACWY-CRM(197), 1/5 dose of MenACWY polysaccharide vaccine or no booster at 12 months. Control groups recruited at 60 months had received country-specific infant doses of MenC conjugate vaccine. hSBA titres were measured in participants at 40 and 60 months of age. 382 children were enrolled in 12 groups (22-40 per group). By age 60 months, 3-11% of children primed and boosted with MenACWY-CRM(197) had hSBA titres≥1:8 against serogroup A, 14-45% against serogroup C, 57-85% against serogroup W-135 and 42-71% against serogroup Y. Children primed with MenC and boosted with MenACWY-CRM(197) had similar results, except for serogroup C (59%). In age-matched controls administered MenC vaccine at 2, 3, and 4 months (UK), 2 and 12 months or 12 months only (Canada), percentages with hSBA titres≥1:8 were 0-3%, 29-53%, 34-36% and 10-29% against serogroups A, C, W-135 and Y respectively. Serogroup-specific bactericidal antibody wane following infant immunisation with MenACWY-CRM(197), most markedly against serogroup A. Best persistence against serogroup C is observed with MenC conjugate vaccine priming and MenACWY-CRM(197) at 12 months, compared to schedules using only MenACWY-CRM(197), with the potential for providing broader protection compared to monovalent MenC vaccines alone.
  Vaccine 03/2012; 30(18):2831-8. · 3.77 Impact Factor
• Article: Safety and immunogenicity of 2010-2011 H1N12009-containing trivalent inactivated influenza vaccine in children 12-59 months of age previously given AS03-adjuvanted H1N12009 pandemic vaccine: A PHAC/CIHR Influenza Research Network (PCIRN) study.

  Joanne M. Langley, David W. Scheifele, Caroline Quach, Otto G. Vanderkooi, Brian J. Ward, Shelly McNeil, Simon Dobson, Jim D. Kellner, S Kuhn, Tobias Kollmann, D Mackinnon-Cameron, B Smith, Y Li, Scott A. Halperin
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  ABSTRACT: BACKGROUND: Concern arose in 2010 that reactogenicity, particularly febrile seizures, to influenza A/H1N1-containing 2010-2011 trivalent seasonal inactivated influenza vaccine (TIV) could occur in young children who had been previously immunized and/or infected with the pandemic strain. We conducted a pre-season study of 2010-2011 TIV safety and immunogenicity in children 12-59 months of age to inform public health decision making. METHODS: Children immunized with 1 or 2 doses of the pandemic vaccine, with or without the 2009-10 TIV, received 1 or 2 doses of 2010-11 TIV in an observational, multicentre Canadian study. Standard safety monitoring was enhanced by a telephone call at ∼24h post-TIV when adverse events were expected to peak. Summary safety reports were rapidly reported to public health before the launch of public programs. TIV immunogenicity was assessed day 0, and 21 days after final vaccination. Clinical Trials Registration NCT01180621. RESULTS: Among 207 children, a general adverse event was reported by 60.9% of children post-dose one and by 58.3% post-dose two. Only severe fever (>38.5°C) was more common in two-dose compared to one dose recipients (16.7%, n=4 v. 1.0%, n=2). At baseline 99.0% of participants had A/H1N1 hemagglutinin inhibition (HAI) titers ≥10, and 85.5% had a protective titer of ≥40 (95% CI 80.0, 90.0). Baseline geometric mean titers (GMT) were higher in recipients of a 2-dose schedule of pandemic vaccine compared to one-dose recipients: 153.1 (95% CI 126.2, 185.7) v. 78.8 ((58.1, 106.8, p<0.001). At 21 days, all regulatory criteria for influenza vaccine immunogenicity were exceeded for A/H1N1 and H3N2, but responses to the B antigen were poor. No correlations between reactogenicity and either baseline high influenza titers or serologic response to revaccination were evident. CONCLUSIONS: Infants and toddlers who received AS03-adjuvanted A/H1N1 2009 vaccine up to 11 months earlier retained high titers in the subsequent season but re-exposure to A/H1N1 2009 antigen in TIV resulted in no unusual adverse effects and 100% were sero-protected for A/H1N1 after receipt of the 2010-11 TIV.
  Vaccine 03/2012; · 3.77 Impact Factor
• Article: Comparison of safety and immunogenicity of two doses of investigational hepatitis B virus surface antigen co-administered with an immunostimulatory phosphorothioate oligodeoxyribonucleotide and three doses of a licensed hepatitis B vaccine in healthy adults 18-55 years of age.

  Scott A Halperin, Brian Ward, Curtis Cooper, Gerald Predy, Francisco Diaz-Mitoma, Marc Dionne, Joanne Embree, Allison McGeer, Paul Zickler, Karl-Heinz Moltz, René Martz, Ingo Meyer, Shelly McNeil, Joanne M Langley, Eduardo Martins, William L Heyward, J Tyler Martin
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  ABSTRACT: The currently licensed aluminum-hydroxide-adjuvanted hepatitis B vaccines require three doses over a 6-month period to achieve high rates of protection in adults. We compared tolerability and immunogenicity of two doses of an investigational hepatitis B vaccine using hepatitis B surface antigen adjuvanted with an immunostimulatory phosphorothioate oligodeoxyribonucleotide (HBV-ISS) to three doses of a licensed alum-adjuvanted vaccine (HBV-Eng). In this randomized, observer-blind study, healthy adults received two doses of HBV-ISS at 0 and 4 weeks or three doses of HBV-Eng at 0, 4, and 24 weeks. The primary immunogenicity endpoint was the seroprotection rate (antibody ≥ 10 mIU/mL) 8 weeks after the second dose of HBV-ISS compared to 4 weeks after the third dose of HBV-Eng. A total of 2415 participants were randomized in a ratio of 3:1 to HBV-ISS (n=1809) and HBV-Eng (n=606). The percentage of subjects exhibiting a seroprotective immune response at the primary time point was significantly higher (95.1%) for HBV-ISS than for HBV-Eng (81.1%). Superiority of the seroprotective rates for HBV-ISS was demonstrated at all time points measured. Geometric mean concentrations were also significantly higher in the HBV-ISS group at all time points measured except at week 28 (24 weeks post-second dose of HBV-ISS and 4 weeks post-third dose HBV-ISS) at which time the antibody concentrations were similar. Both vaccines were welltolerated although injection-site reactions were reported at a higher rate in HBV-ISS recipients. A short, two-dose regimen of HBV-ISS induced a superior antibody response than a three-dose regimen of a licensed hepatitis B vaccine and was well tolerated.
  Vaccine 02/2012; 30(15):2556-63. · 3.77 Impact Factor