Global epidemiology of serogroup B meningococcal disease and opportunities for prevention with novel recombinant protein vaccines

Background: Meningococcal disease (MD) is a major cause of meningitis and sepsis worldwide, with a high case fatality rate and frequent sequelae. Neisseria meningitidis serogroups A, B, C, W, X and Y are responsible for most of these life-threatening infections, and its unpredictable epidemiology can cause outbreaks in communities, with significant health, social and economic impact. Currently, serogroup B is the main cause of MD in Europe and North America and one of the most prevalent serogroups in Latin America. Mass vaccination strategies using polysaccharide vaccines have been deployed since the 1970s and the use of conjugate vaccines has controlled endemic and epidemic disease caused by serogroups A, C, W and Y and more recently serogroup B using geographically-specific outer membrane vesicle based vaccines. Two novel protein-based vaccines are a significant addition to our armamentarium against N. meningitidis as they provide broad coverage against highly diverse strains in serogroup B and other groups. Early safety, effectiveness and impact data of these vaccines are encouraging. These novel serogroup B vaccines should be actively considered for individuals at increased risk of disease and to control serogroup B outbreaks occurring in institutions or specific regions, as they are likely to save lives and prevent severe sequelae. Incorporation into national programs will require thorough country-specific analysis

Identifying the research, advocacy, policy and implementation needs for the prevention and management of respiratory syncytial virus lower respiratory tract infection in low- and middle-income countries

Introduction: The high burden of respiratory syncytial virus (RSV) infection in young children disproportionately occurs in low- and middle-income countries (LMICs). The PROUD (Preventing RespiratOry syncytial virUs in unDerdeveloped countries) Taskforce of 24 RSV worldwide experts assessed key needs for RSV prevention in LMICs, including vaccine and newer preventive measures. Methods: A global, survey-based study was undertaken in 2021. An online questionnaire was developed following three meetings of the Taskforce panellists wherein factors related to RSV infection, its prevention and management were identified using iterative questioning. Each factor was scored, by non-panellists interested in RSV, on a scale of zero (very-low-relevance) to 100 (very-high-relevance) within two scenarios: (1) Current and (2) Future expectations for RSV management. Results: Ninety questionnaires were completed: 70 by respondents (71.4% physicians; 27.1% researchers/scientists) from 16 LMICs and 20 from nine high-income (HI) countries (90.0% physicians; 5.0% researchers/scientists), as a reference group. Within LMICs, RSV awareness was perceived to be low, and management was not prioritised. Of the 100 factors scored, those related to improved diagnosis particularly access to affordable point-of-care diagnostics, disease burden data generation, clinical and general education, prompt access to new interventions, and engagement with policymakers/payers were identified of paramount importance. There was a strong need for clinical education and local data generation in the lowest economies, whereas upper-middle income countries were more closely aligned with HI countries in terms of current RSV service provision. Conclusion: Seven key actions for improving RSV prevention and management in LMICs are proposed

Safety and immunogenicity of co-administered meningococcal serogroup B (4CMenB) vaccine: A literature review

The four-component meningococcal serogroup B vaccine (4CMenB) is indicated for the prevention of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup B. Co-administering 4CMenB with other vaccines may improve vaccine uptake provided that the safety and immunogenicity of either are not affected. Published literature on the immunogenicity and reactogenicity of 4CMenB co-administered with other routine childhood and adulthood vaccines was reviewed. From 282 publications identified, data were collated from 10 clinical studies, 3 real-world studies, and 3 reviews. The evidence showed that 4CMenB co-administration is not associated with significant safety concerns or clinically relevant immunological interferences. The increased reactogenicity (e.g., fever) associated with 4CMenB co-administration can be adequately managed with prophylactic paracetamol in children. Thus, 4CMenB co-administration has the potential to maximize vaccine coverage and improve protection against IMD globally

Immunogenicity and safety of concomitant administration of meningococcal serogroup B (4CMenB) and serogroup C (MenC-CRM) vaccines in infants: A phase 3b, randomized controlled trial

Background: After implementation of routine infant MenC vaccination, MenB remains a serious cause of meningococcal disease, yet to be targeted by vaccination programs in several countries. This study (NCT01339923) investigated the immunogenicity and safety of MenC CRM-conjugated vaccine (MenC-CRM) concomitantly administered with MenB vaccine (4CMenB). Methods: Infants (N = 251) were randomised 1:1 to receive 4CMenB and MenC-CRM (Group 1) or MenC-CRM alone (Group 2) at 3 and 5 months (M3, M5) and a booster at 12 months of age (M12), and pneumococcal vaccine at M3, M5, M7, M12. Antibody responses to meningococcal vaccines were measured at M3, M6, M12, and M13. Non-inferiority of MenC-CRM response in Group 1 vs Group 2 was demonstrated at M6 and M13, if the lower limit of the 95% confidence interval (LL95%CI) of the difference in percentage of infants with hSBA titres >= 1:8 was >-10%. Sufficiency of MenB response was achieved if LL95% CI of the percentage of infants with hSBA titres >= 1:4 against fHbp, NadA and PorA strains was >= 70% at M6 or >= 75% at M13. Adverse events (AEs) were collected for 7 days post-vaccination, and serious AEs (SAEs) and medically attended AEs throughout the study. Results: Non-inferiority of MenC response in Group 1 vs Group 2 (LL95%Cl -6.4% [M6]-5.2% [M13]) and sufficiency of MenB response in Group 1 (LL95%Cl 92%, 90%, 89% [M6]97%, 92%, 93% [M13] against fHbp, NadA, PorA, respectively) were demonstrated. Higher rates of mild to moderate solicited AEs were reported in Group 1. Unsolicited AEs and SAEs incidences were similar across groups. Conclusions: Concomitant administration of MenC-CRM and 4CMenB in infants was immunogenic, resulting in non-inferior responses against MenC compared to MenC-CRM alone and demonstration of sufficient immune response to MenB, after primary and booster vaccination. Reactogenicity was higher for concomitant vaccines administration, but no safety concerns were identified. (C) 2017 The Authors. Published by Elsevier Ltd.GlaxoSmithKline Biologicals SASanta Casa Sao Paulo Sch Med Sci, Sao Paulo, BrazilCDEC, Sao Paulo, BrazilHosp Clin Univ Santiago de Compostela, Santiago De Compostela, SpainUniv Fed Sao Paulo, CRIE UNIFESP, Sao Paulo, BrazilBrazilian Minist Hlth, CPEC, Assoc Obras Sociais Irma Dulce & Oswaldo Cruz Fdn, Salvador, BA, BrazilInst Med Integral Prof Fernando Figueira, Boa Vista Recife, PE, BrazilGSK, Amsterdam, NetherlandsGSK, Siena, ItalyCovance Neurosci Med & Sci Serv, Rome, ItalyUniv Fed Sao Paulo, CRIE UNIFESP, Sao Paulo, BrazilWeb of Scienc

Antibody persistence after serogroup C meningococcal conjugate vaccine in children with sickle cell disease

Background: A decline of protective antibody titers after MCC vaccine has been demonstrated in healthy children, this may be an issue of concern for risk groups. The aim of this study was to evaluate the persistence of bactericidal antibodies after MCC vaccine in sickle cell disease (SCD) patients. The type of vaccine used and booster response were also analyzed. Methods: SCD patients (n = 141) previously immunized with MCC vaccines had blood drawn 2-8 years after the last priming dose. They were distributed according to age at primary immunization into groups: = 8. Subjects with rSBA = 8 was demonstrated in 53.3%, 21.7% and 35.0%, 2-3, 4-5, 6-8 years, respectively, after vaccination, compared with 70.0%, 45.0% and 53.5%, respectively, for individuals primed at ages 2-13 years. rSBA median titers and IgG median levels were higher in the older group. Six to eight years after vaccination the percentage of patients with rSBA titers >= 8 was significantly higher in the group primed with MCC-TT (78.5%) compared with those primed with MCC-CRM197 [Menjugate (R) (33.3%) or Meningitec (R) (35.7%)] (p = 0.033). After a booster, 98% achieved rSBA titer >= 8. Conclusion: Immunity to meningococcal serogroup C in SCD children declines rapidly after vaccination and is dependent on the age at priming. Booster doses are needed to maintain protection in SCD patients. Persistence of antibodies seems to be longer in individuals primed with MCC-TT vaccine comparing to those immunized with MCC-CRM197. (C) 2016 Elsevier Ltd. All rights reserved.Global Infectious Diseases Research and Training Program (Fogarty International Center-National Institutes of Health) [D43TWW006592]Fundacao de Apoio a Universidade Federal de Sao Paulo (FAP)Univ Fed Sao Paulo, Dept Pediat, Pediat Infect Dis Discipline, Sao Paulo, SP, BrazilSanta Casa Sao Paulo Sch Med Sci, Dept Pediat, Sao Paulo, SP, BrazilUniv Sao Paulo, Sch Med, Infect Dis Dept, BR-05508 Sao Paulo, SP, BrazilUniv Sao Paulo, Sch Med, Dept Pathol, BR-05508 Sao Paulo, SP, BrazilManchester Royal Infirm, Manchester Lab, Publ Hlth England, Vaccine Evaluat Unit, Manchester, Lancs, EnglandUniv Fed Sao Paulo, Dept Pediat, Pediat Infect Dis Discipline, Sao Paulo, SP, BrazilNIH: D43TWW006592Web of Scienc

Reduced schedules of 4CMenB vaccine in infants and catch-up series in children: Immunogenicity and safety results from a randomised open-label phase 3b trial

Background: This study evaluated the immunogenicity and safety of a licensed meningococcal serogroup B vaccine (4CMenB) administered alone according to reduced schedules in infants or catch-up series in children. Methods: In this open-label, multicentre, phase 3b study (NCT01339923), infants randomised 1:1:1 received 4CMenB: 2 + 1 doses at 31/2-5-11 months or 6-8-11 months of age, 3 + 1 doses at ages 21/2-3 1/2-5-11 months. Children aged 2-10 years received 2 catch-up doses administered 2 months apart. Immune responses were measured by hSBA assays against 4 strains specific for vaccine components fHbp, NadA, PorA and NHBA. Sufficiency of immune responses was defined in groups with 2 + 1 doses schedules as a lower limit >= 70% for the 97.5% confidence interval of the percentage of infants with hSBA titres >= 4, 1 month post-dose 2 for fHbp, NadA, PorA. Adverse events were collected for 7 days post -vaccinationserious adverse events (SAEs) throughout the study. Results: 754 infants and 404 children were enrolled. Post-primary vaccination, 98-100% of infants across all groups developed hSBA titres >= 4 for fHbp, NadA, PorA, and 48-77% for NHBA. Sufficiency of immune responses in infants receiving 2 + 1 schedules was demonstrated for fHbp, NadA, PorA after 2 doses of 4CMenB, as pre-specified criteria were met. Following receipt of 2 catch-up doses, 95-99% of children developed hSBA titres >= 4 for 4CMenB components. Similar safety profiles were observed across groups. A total of 45 SAEs were reported, 3 of which were related to vaccination. Conclusion: Reduced infant schedules and catch-up series in children were immunogenic and safe, having the potential to widen 4CMenB vaccine coverage. Funding: GlaxoSmithKline Biologicals SA. (C) 2017 Published by Elsevier Ltd.Hosp Clin Univ Santiago de Compostela, Dept Pediat, Translat Pediat & Infect Dis, A Choupana,S-N, Santiago De Compostela 15706, SpainSanta Casa Sao Paulo Sch Med Sci, Rua Doutor Cesario Motto Jr,61 Vila Buarque, BR-01221020 Sao Paulo, BrazilInst Hispalense Pediat Sevilla, Ave Manuel Siurot 45, Seville 41013, SpainHosp Virgen Mar, Carretera Mami Viator, Almeria, SpainHosp Univ Mostoles, Rio Jacar S-N, Madrid 28935, SpainUniv Fed Sao Paulo, CRIE UNIFESP, R Sena Madureira,1500 Vila Clementino, BR-04021001 Sao Paulo, BrazilCPEC Assoc Obras Sociais Irma Dulce, Salvador, BA, BrazilBrazilian Minist Hlth, Oswaldo Cruz Fdn, Salvador, BA, BrazilGSK, Huis Ter Heideweg 62, NL-3705 LZ Amsterdam, NetherlandsGSK, Via Fiorentina 1, I-53100 Siena, ItalyCovance Inc, Rome, ItalyUniv Fed Sao Paulo, CRIE UNIFESP, R Sena Madureira,1500 Vila Clementino, BR-04021001 Sao Paulo, BrazilWeb of Scienc

Pandemic’s influence on parents’ attitudes and behaviors toward meningococcal vaccination

Invasive meningococcal disease is a life-threatening infection preventable through vaccination. Pediatric vaccination rates have declined during the coronavirus disease 2019 (COVID-19) pandemic. This survey aimed to understand how parents’ attitudes and behaviors have changed during the pandemic with regard to immunization and, more specifically, meningococcal vaccination. An online survey was emailed to parents of eligible children 0–4 years, following the selection process from UK, France, Germany, Italy, Brazil, Argentina, and Australia; and of adolescents 11–18 years from US. Data collection took place 19 January–16 February 2021. Quotas were set to ensure a representative sample. Eleven questions relating to general perceptions around vaccination and attitudes and behaviors toward meningitis vaccination were displayed. On 4,962 parents (average 35 years) participating in the survey, most (83%) believed important for their child to continue receiving recommended vaccines during the COVID-19 pandemic. Nearly half of routine vaccine appointments were delayed or canceled due to the pandemic, and 61% of respondents were likely to have their children catch up once COVID-19 restrictions were lifted. 30% of meningitidis vaccination appointments were canceled or delayed during the pandemic, and 21% of parents did not intend to reschedule them because of lockdown/stay at home regulations, and fear of catching COVID-19 in public places. It is crucial to communicate clear instructions to health workers and the general population and to provide appropriate safety precautions in vaccination centers. This will help to maintain vaccination rates and limit infections to prevent future outbreaks

Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

Background: Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods: The epidemiology of respiratory viruses among healthy children (6 months to < 10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results: 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medicallyattended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/ enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions: Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children. (C) 2016 Published by Elsevier Ltd on behalf of The British Infection Association.GlaxoSmithKline Biologicals S.AGSK Vaccines, 20 Ave Fleming, B-1330 Wavre, BelgiumCtr Estudios Infectol Pediat, Cali, ColombiaUniv Fed Sao Paulo, Dept Pediat, Pediat Infect Dis, Sao Paulo, BrazilRes Inst Trop Med, Dept Hlth, Muntinlupa, PhilippinesInst Costarricense Invest Clin, San Jose, Costa RicaNatl Inst Publ Hlth Mexico, Cuernavaca, Morelos, MexicoPhramongkutklao Hosp, Dept Pediat, Infect Dis Unit, Bangkok, ThailandInst Nacl Pediat Mexico, Mexico City, DF, MexicoUniv Autonoma Nuevo Leon, Med Serv, Monterrey, MexicoHosp Gen Durango, Durango, MexicoFac Ciencias Med Santa Casa Sao Paulo, Sao Paulo, BrazilAssoc Fundo Incent Pesquisa, Dept Pediat, Sao Paulo, BrazilNatl Univ Singapore, Natl Healthcare Grp Polyclin, Singapore, SingaporeGSK Vaccines, King Of Prussia, PA USAUniv Melbourne, Murdoch Childrens Res Inst, Carlton, Vic, AustraliaUniv Melbourne, Melbourne Sch Populat & Global Hlth, Carlton, Vic, AustraliaPediatric Infectious Diseases, Department of Pediatrics, Universidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc