Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study

doi:10.1016/S0140-6736(16)31921-3

The Lancet

Volume 388, Issue 10061, 3–9 December 2016, Pages 2775-2782

https://doi.org/10.1016/S0140-6736(16)31921-3 Get rights and content

Summary

Background

In September, 2015, the UK became the first country to introduce the multicomponent group B meningococcal (MenB) vaccine (4CMenB, Bexsero) into a publicly funded national immunisation programme. A reduced two-dose priming schedule was offered to infants at 2 months and 4 months, alongside an opportunistic catch-up for 3 month and 4 month olds. 4CMenB was predicted to protect against 73–88% of MenB strains. We aimed to assess the effectiveness and impact of 4CMenB in vaccine-eligible infants in England.

Methods

Public Health England (PHE) undertakes enhanced surveillance of meningococcal disease through a combination of clinical, public health, and laboratory reporting. Laboratory-confirmed cases of meningococcal disease are followed up with PHE local health protection teams, general practitioners, and hospital clinicians to collect demographic data, vaccination history, clinical presentation, and outcome. For cases diagnosed between Sept 1, 2015, and June 30, 2016, vaccine effectiveness was assessed using the screening method. Impact was assessed by comparing numbers of cases of MenB in vaccine-eligible children to equivalent cohorts in the previous 4 years and to cases in vaccine-ineligible children.

Findings

Coverage of 4CMenB in infants eligible for routine vaccination was high, achieving 95·5% for one dose and 88·6% for two doses by 6 months of age. Two-dose vaccine effectiveness was 82·9% (95% CI 24·1–95·2) against all MenB cases, equivalent to a vaccine effectiveness of 94·2% against the highest predicted MenB strain coverage of 88%. Compared with the prevaccine period, there was a 50% incidence rate ratio (IRR) reduction in MenB cases in the vaccine-eligible cohort (37 cases vs average 74 cases; IRR 0·50 [95% CI 0·36–0·71]; p=0·0001), irrespective of the infants’ vaccination status or predicted MenB strain coverage. Similar reductions were observed even after adjustment for disease trends in vaccine-eligible and vaccine-ineligible children.

Interpretation

The two-dose 4CMenB priming schedule was highly effective in preventing MenB disease in infants. Cases in vaccine-eligible infants halved in the first 10 months of the programme. While ongoing national surveillance will continue to monitor the longer-term impact of the programme, these findings represent a step forward in the battle against meningococcal disease and will help reassure that the vaccine protects against this deadly infection.

Funding

Public Health England.

Introduction

In September, 2015, the UK became the first country to introduce the multicomponent, protein-based meningococcal vaccine (4CMenB; Bexsero, GSK, Rixensart, Belgium) into a national, publicly funded infant immunisation programme.¹ The vaccine was offered to all infants born since July 1, 2015, at 2 months, 4 months, and 12 months alongside their routine immunisations. Catch-up vaccination was also opportunistically offered to 3 month and 4 month olds attending their routine immunisation visits, who were eligible for a 3-4-12 month and 4-12 month schedule, respectively.

Before introduction of 4CMenB, the UK immunisation schedule had included the group C meningococcal (MenC) conjugate vaccine since 1999.² As an emergency response to a national outbreak of group W meningococcal (MenW) disease, 13–18 year olds and new university entrants have been offered the quadrivalent MenACWY conjugate vaccine since August, 2015.³ These conjugate vaccines target the polysaccharide capsule of meningococci and do not offer cross-protection against other meningococcal capsular groups, such as group B (MenB), which remains responsible for most cases of invasive meningococcal disease in the UK, especially in young children.¹

Development of an effective conjugate vaccine against MenB has not been possible because its polysaccharide capsule is structurally homologous to glycoproteins in fetal neural cell adhesion molecules, making them poorly immunogenic self-antigens.⁴ 4CMenB is a novel vaccine composed of three recombinant proteins—factor H-binding protein (fHbp), Neisserial heparin-binding antigen (NHBA), and Neisserial adhesin A (NadA)—and the outer membrane vesicles (OMV) from the New Zealand outbreak strain (NZ98/254), which incorporates the immunodominant Porin A (PorA) P1.4 protein.⁵ The vaccine was licensed in Europe in January, 2013, on the basis of immunogenicity and safety studies alone. 4CMenB induces high titres of bactericidal antibodies against the target vaccine antigens but, as yet, protection against invasive disease has not been shown.

Research in context

Evidence before this study

We searched PubMed with the terms “4CMenB”, “Bexsero”, “meningococcal serogroup B vaccine”, and any combination of “vaccine effectiveness” or “impact”. Publication dates and languages were not limited. Our search results identified no data for the vaccine effectiveness or impact of 4CMenB against invasive meningococcal group B (MenB) disease.

In January, 2013, 4CMenB was licensed in Europe on immunogenicity and safety studies only. The vaccine induces bactericidal antibodies that target the respective antigens, which could be absent or variably expressed on the surface of different meningococci. Because 4CMenB contains multiple recombinant proteins in addition to the outer membrane vesicle, antibody concentrations or bactericidal activity against individual vaccine antigens do not reliably predict in-vitro killing of meningococci. For this reason, the Meningococcal Antigen Typing System (MATS) was developed to screen large numbers of meningococcal strains and predict whether they would be killed by 4CMenB-induced antibodies. MATS is a qualitative and quantitative ELISA that quantifies expression of the vaccine-associated antigens (fHbp, NHBA, and NadA) in combination with the ability of 4CMenB-induced antibodies to recognise these proteins on the surface of individual meningococcal isolates. For an isolate to be MATS positive, antibodies against at least one vaccine antigen must exceed the positive bactericidal threshold, which is assigned on the basis of killing using postvaccination sera from infants after their 12-month booster, or the isolate must possess homologous PorA (P1.4). In England and Wales, MATS predicted that 73% (95% CI 57–87%) of invasive MenB disease isolates in 2007–08 would be killed by vaccine-induced antibodies in infants. In a serum bactericidal antibody assay with human complement (hSBA), however, pooled sera from infants and adolescents immunised with 4CMenB killed 88% of a representative sample of MenB disease isolates from England and Wales during 2007–08. In the cost-effectiveness analysis, therefore, 4CMenB was predicted to protect against 73–88% of circulating MenB strains in the UK.

Compared with adolescents and adults, infants have lower cross-protection against MenB strains that are predicted by MATS to be non-vaccine preventable. Data from a recent university-associated MenB outbreak in the USA showed that sera from a third of 499 adolescents who received two doses of 4CMenB 10 weeks apart were unable to kill the outbreak strain using the hSBA assay, even though the outbreak strain was predicted by MATS to express two vaccine antigens.

Added value of this study

The UK is the first country to introduce 4CMenB into a publicly funded, national immunisation programme. In England, vaccine coverage was high in all eligible cohorts, reaching 95·5% for one dose and 88·6%% for two doses. During the first 10 months of the programme, two-dose vaccine effectiveness of 82·9% against all MenB disease was equivalent to a vaccine effectiveness of 94·2% against vaccine-preventable MenB strains. By the end of June, 2016, MenB cases in vaccine-eligible infants had halved, irrespective of the infants’ vaccination status or expected vaccine strain coverage.

Implication of all the available evidence

We have provided the first evidence of protection against group B meningococcal disease conferred by the novel, multicomponent 4CMenB vaccine in infants. While ongoing national surveillance will continue to monitor the longer-term impact of the programme, these findings represent a step forward in the battle against meningococcal disease and will help reassure that the vaccine protects against this deadly infection.

Other countries have been reluctant to introduce 4CMenB into their national programmes because of the high price of the vaccine and the low incidence of MenB, leading to unfavourable health economic assessments, as well as uncertainties around strain coverage, vaccine safety, and effectiveness.6, 7, 8, 9 In March, 2014, the UK Joint Committee on Vaccination and Immunisation (JCVI) concluded that 4CMenB could be cost-effective,¹⁰ with a reduced two-dose infant priming schedule.¹¹ After a year of negotiation with the vaccine manufacturer, an infant immunisation programme with 4CMenB was announced in March, 2015,¹² and the first infants were vaccinated on Sept 1, 2015. Here, we report the first estimates of effectiveness and the early impact of the programme in England.

Section snippets

Case ascertainment and follow-up

Public Health England (PHE) undertakes enhanced national surveillance of invasive meningococcal disease in England through a combination of clinical, public health, and laboratory reporting. The PHE Meningococcal Reference Unit (MRU) provides a national service for confirming, grouping, and characterising invasive meningococcal isolates.¹³ The MRU also provides free PCR testing of clinical samples from patients with suspected invasive meningococcal disease across England. Consequently, case

Results

In England, introduction of 4CMenB rapidly achieved high vaccine coverage; in the routine cohort, vaccine coverage by birth month ranged between 94·8–95·5% for one dose and 84·8–88·6% for two doses by 6 months of age (figure 1; appendix p 2). Coverage for the catch-up cohort born in June, 2015, was 88·8% for one dose and 75·2% for two doses, and, for the May, 2015, cohort, was 76·6% for the single dose that they were eligible for.

Between Sept 1, 2015, and June 30, 2016 (10 months), 55 cases of

Discussion

A reduced two-dose infant priming schedule of the novel, multicomponent, protein-based 4CMenB vaccine was 82·9% effective in preventing MenB disease in infants aged younger than 12 months. During the first 10 months of the programme, cases of MenB halved in vaccine-eligible infants, providing further evidence of vaccine efficacy. This measure of impact does not take into account the vaccination status of the infants or whether the infecting MenB strain was vaccine preventable. The findings are

References (25)

H Campbell et al.
Meningococcal C conjugate vaccine: the experience in England and Wales
Vaccine
(2009)
D Serruto et al.
The new multicomponent vaccine against meningococcal serogroup B, 4CMenB: immunological, functional and structural characterization of the antigens
Vaccine
(2012)
U Vogel et al.
Predicted strain coverage of a meningococcal multicomponent vaccine (4CMenB) in Europe: a qualitative and quantitative assessment
Lancet Infect Dis
(2013)
G Frosi et al.
Bactericidal antibody against a representative epidemiological meningococcal serogroup B panel confirms that MATS underestimates 4CMenB vaccine strain coverage
Vaccine
(2013)
B Brunelli et al.
Influence of sequence variability on bactericidal activity sera induced by Factor H binding protein variant 1.1
Vaccine
(2011)
K Cartwright et al.
Immunogenicity and reactogenicity in UK infants of a novel meningococcal vesicle vaccine containing multiple class 1 (PorA) outer membrane proteins
Vaccine
(1999)
SN Ladhani et al.
Enter B and W: two new meningococcal vaccine programmes launched
Arch Dis Child
(2016)
H Campbell et al.
Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015
Euro Surveill
(2015)
LK Tan et al.
Advances in the development of vaccines against Neisseria meningitidis
N Engl J Med
(2010)
M Tirani et al.
Health and economic outcomes of introducing the new MenB vaccine (Bexsero) into the Italian Routine Infant Immunisation Programme
PLoS One
(2015)

G Vernikos et al.

Bexsero(R) chronicle

Pathog Glob Health

(2014)

H Yamashiro et al.

The role of pediatricians as key stakeholders in influencing immunization policy decisions for the introduction of meningitis B vaccine in Canada: The Ontario perspective

Can J Infect Dis Med Microbiol

(2015)

Cited by (228)

Use of a meningococcal group B vaccine (4CMenB) in populations at high risk of gonorrhoea in the UK
2024, The Lancet Infectious Diseases
The meningococcal group B vaccine, 4CMenB, is a broad-spectrum, recombinant protein vaccine that is licensed for protection against meningococcal group B disease in children and adults. Over the past decade, several observational studies supported by laboratory studies have reported protection by 4CMenB against gonorrhoea, a sexually transmitted infection caused by Neisseria gonorrhoeae. Gonorrhoea is a major global public health problem, with rising numbers of diagnoses and increasing resistance to multiple antibiotics. In England, more than 82 000 cases of gonorrhoea were diagnosed in 2022, with nearly half of the cases diagnosed among gay, bisexual, and other men who have sex with men. There are currently no licensed vaccines against gonorrhoea but 4CMenB is estimated to provide 33–47% protection against gonorrhoea. On Nov 10, 2023, the UK Joint Scientific Committee on Vaccination and Immunisation agreed that a targeted programme should be initiated using 4CMenB to prevent gonorrhoea among individuals at higher risk of infection attending sexual health services in the UK. This decision was made after reviewing evidence from retrospective and prospective observational studies, laboratory and clinical data, national surveillance reports, and health economic analyses. In this Review, we summarise the epidemiology of invasive meningococcal disease and gonorrhoea in England, the evidence supporting the use of 4CMenB for protection against gonorrhoea, and the data needed to inform long-term programme planning and extension to the wider population.
Trends in laboratory-confirmed bacterial meningitis (2012–2019): national observational study, England
2023, The Lancet Regional Health - Europe
Bacterial meningitis is associated with significant morbidity and mortality worldwide. We aimed to describe the epidemiology, aetiology, trends over time and outcomes of laboratory-confirmed bacterial meningitis in England during 2012–2019.
UK Health Security Agency routinely receives electronic notifications of confirmed infections from National Health Service hospital laboratories in England. Data were extracted for positive bacterial cultures, PCR-positive results for Neisseria meningitidis or Streptococcus pneumoniae from cerebrospinal fluid and positive blood cultures in patients with clinical meningitis.
During 2012–19, there were 6554 laboratory-confirmed cases. Mean annual incidence was 1.49/100,000, which remained stable throughout the surveillance period (p = 0.745). There were 155 different bacterial species identified, including 68.4% (106/1550) Gram-negative and 31.6% (49/155) Gram-positive bacteria. After excluding coagulase-negative staphylococci (2481/6554, 37.9%), the main pathogens causing meningitis were Streptococcus pneumoniae (811/4073, 19.9%), Neisseria meningitidis (497/4073, 12.2%), Staphylococcus aureus (467/4073, 11.5%), Escherichia coli (314/4073, 7.7%) and group B streptococcus (268/4073, 6.6%). Pneumococcal meningitis incidence increased significantly during 2012–9, while meningococcal, group A streptococcal and tuberculous meningitis declined. Infants aged <3 months had the highest mean incidence (55.6/100,000; 95% CI, 47.7–63.5) driven mainly by group B streptococci, followed by 3–11 month-olds (8.1/100,000; 95% CI 7.1–9.0), where pneumococcal and meningitis predominated. The 30-day case-fatality rate (CFR) was 10.0% (71/6554). Group A streptococcal meningitis had the highest CFR (47/85, 55.3%). The probability of surviving at 30 days was 95.3% (95% CI, 93.4–97.3%) for infants and 80.0% for older adults (77–84%).
The incidence of bacterial meningitis has remained stable. The high CFR highlights a need for prevention through vaccination.
PHE.
4CMenB sustained vaccine effectiveness against invasive meningococcal B disease and gonorrhoea at three years post programme implementation
2023, Journal of Infection
To evaluate persistence of vaccine effectiveness (VE) and vaccine impact (VI) on invasive meningococcal B (MenB) disease and gonorrhoea at three years after implementation of a state funded 4CMenB programme for infants, children, adolescents and young people in South Australia.
VI was assessed using a Poisson or negative binomial regression model, and VE was estimated using screening and case-control methods. Chlamydia controls were used to estimate VE in the primary analysis to control potential confounding effects such as high-risk sexual behaviour associated with sexually transmitted infections.
During the three-year programme, reductions of 63.1% (95%CI 29.0–80.9%) and 78.5% (95%CI 33.0–93.1%) in incidence of MenB disease were observed in infants and adolescents, respectively. There were no cases in infants who had received three doses of 4CMenB. Two-dose VE against MenB disease was 90.7% (95%CI 6.9–99.1%) for the childhood programme and 83.5% (95%CI 0–98.2%) for the adolescent programme. Two-dose VE against gonorrhoea in adolescents was 33.2% (95%CI 15.9–47.0%). Lower VE estimates were demonstrated after 36 months post-vaccination (23.2% (95%CI 0–47.5%)> 36 months post-vaccination compared to 34.9% (95%CI 15.0–50.1%) within 6–36 months). Higher VE estimates were found after excluding patients with repeat gonorrhoea infections (37.3%, 95%CI 19.8–51.0%). For gonorrhoea cases co-infected with chlamydia VE was maintained (44.7% (95%CI 17.1–63.1%).
The third-year evaluation results show persistent vaccine effectiveness of 4CMenB against MenB disease in infants and adolescents. As this is the first ongoing programme for adolescents, moderate vaccine protection against gonorrhoea with waning effectiveness three years post-vaccination was demonstrated in adolescents and young adults. The additional protection of 4CMenB vaccine against gonorrhoea, likely through cross-protection should be considered in cost-effectiveness analyses. A booster dose may need to be further evaluated and considered in adolescents due to waning protection against gonorrhoea demonstrated after 36 months post-vaccination.
Challenges in synthesis of real-world vaccine effects on meningococcal serogroup B disease for 4CMenB vaccine post-licensure effectiveness studies: A systematic review
2023, Vaccine
Real-world studies on vaccine effects are diverse in terms of objectives, study setting and design, data type and scope, and analysis methods. In this review, we describe and discuss four-component meningococcal serogroup B vaccine (4CMenB vaccine, Bexsero) real-world studies with the aim of synthesizing their findings with application of standard methods.
We performed a systematic literature review of all real-world studies on 4CMenB vaccine effects on meningococcal serogroup B disease, with no restriction for population age, vaccination schedule and/or type of vaccine effect evaluated (vaccine effectiveness [VE] and vaccine impact [VI] outcomes) published since its licensure in 2013 (from January 2014 until July 2021) in PubMed, Cochrane and the grey literature. We then aimed to synthesize the findings of the identified studies through application of standard synthesis methods.
According to reported criteria we retrieved five studies presenting estimates on 4CMenB vaccine effectiveness and impact. These studies showed great diversity in population, vaccination schedule and analysis methods mainly due to diversity in vaccine strategies and recommendations in the study settings. Directed by this diversity, no quantitative pooling methods to synthesize findings could be applied; instead we descriptively assessed study methods. We report VE estimates ranging from 59% to 94% and VI estimates ranging from 31% to 75%, representing diverse age groups, vaccination schedules and analysis methods.
Both vaccine outcomes showed real-life effectiveness of 4CMenB vaccine despite differences in study methodologies and vaccination strategies. Based on appraisal of study methods, we highlighted the need for an adapted tool which facilitates synthesis of heterogenic real-world vaccine studies when quantitative pooling methods are not applicable.
Effectiveness of one dose of MVA–BN smallpox vaccine against mpox in England using the case-coverage method: an observational study
2023, The Lancet Infectious Diseases
The UK experienced a national outbreak of mpox (formerly known as monkeypox) disease that started in May, 2022, as did many other countries worldwide, with case numbers rising rapidly, mainly among gay, bisexual, and other men who have sex with men (GBMSM). To control the outbreak, Modified Vaccinia Ankara–Bavaria Nordic (MVA–BN), an attenuated smallpox vaccine, was offered to at-risk GBMSM. We aimed to assess the effectiveness of a single MVA–BN dose against symptomatic mpox disease in at-risk GBMSM.
In this case-coverage study, mpox cases in England were sent questionnaires collecting information on demographics, vaccination history, symptoms, and sexual orientation. Returned questionnaires were linked to laboratory data and a public health case management system (HP Zone) to obtain additional information on symptom onset and specimen date. Cases with a rash onset date (or alternative proxy) between July 4 and Oct 9, 2022, were included. Females, heterosexual men, and those with missing vaccination information were excluded. Vaccine effectiveness was calculated using the case-coverage method in which vaccine coverage among cases is compared with coverage in the eligible population, estimated from doses given to GBMSM and the estimated size of at-risk GBMSM. Sensitivity analyses included an increase and decrease of 20% differences in the estimated high-risk GBMSM population size.
By Nov 3, 2022, 1102 people had responded to questionnaires, of which 739 were excluded (52 females or self-declared male heterosexuals, 590 with an index date outside of the study period, and 97 missing a vaccination date). 363 cases were included in the analyses. Vaccine uptake among eligible GBMSM increased steadily from July, 2022, reaching 47% by Oct 9, 2022. Of the 363 confirmed cases, eight cases either did occur or were likely to have occurred at least 14 days after vaccination, 32 within 0–13 days after vaccination, and the rest were unvaccinated. The estimated vaccine effectiveness against symptomatic mpox at least 14 days after a single dose was 78% (95% CI 54 to 89) ranging from 71 to 85 in sensitivity analyses. Vaccine effectiveness within 0–13 days after vaccination was –4% (95% CI –50 to 29).
A single MVA–BN dose was highly protective against symptomatic mpox disease among at-risk GBMSM, making it a useful tool for mpox outbreak control when rapid protection is needed. For cases in which numbers at highest risk of infection exceed vaccine supply, there might be benefit in prioritising delivery of first doses.
UK Health Security Agency.
Outcomes of meningococcal serogroup B disease in children after implementation of routine infant 4CMenB vaccination in England: an active, prospective, national surveillance study
2023, The Lancet Child and Adolescent Health
In 2015, the UK included 4CMenB, a multi-component, recombinant protein-based vaccine against meningococcal serogroup B (MenB) disease, in the national infant immunisation programme. We aimed to assess the effect of 4CMenB vaccination on the severity of MenB disease presentation and outcomes.
In this active, prospective, national surveillance study, we used data from the UK Health Security Agency national surveillance of meningococcal disease. We included data from follow-up of children younger than 5 years with laboratory-confirmed MenB disease who were eligible for 4CMenB vaccination with general practice 3–6 months after disease onset. All invasive MenB isolates were tested using the Meningococcal Antigen Typing System to determine whether the isolate was potentially preventable by 4CMenB. Admission to intensive care, death, and, when possible, reported sequelae in survivors were reviewed alongside vaccine status. For the epidemiological analysis, we compared laboratory-confirmed MenB disease cases before 4CMenB implementation (Sept 1, 2010, to March 31, 2015) with those after implementation (Sept 1, 2015, to March 31, 2020). For clinical follow-up and outcomes, we included all children younger than 5 years with laboratory-confirmed MenB disease between Sept 1, 2015, and March 31, 2021.
Between Sept 1, 2015, and March 31, 2021, there were 371 cases of MenB disease in children younger than 5 years, including 256 (69%) in those younger than 1 year and 128 (35%) in those younger than 3 months. After the introduction of 4CMenB, the peak age of patients with MenB disease shifted from 5–6 months to 1–3 months. Overall, 108 (29%) of 371 children were too young for vaccination, unvaccinated, or developed MenB disease within 14 days of the first dose. Of 110 meningococcal strains characterised, 11 (92%) of 12 were potentially preventable by 4CMenB in unvaccinated children compared with 53 (66%) of 80 in partly vaccinated and 11 (69%) of 16 in fully vaccinated children. 78 (21%) of 371 children required intensive care, and the case fatality ratio was 5% (17 of 371), with 11 of 17 deaths occurring before 1 year of age, including seven in infants who were too young (<8 weeks) for vaccination. Of 354 survivors, 57 (16%) had 74 sequelae reported; 45 (61%) of 74 were neurological, 17 (23%) were physical, two (3%) were behavioural or psychological, and ten (14%) were other complications. Prevalence of sequelae was similar in unvaccinated (15 [15%] of 98) and vaccinated (42 [16%] 256) children, as were composite outcomes of death or sequelae, and intensive care or death or sequelae.
Cases of MenB disease in vaccine-eligible children declined after 4CMenB implementation, but morbidity in vaccinated and unvaccinated children remained unchanged, highlighting the importance of vaccination to prevent MenB disease. The lower peak age of infants with MenB disease after 4CMenB implementation, with a higher case fatality ratio in young infants, highlights the importance of timely vaccination.
UK Health Security Agency.

View all citing articles on Scopus

View full text

ArticlesEffectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Case ascertainment and follow-up

Results

Discussion

Vaccine

Vaccine

Lancet Infect Dis

Vaccine

Vaccine

Vaccine

Enter B and W: two new meningococcal vaccine programmes launched

Arch Dis Child

Targeted vaccination of teenagers following continued rapid endemic expansion of a single meningococcal group W clone (sequence type 11 clonal complex), United Kingdom 2015

Euro Surveill

Advances in the development of vaccines against Neisseria meningitidis

N Engl J Med

Health and economic outcomes of introducing the new MenB vaccine (Bexsero) into the Italian Routine Infant Immunisation Programme

PLoS One

Bexsero(R) chronicle

Pathog Glob Health

The role of pediatricians as key stakeholders in influencing immunization policy decisions for the introduction of meningitis B vaccine in Canada: The Ontario perspective

Can J Infect Dis Med Microbiol

Articles
Effectiveness and impact of a reduced infant schedule of 4CMenB vaccine against group B meningococcal disease in England: a national observational cohort study