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Safety and immunogenicity of a primary series and booster dose of the meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) in healthy children aged 1–9 years: two phase 2 randomised, controlled, observer-blinded studies - 20/12/22

Doi : 10.1016/S1473-3099(22)00424-8 
Helen S Marshall, ProfMD a, b, , Timo Vesikari, MD c, Peter C Richmond, MBBS d, e, Jacek Wysocki, PhD f, Leszek Szenborn, MD g, Johannes Beeslaar, MD h, Jason D Maguire, MD i, Paul Balmer, PhD j, Robert O’Neill, PhD k, Annaliesa S Anderson, PhD k, Jean-Louis Prégaldien, MS l, Roger Maansson, MS m, Han-Qing Jiang, MD i, John L Perez, MD m
a Vaccinology and Immunology Research Trials Unit, Women’s and Children’s Health Network, North Adelaide, SA, Australia 
b Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, SA, Australia 
c Nordic Research Network, Tampere, Finland 
d University of Western Australia School of Medicine, Vaccine Trials Group, Wesfarmers Centre of Vaccines and Infectious Diseases, Telethon Kids Institute, WA, Australia 
e Perth Children’s Hospital, Nedlands, WA, Australia 
f Poznań University of Medical Sciences, Poznań, Poland 
g Clinical Department of Pediatric Infectious Diseases, Wroclaw Medical University, Wroclaw, Poland 
h Pfizer Vaccine Clinical Research and Development, Hurley, UK 
i Pfizer Vaccine Clinical Research and Development, Pearl River, NY, USA 
j Pfizer Vaccine Medical Development and Scientific/Clinical Affairs, Collegeville, PA, USA 
k Pfizer Vaccine Research and Development, Pearl River, NY, USA 
l Pfizer Vaccine Clinical Research and Development, Brussels, Belgium 
m Pfizer Vaccine Clinical Research and Development, Collegeville, PA, USA 

* Correspondence to: Prof Helen S Marshall, Vaccinology and Immunology Research Trials Unit, Women’s and Children’s Health Network, North Adelaide, SA 5006, Australia Vaccinology and Immunology Research Trials Unit Women’s and Children’s Health Network North Adelaide SA 5006 Australia

Summary

Background

The meningococcal serogroup B-factor H binding protein vaccine (MenB-FHbp) is licensed for use in children aged 10 years or older for protection against invasive serogroup B meningococcal disease. Because young children are at increased risk of invasive meningococcal disease, MenB-FHbp clinical data in this population are needed.

Methods

We conducted two phase 2 randomised, controlled, observer-blinded studies including healthy toddlers (age 12−23 months) across 26 Australian, Czech, Finnish, and Polish centres, and older children (age 2−9 years) across 14 Finnish and Polish centres. Exclusion criteria included previous vaccinations against serogroup B meningococcus or hepatitis A virus (HAV), and chronic antibiotic use. Toddlers were randomly allocated (2:1) via an interactive response technology system to receive either 60 μg or 120 μg MenB-FHbp or HAV vaccine and saline (control). Older children were randomly allocated (3:1) to receive 120 μg MenB-FHbp or control, with stratification by age group (2–3 years and 4–9 years). All vaccinations were administered as three doses (0, 2, and 6 months, with only saline given at 2 months in the control group). Toddlers who received 120 μg MenB-FHbp could receive a 120 μg booster dose 24 months after the end of the primary series. The percentages of participants with serum bactericidal activity using human complement (hSBA) titres at or above the lower limit of quantification (LLOQ; all greater than the 1:4 correlate of protection) against four test strains of serogroup B meningococcus 1 month after the third dose (primary immunogenicity endpoint) were measured in the evaluable immunogenicity populations (participants who received the vaccine as randomised, had available and determinate hSBA results, and had no major protocol violations). Not all participants were tested against all strains because of serum sample volume constraints. The frequencies of reactogenicity and adverse events after each dose were recorded in the safety population (all participants who received at least one dose and had safety data available). These studies are registered with ClinicalTrials.gov (NCT02534935 and NCT02531698) and are completed.

Findings

Between Aug 31, 2015, and Aug 22, 2016, for the toddler study and between Aug 27, 2015, and March 7, 2016, for the older children study, we enrolled and randomly allocated 396 toddlers (60 μg MenB-FHbp group n=44; 120 μg MenB-FHbp group n=220; control group n=132) and 400 older children (120 μg MenB-FHbp group n=294; control group n=106). 1 month after the third dose, the proportions of participants with hSBA titres at or above the LLOQ ranged across test strains from 85·0% (95% CI 62·1−96·8; 17 of 20 participants) to 100·0% (82·4−100·0; 19 of 19) in toddlers receiving 60 μg MenB-FHbp, and from 71·6% (61·4−80·4; 68 of 95) to 100·0% (96·2−100·0; 95 of 95) in toddlers receiving 120 μg MenB-FHbp, and from 79·1% (71·2−85·6; 106 of 134) to 100·0% (97·4−100·0; 139 of 139) in children aged 2–9 years receiving 120 μg MenB-FHbp. hSBA titres peaked at 1 month after the third primary dose of MenB-FHbp and then declined over time. 24 months after the third dose in the toddler study, the proportions with hSBA titres at or above the LLOQ ranged from 0·0% (0·0−17·6; 0 of 19 participants) to 41·2% (18·4−67·1; seven of 17) in those who received 60 μg MenB-FHbp and from 3·7% (0·8−10·4; three of 81) to 22·8% (14·1−33·6; 18 of 79) in those who received 120 μg MenB-FHbp. 1 month after the booster dose in toddlers, the proportions with hSBA titres at or above the LLOQ were higher than at 1 month after the primary series. MenB-FHbp reactogenicity was mostly transient and of mild to moderate severity. Adverse event frequency was similar between the MenB-FHbp and control groups and less frequent following MenB-FHbp booster than following primary doses. Two participants from the toddler study (both from the 120 μg MenB-FHbp group) and four from the older children study (three from the 120 μg MenB-FHbp group and one from the control group) were withdrawn from the study because of adverse events.

Interpretation

MenB-FHbp was well tolerated and induced protective immune responses in a high proportion of participants. These findings support a favourable MenB-FHbp immunogenicity and reactogenicity profile in young children, a population at increased risk of adverse invasive meningococcal disease outcomes.

Funding

Pfizer.

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