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Vaccine. 2019 Jan 3;37(1):176-186. doi: 10.1016/j.vaccine.2018.07.023. Epub 2018 Jul 24.

Immunogenicity and safety of 11- and 12-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccines (11vPHiD-CV, 12vPHiD-CV) in infants: Results from a phase II, randomised, multicentre study.

Author information

1
Instituto Hispalense de Pediatría, C/ Manuel Siurot 45, 41013 Sevilla, Spain. Electronic address: alfonsocarmona@ihppediatria.com.
2
Department of Social Medicine, Faculty of Medicine in Hradec Králové, Charles University in Prague, Šimkova 870, 500 38 Hradec Králové, Czech Republic. Electronic address: prymula@fnhk.cz.
3
Hospital de Antequera, Avenida Poeta Muñoz Rojas, s/n, 29200 Antequera, Málaga, Spain. Electronic address: mariano.miranda@andaluciajunta.es.
4
La Fe Hospital, Avinguda de Fernando Abril Martorell, 106, 46026 Valencia, Spain. Electronic address: otero_car@gva.es.
5
Pediatric Department, Burgos Universitary Hospital, Avenida Islas Baleares, s/n, 09006 Burgos, Spain.
6
Health Care Establishment in Debica, Infectious Diseases Outpatient Clinic, ul. Krakowska 91, 39-200 Debica, Poland. Electronic address: jerzy_br@poczta.onet.pl.
7
Department of Paediatric Infectious Diseases, Wroclaw Medical University, 2-2A, Chalubinskiego, 50-368 Wroclaw, Poland. Electronic address: leszek.szenborn@umed.wroc.pl.
8
Pediatric Office Dr. Renata Ruzkova, Kladenska 53, Medicentrum 6, s.r.o., 160 00 Prague, Czech Republic. Electronic address: drruzkova@email.cz.
9
Pediatric Office Dr. Med. Michael Horn, Achenweg 1, 83471 Schönau am Königssee, Germany. Electronic address: info@drhorn.de.
10
Department of Pediatrics, Centre of Postgraduate Medical Education, ul. Marymoncka 99/103, 01-813 Warsaw, Poland. Electronic address: tjackowska@cmkp.edu.pl.
11
Department of Pediatrics, Rio Hortega University Hospital, Calle Dulzaina, 2, 47012 Valladolid, Spain. Electronic address: fcentenoma@saludcastillayleon.es.
12
GSK, Av. Fleming 20, 1300 Wavre, Belgium. Electronic address: magali.x.traskine@gsk.com.
13
GSK, Av. Fleming 20, 1300 Wavre, Belgium.
14
GSK, Av. Fleming 20, 1300 Wavre, Belgium. Electronic address: dorota.d.borys@gsk.com.

Abstract

BACKGROUND:

We assessed 2 investigational 11- and 12-valent vaccines, containing capsular polysaccharides of 10 serotypes as in the pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) and CRM197-conjugated capsular polysaccharides of serotypes 19A (11-valent) or 19A and 6A (12-valent).

METHODS:

In this phase II, partially-blind, multicentre study (NCT01204658), healthy infants were randomised (1:1:1:1) to receive 11vPHiD-CV, 12vPHiD-CV, PHiD-CV, or 13-valent CRM197-conjugate pneumococcal vaccine (PCV13), at 2, 3, and 4 (primary series), and 12-15 months of age (booster dose), co-administered with DTPa-HBV-IPV/Hib. Confirmatory objectives assessed non-inferiority of investigational vaccines to comparators (PHiD-CV for common serotypes; PCV13 for 19A and 6A), in terms of percentage of infants with pneumococcal antibody concentrations ≥0.2 μg/mL and antibody geometric mean concentrations, post-primary vaccination. Reactogenicity and safety were assessed.

RESULTS:

951 children received ≥1 primary dose, 919 a booster dose. Pre-defined immunological non-inferiority criteria were met simultaneously for 9/11 11vPHiD-CV serotypes (all except 23F and 19A) and 10/12 12vPHiD-CV serotypes (all except 19A and 6A); thus, non-inferiority objectives were reached. For each PHiD-CV serotype, percentages of children with antibody concentrations ≥0.2 µg/mL were ≥96.7% post-primary (except 6B [≥75.2%] and 23F [≥81.1%]), and ≥98.1% post-booster vaccination. For each PHiD-CV serotype except serotype 1, ≥81.0% and ≥93.9% of children had opsonophagocytic activity titres ≥8, post-primary and booster vaccination. AEs incidence was similar across all groups. SAEs were reported for 117 children (29 in the 11vPHiD-CV group, 26 in the 12vPHiD-CV group, 38 in the PHiD-CV group and 24 in the PCV13 group); 4 SAEs were considered vaccination-related. No fatal events were recorded.

CONCLUSION:

Addition of 19A and 6A CRM197-conjugates did not alter immunogenicity of the PHiD-CV conjugates; for both investigational vaccines post-booster immune responses to 10 common serotypes appeared similar to those elicited by PHiD-CV. Safety and reactogenicity profiles of the investigational vaccines were comparable to PHiD-CV. Clinical trial registry: NCT01204658.

KEYWORDS:

Immunogenicity; Infants/children; Non-inferiority; PHiD-CV; Pneumococcal conjugate vaccine; Safety

PMID:
30054160
DOI:
10.1016/j.vaccine.2018.07.023
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