Safety and immunogenicity of the Cuban heptavalent pneumococcal conjugate vaccine in healthy infants. Results from a double-blind randomized control trial Phase I

Carlos P Dotres Martínez; Nivaldo Linares-Pérez; María E Toledo-Romaní; Yarisset Ricardo Delgado; Rinaldo Puga Gómez; Beatriz Paredes Moreno; Laura M Rodriguez-Noda; Mayelín Mirabal Sosa; Darielys Santana Mederos; Dagmar García-Rivera; Yury Valdés-Balbín; David Goldblatt; Vicente Vérez-Bencomo; Havana-Pneumococci Clinical Group; Finlay-Pneumococci Project

doi:10.1016/j.vaccine.2018.05.027

Safety and immunogenicity of the Cuban heptavalent pneumococcal conjugate vaccine in healthy infants. Results from a double-blind randomized control trial Phase I

Vaccine. 2018 Aug 6;36(32 Pt B):4944-4951. doi: 10.1016/j.vaccine.2018.05.027. Epub 2018 Jul 10.

Authors

Carlos P Dotres Martínez¹, Nivaldo Linares-Pérez², María E Toledo-Romaní³, Yarisset Ricardo Delgado⁴, Rinaldo Puga Gómez⁵, Beatriz Paredes Moreno⁶, Laura M Rodriguez-Noda⁷, Mayelín Mirabal Sosa⁸, Darielys Santana Mederos⁹, Dagmar García-Rivera¹⁰, Yury Valdés-Balbín¹¹, David Goldblatt¹², Vicente Vérez-Bencomo¹³; Havana-Pneumococci Clinical Group; Finlay-Pneumococci Project

Collaborators

Carmen R Ruiz¹⁴, Yarmila García¹⁴, Rafael Del Valle-Rodríguez¹⁴, Ada Rodríguez-Concepción¹⁴, Dania Vega¹⁴, María E Mesa¹⁴, José A Broche¹⁴, Amarilis Pérez¹⁵, Vladimir Echemendía¹⁵, Marisel Martínez¹⁵, Pablo Cabrera¹⁵, Nayibi Nuñez¹⁵, Annaliet Iglesias¹⁵, Yanet Rodríguez¹⁵, Nadezhda González¹⁵, Marlene Armesto¹⁵, Alina Álvarez¹⁵

Affiliations

¹ Children University Hospital "Juan Manuel Márquez", Marianao, Havana 11400, Cuba. Electronic address: carlos.dotres@nauta.cu.
² Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: nlinares@finlay.edu.cu.
³ Tropical Medicine Institute "Pedro Kourí", Havana, Cuba. Electronic address: mariaeugenia@ipk.edu.cu.
⁴ University Hospital "Juan Manuel Márquez", Marianao, Havana, Cuba. Electronic address: yariricardo@infomed.sld.cu.
⁵ Children University Hospital "Juan Manuel Márquez", Marianao, Havana 11400, Cuba. Electronic address: puga@infomed.sld.cu.
⁶ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: bparedes@finlay.edu.cu.
⁷ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: lmrodriguez@finlay.edu.cu.
⁸ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: mmirabal@finlay.edu.cu.
⁹ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: dsantana@finlay.edu.cu.
¹⁰ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: dagarcia@finlay.edu.cu.
¹¹ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: yvbalbin@finlay.edu.cu.
¹² World Health Organization (WHO) Pneumococcal Serology Reference Laboratory, University College London, Institute of Child Health, London, United Kingdom. Electronic address: d.goldblatt@ucl.ac.uk.
¹³ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba. Electronic address: vicente.verez@finlay.edu.cu.
¹⁴ Children University Hospital "Juan Manuel Márquez", Marianao, Havana 11400, Cuba.
¹⁵ Finlay Vaccine Institute, 200 and 21 Street, Playa, Havana 11600, Cuba.

PMID: 30005948
DOI: 10.1016/j.vaccine.2018.05.027

Abstract

Background: Cuba has a new pneumococcal conjugate vaccine candidate (PCV7-TT). This study evaluates the safety and immunogenicity in healthy infants using 2p+1 vaccination schedule.

Methods: A phase I, controlled, randomized and double blind clinical trial was designed. 30 unvaccinated healthy infants were included. 20 subjects were assigned to study group (PCV7-TT) and 10 to control group (Synflorix®) to receive the vaccines at 7, 8 months of age (primary series) and 11 months (booster dose). Blood samples were collected 30 days after second dose and post booster for antibodies measure analysis by ELISA and OPA. The statistics analysis included the frequency of occurrence for adverse events and the immune response. Non-parametric tests were used to compare the immune response. The clinical trial was published in the Cuban Public Register of Clinical Trials with code RPCEC00000173 available at http://registroclinico.sld.cu.

Results: Overall, the safety profile of PCV7-TT was similar to Synflorix®. Local reactions were predominant and systemic events were mild in severity. Swelling and redness were frequently associated with PCV7-TT mainly after the first dose (50% and 40% respectively). 15% and 10% of subject reported severe swelling after first dose with PCV7-TT and after second dose with Synflorix®. Mild fever (≥38-≤39), vomiting and sleep disturb were the systemic events reported. 100% of infants achieved pneumococcal IgG antibody concentrations ≥0.35 µg/ml after booster dose for serotypes 1, 14, 18C and 19F in each vaccine group. For serotypes 5, 6B and 23F, more than 80% infants vaccinated with Synflorix® or PCV7-TT achieved protective IgG GMC ≥ 0.35 µg/ml after booster dose. OPA proportion's responders to the seven common serotypes were 89.5% or more after the primary dose and 100% after booster dose in vaccinated with PCV7-TT.

Conclusions: The Cuban PCV7-TT is safe, well tolerated and immunogenic in healthy infants.

Keywords: Clinical trial; Cuban; Immunogenicity; Infant; Pneumococcal conjugate vaccine; Safety.

Publication types

Clinical Trial, Phase I
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Bacterial / immunology
Double-Blind Method
Female
Heptavalent Pneumococcal Conjugate Vaccine / administration & dosage
Heptavalent Pneumococcal Conjugate Vaccine / therapeutic use*
Humans
Immunization Schedule
Infant
Male
Pneumococcal Infections / immunology
Pneumococcal Infections / prevention & control*
Vaccines, Conjugate / administration & dosage
Vaccines, Conjugate / therapeutic use*

Substances

Antibodies, Bacterial
Heptavalent Pneumococcal Conjugate Vaccine
Vaccines, Conjugate