Open Access Research article

Extended antigen sparing potential of AS03-adjuvanted pandemic H1N1 vaccines in children, and immunological equivalence of two formulations of AS03-adjuvanted H1N1 vaccines: results from two randomised trials

Odile Launay1132*, Xavier Duval3, Serge Fitoussi4, Wolfgang Jilg5, Angkool Kerdpanich6, May Montellano7, Tino F Schwarz8, Veerachai Watanveerade6, Jürgen J Wenzel5, Gerard Zalcman9, Vinod Bambure10, Ping Li11, Adrian Caplanusi12, Anuradha Madan11, Paul Gillard12 and David W Vaughn11

Author Affiliations

1 Inserm, CIC BT505; Assistance Publique-Hôpitaux de Paris, Groupe Hospitalier Cochin Broca Hôtel-Dieu, CIC de vaccinologie Cochin Pasteur; Université Paris Descartes, Paris, France

2 The National clinical vaccine research network (REIVAC), Paris, France

3 C.I.C Bichat, Paris, France

4 Mediscis, Poitiers, France

5 Institute of Medical Microbiology and Hygiene, University of Regensburg, Regensburg, Germany

6 Infectious Diseases Unit, Department of Pediatrics, Phramongkutklao Hospital, Bangkok, Thailand

7 Department of Pediatrics, Mary Chiles General Hospital, Manila, Philippines

8 Central Laboratory and Vaccination Centre, StiftungJuliusspital, Würzburg, Germany

9 Caen University Hospital – Early Phase Research Center/Centre de Recherche Clinique, Caen, France

10 GlaxoSmithKline Vaccines, Bangalore, India

11 GlaxoSmithKline Vaccines, King of Prussia, PA, USA

12 GlaxoSmithKline Vaccines, Wavre, Belgium

13 CIC deVaccinologie Cochin Pasteur, Hopital Cochin, 27 Rue du Faubourg St.Jacques, 75679 Paris, France

For all author emails, please log on.

BMC Infectious Diseases 2013, 13:435  doi:10.1186/1471-2334-13-435

Published: 16 September 2013

Abstract

Background

Pandemic influenza vaccine manufacturing capacity and distribution agility is enhanced through the availability of equivalent antigen-sparing vaccines. We evaluated equivalence in terms of immunogenicity between GlaxoSmithKline Vaccines’ A/California/7/2009 (H1N1)v-like-AS03 vaccines manufactured in Dresden (D-Pan), and Quebec (Q-Pan).

Methods

In two studies, 334 adults 18-60 years of age received 2 doses of D-Pan or Q-Pan containing 3.75 μg haemagglutinin antigen (HA) adjuvanted with AS03A administered 21 days apart, and 209 children 3-9 years of age received 1 reduced dose of D-Panor Q-Pan (0.9 μg HA) or Q-Pan (1.9 μg HA) with AS03B. Haemagglutination inhibition (HI) titres were assessed before and 21 days post-vaccination. HI persistence was assessed after 12 months in adults and 6 months in children.

Results

Pre-defined criteria for immunological equivalence of Q-Pan versus D-Pan were achieved in both populations. After one vaccine dose, ≥97.6% of adults and children had HI titres ≥1:40, with increases in titre ≥25.7-fold. CHMP and CBER regulatory acceptance criteria for influenza vaccines were exceeded by all groups in both studies at Day 21. In adults,the percentage with HI titres ≥1:40 at Month 12 was 82.9% (Q-Pan) and 84.0% (D-Pan). In children, the percentages at Month 6 were 75.3.3% (Q-Pan0.9), 85.1% (D-Pan0.9) and 79.3% (Q-Pan1.9). Safety profile of the study vaccines was consistent with previously published data.

Conclusion

Two studies indicate that A/California/7/2009 (H1N1)v-like HA manufactured at two sites and combined with AS03 are equivalent in terms of immunogenicity in adults and children and highly immunogenic. Different HA doses elicited an adequate immune response through 180 days post-vaccination in children 3-9 years of age.

Trial registration

ClinicalTrials.gov: NCT00979407 and NCT01161160.

Keywords:
H1N1; Pandemic influenza vaccine; Influenza virus; Children; Adults; Persistence; Immunogenicity; Manufacturing capacity; Antigen dose reduction