Adjuvanted trivalent influenza vaccine study in infants:
A randomised controlled trial to determine the kinetics of the functional genomic response
In the 2012 influenza season, ADITEC partners (Geneva, Oxford, Emory and Novartis) conducted a randomised controlled trial to assess the kinetics of the functional genomic response to adjuvanted trivalent influenza vaccine (TIV) in comparison with standard seasonal TIV and correlated with immunophenotypical data. Two doses of vaccine were administered one month apart. There were questions over the feasibility of using the systems immunology approach to vaccine assessment in young children (14-24 months in this trial) since only small volumes of blood (6mls) could be obtained for the study. Ninety children were enrolled and blood sampled at day 0, 1, 3 and 28 after the second dose of vaccine. To limit the number of blood samples per child, 2 groups were enrolled with an individual child allocated either to day 1 or day 3 sampling. Remarkably samples were obtained for gene expression studies (RNA), B and T cell EliSpots, flow cytometry and antibody measurement (using haemagglutination inhibition; HAI). Immunological analyses were undertaken in Oxford and HAI in Italy with microarray data analysed at Emory.
The majority of children were influenza naïve, since the previous season had a very low attack rate in the UK, and the majority were antibody and T cell response negative at baseline. Both vaccines were well tolerated. After vaccination, B cell, T cell, antibody and gene expression responses could be detected in the peripheral blood of the children and will be reported in a manuscript which is currently in preparation.
Comparison with previous adult studies of influenza vaccines indicate that there are striking differences in the response to immunisation in early childhood.
These findings warrant further investigation to direct new understanding of the developing immune system and require a study which is focussed on the timepoints identified in this first ADITEC TIV study in young children.
Rino Rappuoli awarded Fellowship by Imperial College Faculty of Medicine
ADITECs Project Coordinator Rino Rappuoli, Chief Scientist for GSK’s Vaccines business, gains prestigious recognition for his outstanding contribution to medical sciences.He has been awarded a Fellowship by Imperial College London’s Faculty of Medicine in recognition of his outstanding contribution to medical sciences.
“Rino’s passion for scientific development continues to impress us and is well-deserving of this recognition,” said Emmanuel Hanon, Head of R&D. “His work in vaccines and immunology extends beyond the walls of GSK, and we are thankful ofr the work he has done to make the world a healthier place.”
Rino was selected by the faculty not only for his career developing vaccines, but also for being jointly responsible for engineering the carier protein used in many conjugate vaccines. Several of the molecules he worked on became part of licensed vaccines against pandemic influenza, pertussis and meningitis.
WHO consultation on clinical evaluation of vaccines
In 2014, WHO held a consultation on guidelines for National Regulatory Authorities (NRAs) and vaccine manufacturers on clinical evaluation of vaccines. Aim was to review key scientific challenges that regulators have been facing since the establishment of the WHO Guidelines on Clinical Evaluation of Vaccines. The consultation concluded that the guidelines should be revised to address issues that were raised in the context of vaccines that were the subject of clinical development in the past decade. It was recognized that an update would further increase their utility and would help regulators, manufacturers, vaccine developers and academia to respond to the challenging questions regarding the safety, immunogenicity, efficacy and effectiveness of vaccines intended for global use. A summary of the main outcomes of the consultation and proposals for the next steps regarding the guidelines and beyond are provided in this report. ADITEC supported this process financially.
ADITEC present at Latvian Presidency meeting
On 12 May 2015 the Latvian Presidency of the Council of the European Union, organised the event: European Union contribution to infectious disease research, in Riga. Robin Shattock, member of the ADITEC Steering Committee, presented the ADITEC project: the power of immunization, the aim of the project, and how collaboration between the over 40 partners brings new sulotions. This presentation can be viewed as of 15.15 minutes from the start of this video.
ADITEC support for Innovative SME’s
The ADITEC project has launched three calls for the support of commissioned research by European Small and Medium size Enterprises (SME’s) and Public Health Organizations). Through these calls the ADITEC project provided the opportunity for SMEs and Public Health organizations to access advanced immunization technologies from consortium partners.
The first call was sent out in April 2013, and final recipients of the grants included Vaxil BioTherapeutics Ltd in Israel, for their project titled, “The protection properties of a novel multi-antigenic and multi-epitopes subunit vaccine with pan-HLA coverage against M. tuberculosis”, Cilian AG in Germany for, “Design of an influenza vaccine candidate based on recombinant subunit vaccine produced in ciliates and biodegradable particles as vaccine carrier” and lastly, Sigmoid Pharma Ltd. in Ireland for their project titled, “Targeted large intestinal release of chlamydia vaccine antigens to promote genital tract immunity”. ADITEC was recognized by these SMEs as an opportunity to access advanced technologies, but also for the opportunity to develop close interactions and receive expert advice and consultation from colleagues in leading institutions in the vaccine field. The results of project from the first call are becoming available. Read the summary results of Vaxil BioTherapeutics.
Two proposals for third round commissioned research awarded
In December 2014 ADITEC launched the third call for commissioned research support for SMEs and PHO’s (see also above message). The ADITEC steering committee received two proposals on this call, from Bioneedle Technologies Group (SME in The Netherlands) and the Public Health Department of the Federal State of Tyrol, Innsbruck, Austria. Both proposals were reviewed and the Steering Committee decided in May to approve both proposals:
- The Public Health Department of the Federal State of Tyrol submitted the project: ‘Pneumococcal conjugate vaccines in the elderly: The role of carrier-specific T cells’.
- Bioneedle Technologies Group: Clinical Trial support.
3rd ADITEC training course on adjuvants and vaccine formulation completed
The World Health Organization (WHO) has established advanced training courses on vaccine adjuvants and formulation, taking place at the Vaccine Formulation Laboratory (VFL) at University of Lausanne (UNIL), Switzerland (a WHO Collaborating Centre in Immunology and Adjuvants). Following completion of the first two courses in September 2013, this was the 3rd course sponsored by the European Commission through the ADITEC project. Overall, eight participants attended the five-day practical course from 9-13 February 2015 at the VFL laboratories.
All participants were selected through a competitive process. Six of them, working within the EU, were funded by ADITEC, whereas two additional participants from outside of Europe (Sudan and Indonesia) were supported by WHO. Read more on our website.
Fellowships adjuvant formulation class
In January we announced a new training on adjuvants and vaccine formulation, to be held at the Vaccine Formulation Laboratory at University of Lausanne, Switzerland. We are happy to announce that the following fellows are being supported by ADITEC for this training:
- Batejat, InnaVirVax
- Berthels, Federal Agency of Medicines and Health Products
- Fiorino, University of Siena – Dept Medical Biotechnologies
- Rollier, University of Oxford
- Dobadei, Novartis Vaccines and Diagnostics
- Reis, AC Immune SA
- Longet, Trinity College Dublin, Adjuvant Research Group
- Lammerink, Bilthoven Biologicals B.V
- Sirard, Institut Pasteur de Lille
- Clausi, Karolinska Institutet
- Oliveira Cavalcanti, Boehringer Ingelheim Veterinary Research Center
In addition, WHO will sponsor the following participants:
- Luenchaichawange, BioNet-Asia Co., Ltd.
- Patarakul, Department of Microbiology, Faculty of Medicine, Chulalongkorn University
€1M EC prize for better use of antibiotics
The European Commission introduced a ‘Horizon Prize for better use of antibiotics’. This €1 million prize addresses the issue of the unnecessary use of antibiotics, which is contributing to the growing problem of antibiotic resistance. The challenge is to develop a rapid test that will allow healthcare providers to distinguish at the point of care between patients with upper respiratory tract infections that require antibiotics and those that can be treated safely without antibiotics. More information can be found on the website of the European Commission.
Free EURIPRED services
EURIPRED is an infrastructure project, funded by the European Commission, to facilitate and support translational research for poverty related diseases, such as HIV, TB, malaria and hepatitis. The services provided by EURIRPED can be accessed for FREE by European scientists. On a regular basis, calls will be sent out so interested participants can apply.
The EURIPRED services are:
- Biological materials and reference reagents/ standards
- Vaccine adjuvant & formulation
- Microarray facility for screening & evaluation
Application for free services will be selected under a peer-reviewed process. Only European user groups (from EU Member States or Associated States) can apply for the free services, and only to EURIPRED Services outside their own country. For scientists based in countries outside the EU Member States or its Associated States, access is subject to a range of charges according to the service requested.
Infrastructure for Systems Biology Europe
The Infrastructure for Systems Biology Europe (ISBE) is a European research infrastructure that empowers scientists to understand how living organisms function to a level that allows rational and effective intervention in how biological systems operate. Systems biology uses computer models which integrate diverse experimental data sets. These mathematical models are vital tools for understanding how biological systems function, to a level that allows predicting how they respond to internal and external changes. This allows life science researchers to deliver solutions that address societal grand challenges in health and quality of life, bio-economy and sustainability.
By interconnecting national systems biology centres and making their collective expertise, resources and services easily accessible for all European researchers, ISBE will bring systems biology within easy reach of scientists.
Through ISBE, researchers will be able to gain easy access to the best systems biology expertise, resources and services including state-of-the-art facilities, data, models, tools and training.
ISBE will drive the development and uptake of standards for biological data, tools and models as well as operating procedures, ensuring that data and models across different laboratories, countries and sectors become combinable and re-usable.
SYSBIO – Centre of Systems Biology is the Italian institute for Systems Biology, and ISBE Associate partner.
Within and outside the ADITEC network several interesting meetings will take place in the coming months. For example
- 14-07-15 – 18-07-15 | ICMI 2015
- 21-07-15 – 22-05-15 | International Conference on Innate Immunity
- 17-08-15 – 19-08-15 | 6th Euro Global Summit and Expo on Vaccines and Vaccination
- 24-08-15 – 26-08-15 | International Symposia on “Control of avian influenza and preparedness for pandemic influenza”
- 06-09-15 – 09-09-15 | 4th European Congress of Immunology
- 25-09-15 – 26-09-15 | ICI 2015: 17th International Conference on Immunology
- 28-09-15 – 30-09-15 | 4th International Conference and Exhibition on Immunology
- 10-01-16 – 14-01-16 | Keystone symposium: Systems Immunology: From Molecular Networks to Human Biology
- More interesting meetings in the field of immunology can be found here
This is the list with recent publications related to the ADITEC project:
- Dysregulation of Apoptosis Is a Risk Factor for Tuberculosis Disease Progression
Thomas O. J. P. Elliott1, Olumuyiwa Owolabi, Simon Donkor, Beate Kampmann, Philip C. Hill, Tom H. M. Ottenhoff, Marielle C. Haks, Stefan H. E. Kaufmann, Jeroen Maertzdorf and Jayne S. Sutherland
J Infect Dis. (2015) doi: 10.1093/infdis/jiv238
- Differential transcriptomic and metabolic profiles of M. africanum- and M. tuberculosis-infected patients after, but not before, drug treatment.
Tientcheu LD, Maertzdorf J, Weiner J, Adetifa IM, Mollenkopf HJ, Sutherland JS, Donkor S, Kampmann B, Kaufmann SH, Dockrell HM, Ota MO.
Genes Immun. 2015 Jun 4. doi: 10.1038/gene.2015.21. [Epub ahead of print]
- Molecular signatures for vaccine development.
Maertzdorf J, Kaufmann SH, Weiner J.
Vaccine. 2015 Apr 6. pii: S0264-410X(15)00394-1. doi: 10.1016/j.vaccine.2015.03.075. [Epub ahead of print]
- WHO consultation on clinical evaluation of vaccines, 17-18 July 2014, WHO Headquarters, Geneva, Switzerland.
Knezevic I, Moorthy V, Sheets R.
Vaccine. 2015 Apr 21;33(17):1999-2003. doi: 10.1016/j.vaccine.2015.01.056. Epub 2015 Mar 4.
- Protein Energy Malnutrition during Vaccination Has Limited Influence on Vaccine Efficacy but Abolishes Immunity if Administered during Mycobacterium tuberculosis Infection.
Truc Hoang, Else Marie Agger, Joseph P Cassidy, Jan P Christensen, Peter Andersen
Infect Immun 2015 May 9;83(5):2118-26. Epub 2015 Mar 9.
- Protection Against Chlamydia trachomatis Infection and Upper Genital Tract Pathological Changes by Vaccine-Promoted Neutralizing Antibodies Directed to the VD4 of the Major Outer Membrane Protein.
Olsen AW, Follmann F, Erneholm K, Rosenkrands I, Andersen P.
J Infect Dis. 2015 Mar 6. pii: jiv137. [Epub ahead of print]
- Rapid development of broadly influenza neutralizing antibodies through redundant mutations.
Pappas L, Foglierini M, Piccoli L, Kallewaard NL, Turrini F, Silacci C, Fernandez-Rodriguez B, Agatic G, Giacchetto-Sasselli I, Pellicciotta G, Sallusto F, Zhu Q, Vicenzi E, Corti D, Lanzavecchia A.
Nature. 2014 Dec 18;516(7531):418-22. doi: 10.1038/nature13764. Epub 2014 Oct 5.
- Clinical Immunology and Multiplex Biomarkers of Human Tuberculosis.
Walzl G, Haks MC, Joosten SA, Kleynhans L, Ronacher K, Ottenhoff TH.
Cold Spring Harb Perspect Med. 2014 Dec 4;5(4). pii: a018515. doi: 10.1101/cshperspect.a018515.
- The effect of hyperglycaemia on in vitro cytokine production and macrophage infection with Mycobacterium tuberculosis.
Lachmandas E, Vrieling F, Wilson LG, Joosten SA, Netea MG, Ottenhoff TH, van Crevel R.
PLoS One. 2015 Feb 9;10(2):e0117941. doi: 10.1371/journal.pone.0117941. eCollection 2015.
- Acquired immunodeficiencies and tuberculosis: focus on HIV/AIDS and diabetes mellitus.
Ronacher K, Joosten SA, van Crevel R, Dockrell HM, Walzl G, Ottenhoff TH.
Immunol Rev. 2015 Mar;264(1):121-37. doi: 10.1111/imr.12257.
- The Recombinant BCG ΔureC::hly Vaccine Targets the AIM2 Inflammasome to Induce Autophagy and Inflammation.
Saiga H, Nieuwenhuizen N, Gengenbacher M, Koehler A, Schuerer S, Moura-Alves P, Wagner I, Mollenkopf H, Dorhoi A, Kaufmann SH.
J Infect Dis. 2014 Dec 11. pii: jiu675. [Epub ahead of print]
- The human immune response to tuberculosis and its treatment: a view from the blood.
Cliff JM, Kaufmann SH, McShane H, van Helden P, O’Garra A.
Immunol Rev. 2015 Mar;264(1):88-102. doi: 10.1111/imr.12269.
- Biomarkers Can Identify Pulmonary Tuberculosis in HIV-infected Drug Users Months Prior to Clinical Diagnosis
Rosa Sloot, Maarten F. Schim van der Loeff, Erik W. van Zwet, Mariëlle C. Haks, Sytze T. Keizer, Maarten Scholing, Tom H.M. Ottenhoff, Martien W. Borgdorff, Simone A. Joosten,
EBioMedicine, Volume 2, Issue 2, February 2015, Pages 107-108
- Using Plasmids as DNA Vaccines for Infectious Diseases
John S. Tregoning, Ekaterina Kinnear
Microbiolspec November 2014 vol. 2 no. 6 doi:10.1128/microbiolspec.PLAS-0028-2014