Table on Clinical trials of pandemic and potentially pandemic influenza vaccines
Introduction
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Influenza vaccines are considered as among the most important and effective interventions for mitigating the effects of an influenza pandemic. However, uncertainty remains on the optimal choice of formulation for an effective vaccine, and needs to be evaluated in clinical trials. Current global production capacity for manufacturing of influenza vaccines is far from approaching what would be needed in order to protect the world's population, and considerable efforts are invested to increase the production capacity for influenza.
At present, manufacturers from several countries have reported to WHO their work to develop prototype pandemic influenza vaccines against H5 hemagglutinin subtype influenza A viruses. During 2009-2010, most producers became involved in clinical trials of candidate pandemic influenza A(H1N1) 2009 vaccines. Some manufacturers have also initiated development of vaccines against other avian viruses (such as H7 or H9 hemagglutinin subtype influenza A viruses). While most of the clinical trials have focused on healthy adults, new data is now available on safety and immunogenicity of vaccine candidates in the elderly and in children.
Results of clinical trials of H5 and H1 influenza vaccines reported to WHO at its meetings held in 2005-2011 indicate that these vaccines are safe and well tolerated in the age groups studied. Information on safety/reactogenicity is also available in publications or abstracts (See columns Reference of the Tables). Vaccine immunogenicity was demonstrated to vary based on type of vaccine, dose, and presence of adjuvants.
Clinical trials of aluminum adjuvanted split H5 vaccines showned modest increase in immunogenicity over unadjuvanted vaccines, but not sufficient to allow significant dose sparing. Evaluation of some split and subunit H5 vaccines formulated with proprietary adjuvants (such as MF59, AS and AF03) showed encouraging increase in immunogenicity. Some studies reveal that vaccination with currently available H5N1 prototype vaccines can also induce immune response against antigenically drifted H5N1 virus isolated at different times in a variety of geographical locations, similar to what is seen with seasonal influenza viruses.
Information on more than 80 clinical trials of pandemic H1N1 vaccines is included in the new version of the table. The immunogenicity of inactivated non-adjuvanted pandemic H1N1 vaccines proved unexpectedly good, as compared to what had been found with prototype H5N1 vaccines. Thus, most inactivated vaccines were able to elicit potentially protective antibody responses in adolescents, adults, elder adults and pregnant women within two – three weeks of administration of a single dose of vaccine. Vaccine effectiveness, however, was found to be substantially lower in HIV-infected persons, especially those with less than 200 CD4+ T-cells/µL. Poor immunogenicity results were similarly observed in organ transplant recipients, who are kept under immunosuppressive treatment.
In 2009-2010, several pandemic H1N1 vaccines were licensed and used for vaccination in many countries.
The table, compiled by WHO upon request of its Member States and of various stakeholders in the area of pandemic preparedness, provides an abbreviated description of data provided in preliminary form to WHO on the status of recent (last 7 years) development of vaccines directed against influenza strains with pandemic potential. The table is revised periodically. WHO also calls on those who have not participated in its previous consultations to make available information on planned on going vaccine trials for inclusion into the Table.
Because of inherent variability in the hemagglutination inhibition and neutralization antibody assay systems used to measure immunogenicity, and the lack of standardized methods for these assays, it is unwise to attempt to make direct comparisons of results from different clinical trials. Moreover, data presented was in some cases obtained in small groups of volunteers, and further trials will be needed.
This table was developed using data from:
- IFPMA, http://www.ifpma.org/Documents/NR5877/Table_Avian_Pandemic_Influenza_RnD_17Oct06.pdf
- International Clinical Trials Registry Platform (ICTRP), http://www.who.int/ictrp/en/
- ClinicalTrials.gov, http://clinicaltrials.gov/ct2/search
Other sources of the information include materials presented at technical meetings convened by WHO, publications and direct contacts with manufacturers and investigators in charge of clinical trials. Upon specific request of clinical investigators or manufacturers, some data has not been included in the table, as indicated by the mention (No data).
The current version of the Table is proposed as an Excel document. This allows users to filter (using a drop down menu) the data for the following variables:
- Type of vaccine
- Producer
- Subtype of influenza virus
- Strain of influenza virus
- Substrate for production
- Adjuvant used
- Dose
- Clinical development phase
- Number of subjects
- Age
- Schedule
- Route of administration of the vaccine
The Government of Canada is thanked for generous support to the initiation of this work.