Pandemic preparedness: lessons learnt from H2N2 and H9N2 candidate vaccines
N Hehme1, H Engelmann, W Künzel
1GlaxoSmithKline Biologicals, SSW Dresden, Zirkusstrasse 40, 01069 Dresden, Germany. norbert.w.hehme@gsk.com
Medical Microbiology and Immunology
|November 30, 2002
Summary
New influenza vaccine formulations using low-dose hemagglutinin (HA) with aluminum (Al) adjuvants and whole virus can increase pandemic vaccine supplies. Two doses of these experimental vaccines induced protective antibody levels, even with reduced antigen content.
Area of Science:
- Immunology
- Vaccinology
- Public Health
Background:
- Influenza pandemics pose a significant threat due to potential vaccine shortages.
- Current trivalent vaccines with 15 µg hemagglutinin (HA) per dose may not meet demand.
- Single doses of standard HA amounts are insufficient for unprimed individuals.
Purpose of the Study:
- To investigate modified influenza vaccine formulations for increased production yields.
- To assess the immunogenicity and safety of low-dose, whole-virus, Al-adjuvanted vaccines.
- To determine optimal dosing for protective antibody levels in various populations.
Main Methods:
- Dose-finding studies in healthy adults and elderly comparing experimental vaccines to a standard split virus vaccine (Fluarix).
- Evaluation of immune responses, including hemagglutination inhibition (HAI) titers.
- Feasibility trials to assess reactogenicity of Al-adjuvanted low-dose vaccines.
- Studies in unprimed populations using H2N2 and H9N2 candidate vaccines.
Main Results:
- Al-adjuvanted, low-dose (1.9 µg HA/strain) vaccines induced protective antibody levels in primed populations after one dose.
- Neither Al-adjuvant nor whole virus significantly affected general reactogenicity.
- Two doses of experimental vaccines were required to achieve protective HAI titers in unprimed populations.
- Up to eightfold reduced antigen content in Al-adjuvanted whole virus formulations was effective with two doses.
Conclusions:
- Al-adjuvanted whole virus vaccines with low HA content can elicit protective antibody levels with a two-dose regimen.
- This approach offers a strategy to significantly increase vaccine supplies during a pandemic.
- Further studies confirmed the need for two doses in unprimed individuals for protective immunity.
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