Laboratory methods for assessing vaccine potency retained in aerosol outputs from nebulizers: Application to World Health Organization measles aerosol project

doi:10.1016/j.vaccine.2008.04.027

Vaccine

Volume 26, Issues 27–28, 25 June 2008, Pages 3534-3539

https://doi.org/10.1016/j.vaccine.2008.04.027 Get rights and content

Abstract

Background

Laboratory methods for measuring vaccine potency of nebulized aerosol are required to support clinical trials of measles aerosol vaccination.

Methods

Measles vaccine containing the Edmonston Zagreb virus strain was reconstituted in sodium fluoride as tracer and nebulized from three devices. Emitted aerosol was collected using an impinger. Aliquots were removed from the impinger chamber for vaccine virus plaque assay and for fluoride measurement to determine aerosol output.

Results

Vaccine potency retention results were adjusted to take into account the effect of aerosol output on estimates. Adjusted potency of nebulized vaccine ranged from 88% to 102%.

Conclusions

New laboratory methods to measure aerosol vaccine potency retention were reliable and accurate. The results demonstrated that Edmonston Zagreb vaccine remains robust during aerosolisation and imply that this is a viable candidate for further evaluation in the measles aerosol project.

Introduction

World Health Organization (WHO) recently announced significant progress towards the goal of measles mortality reduction [1] yet in 2005 there were still more than 340,000 deaths per year due to measles globally, mainly in infants and children in developing countries in Asia and Africa [1]. WHO is therefore committed to assessing further enhancements of the measles control programme, including improved methods of vaccine delivery. Aerosol administration of measles vaccine is a promising non-invasive alternative to sub-cutaneous injection [2] and has recently been reviewed [3]. Some vaccine strains of measles virus appear to be less efficacious than others when administered as aerosol; in particular, there was evidence from a study in South Africa that the potency of the Schwarz vaccine strain was not retained when delivered as aerosol [4]. The Edmonston Zagreb strain, however, retained potency when aerosolized and in this form elicited sero-responses that were superior to those after corresponding sub-cutaneous injection [4], [5], [6]. Assessment of vaccine potency retention, or, the potency retained when vaccine is administered as aerosol, is therefore an important complementary activity required in support of current WHO clinical trials [3]. In this paper, we describe the development and standardisation of laboratory methods for measuring potency of measles vaccine administered as aerosol.

Section snippets

Study design

Three nebulizers, selected for use in WHO clinical trials, were used in the laboratory to validate methodology for measuring vaccine potency retention. Each nebulizer was operated three times in succession, for 30 s each time, and aerosol outputs were collected as described in Section 2.6. The operation time of 30 s was chosen to simulate the standard dosing regimen used in clinical trials. During the interval of about 30 min between operations nebulizers containing reconstituted vaccine were

Toxicity of fluoride marker

In a preliminary experiment the toxicity of the fluoride marker was investigated by re-constituting vaccine in ten-fold dilutions of sodium fluoride solution ranging from 0.00025% to 2.5% and measuring vaccine potency by plaque assay. Reconstitution in sterile water for injection was performed as a control. For this experiment, the manufacturer's recommended reconstitution volume of 5 mL was used. The results showed that the fluoride marker was not toxic for vaccine virus nor Vero cell cultures

Discussion

This work was performed with the support of WHO in order to determine losses in vaccine potency due to the nebulization process in general and, more specifically, to investigate whether different nebulizers being considered for use in the WHO Measles Aerosol Project (MAP) had different levels of vaccine potency retention. Given the lack of standardised research methods, we sought to develop and standardise methods to determine vaccine potency retention to meet the needs of the WHO project. The

Acknowledgements

The authors alone are responsible for the views expressed in this manuscript and they do not necessarily represent the decisions, policy or views of the World Health Organization. World Health Organization Initiative for Vaccine Research (WHO/IVR) co-ordinates the Measles Aerosol Project (MAP). The Centre for Disease Control and Prevention (CDC), USA and, the American Red Cross (ARC) are partners in MAP, which has received financial support from the Bill and Melinda Gates Foundation. We thank

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