Combination vaccines with low dose of hib conjugate

Abstract

Provided herein are combination vaccines comprising antigens for protecting a subject against at least diphtheria, tetanus, pertussis and Hib, wherein: (a) the antigen for protecting against Hib is a conjugate of a Hib capsular saccharide; (b) the concentration of the Hib conjugate in the vaccine is <15 μg / ml; and (c) the Hib conjugate has never been lyophilised.

Description

[0001]All documents cited herein are incorporated by reference in their entirety.TECHNICAL FIELD[0002]This invention is in the field of combination vaccines, particularly those for protecting against diphtheria, tetanus, pertussis and H. influenzae type b (‘Hib’).BACKGROUND ART[0003]Combination vaccines including antigens for immunizing against diphtheria, tetanus, pertussis and Hib are known (‘DTP-Hib’ vaccines). Three such vaccines have been marketed under the names TETRAMUNE™ and QUATTVAXEM™ (which use cellular pertussis antigens ‘DTwP-Hib’) and INFANRIX-Hib™ (which uses acellular pertussis antigens ‘DTaP-Hib’).[0004]The inclusion of Hib-conjugate components in DTaP-Hib vaccines has been associated with reductions in the anti-Hib response [1, 2]. Furthermore, Hib-conjugates are unstable in aqueous media and cannot survive prolonged storage in this form [3]. For this reason, in combination vaccines that include Hib-conjugate antigens, it is common for the Hib component to be provi...

AI Technical Summary

Benefits of technology

The invention provides a combination vaccine that protects against diphtheria, tetanus, pertussis, and H. influenzae type b (Hib). The vaccine contains a conjugate of a Hib capsular saccharide as the antigen for protecting against Hib. The concentration of the Hib conjugate in the vaccine is less than 15 μg / ml. The vaccine is safe and immunogenic. The invention also provides a process for preparing the combination vaccine and a process for inserting the vaccine into a container. The technical effects of the invention are improved safety and immunogenicity of the combination vaccine compared to separate vaccines, as well as simplified preparation and packaging of the vaccine.

Problems solved by technology

Furthermore, Hib-conjugates are unstable in aqueous media and cannot survive prolonged storage in this form [3].

Hib-conjugate antigens are not cheap to produce, and there is concern that their cost will inhibit widespread use in developing countries, and so alternative strategies for Hib-conjugate use have been developed [4-6].

These vaccines must thus be provided in two separate containers (aqueous DTP in one, lyophilised Hib in the other), and this double container requirement imposes additional cost and logistical requirements at the packaging stage, the transport stage, the storage stage and the administration stage.

As the reduced-dose vaccines are intended to reduce cost and encourage distribution in the developing world then these additional requirements are significant disadvantages.

The requirement for a reconstitution step also means that there is a risk of error by the end user, a tendency towards non-standardised dosages, a risk of contamination of the mixed product and a need to train staff in the reconstitution procedure.

All of these problems frustrate the intended target market i.e. the developing world.

Images