1: Immunology. 2007 May 22; [Epub ahead of print]

The delivery site of a monovalent influenza vaccine within the respiratory tract
impacts on the immune response.

Minne A, Louahed J, Mehauden S, Baras B, Renauld JC, Vanbever R.

Department of Pharmaceutical Technology, Université catholique de Louvain,
Brussels, Belgium.

Pulmonary vaccination is a promising immunization route. However, there still
remains a crucial need to characterize the different parameters affecting the
efficacy of inhaled vaccination. This study aimed at assessing the impact of
antigen distribution within the respiratory tract on the immune response to a
monovalent A/Panama/2007/99 H3N2 influenza split virus vaccine administered to
BALB/c mice. Varying the administration technique allowed the targeting of the
vaccine to different sites of the mouse respiratory tract, i.e. the nasal cavity,
the upper or central airways, or the deep lung. This targeting was verified by
using ovalbumin as a tracer compound. The immune responses generated following
influenza vaccine administration to the different respiratory tract sites were
compared to each other and to those elicited by intramuscular and peroral
intragastric immunization. Delivery of the vaccine to the different respiratory
regions generated systemic, local and cellular virus-specific immune responses,
which increased with the depth of vaccine deposition, culminating in deep-lung
vaccination. The latter induced virus-specific serum immunoglobulin G and
neutralizing antibody titres as elevated as intramuscular vaccination, whereas
the production of mucosal secretory immunoglobulin A was significantly superior
in deep-lung-vaccinated animals. The analysis of cytokines secreted by
mononuclear cells during an in vitro recall response indicated that deep-lung
vaccination induced a local shift of the cellular immune response towards a T
helper type 1 phenotype as compared to intramuscular vaccination. In conclusion,
antigen distribution within the respiratory tract has a major effect on the
immune response, with the deep lung as the best target for inhaled influenza
vaccination.

PMID: 17521369 [PubMed - as supplied by publisher]

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