Influenza Vaccination

Abstract

Influenza viruses have traditionally been administered by intramuscular injection. The invention is based on the idea of using alternative routes of delivery for influenza vaccines, more specifically routes that do not require as large a dose of antigen. Delivery of influenza antigen to the Langerhans cells is the route of choice according to the invention. This route has been found to be particularly useful for vaccinating patients who are naive to influenza virus (i.e. have not previously mounted an immune response to an influenza virus), which means that it is advantageous for immunising young children.

Description

FIELD OF THE INVENTION[0001]This invention concerns influenza virus vaccines, and in particular pediatric vaccines for delivery to the Langerhans cells.BACKGROUND OF THE INVENTION[0002]In the past, influenza vaccines have generally been administered to patients at particular risk from the consequences of influenza infection, such as: children with asthma, cardiac disease, sickle cell disease, HIV or diabetes; children living in a household containing someone suffering from asthma, cardiac disease, sickle cell disease, HIV or diabetes; and the elderly.[0003]More recently, there have been suggestions that the scope of influenza vaccination should be extended to include all children, rather than just those at high risk. To increase coverage in this way, however, would require a huge increase in production capacity, and vaccine manufacturers are not well placed to deliver this increase. Stockpiling of vaccines is not possible because the vaccine strains change every year and are produce...

AI Technical Summary

Benefits of technology

[0006]As well as increasing the number of vaccine doses that can be produced from a given amount of antigen, a move away from intramuscular injection means that the invention avoids the pain associated with influenza vaccination, thereby increasing both patient comfort and compliance.

[0030]Langerhans cells are highly specialised myeloid antigen-presenting cells (APCs) located in the skin, mucosa, and lymphoid tissues. The Langerhans cells originate in the bone marrow and migrate to the epidermis, where they form a regularly ordered network that can reach a density of 700 to 800 cells per mm2, covering up to 25% of total skin surface area in humans. The cells are easily recognised in electron microscope images as they contain characteristic intracellular cytoplasmic organelles resembling tennis rackets, known as the “Langerhans-granula” or “Birbeck granules”. Langerhans cells are rich in Class II MHC. They can specifically activate dormant T-helper cells and thus initiate a primary T-cell dependent immune response. After contact with an antigen the cell can leave the epidermis and reach a lymph node via the lymphatic system. On its journey the cell will undergoes a maturation process leading to the presentation of the antigen on the cell surface. The migrating cells are replaced by a corresponding number of new Langerhans cells from the bone marrow. In the lymph nodes the mature Langerhans' cells activate the T-helper cells that have the matching antigen-specific receptors on their surfaces. In this way they steer the reaction of the immune system.

[0033]Delivery can be achieved using devices that create micropores in the stratum corneum (“microporation”). Such devices include microstructures (sometimes called microneedles, which is now an accepted term in the art [37-40]) that, when applied to the skin, painlessly create micropores in the stratum corneum without causing bleeding (e.g. 3M's Microstructured Transdermal System, the Micropyramid™ system from NanoPass, etc.). The microneedles can be used singly or in a plurality (e.g. in an array [41]). The microneedles open pores in the stratum corneum and can take various sizes e.g. ranging in length from 25 μm to 1 mm. They are preferably small enough not to penetrate into the dermis and so not to reach the nerve endings, thereby avoiding any sensation of pain. The structures can be either solid (serving as a pretreatment prior to antigen application), solid with antigen coated directly on the outside of the needles, or hollow to facilitate fluidic transport through the needles and into the lower epidermis. They can be made from materials including, but not limited to: silicon, biodegradable polymers, metals (e.g. stainless steel, gold, etc.), and glass. Biodegradable polymers are safe even if needles snap off while inserted. The micropores produced by these devices offer lower resistance to drug diffusion than normal skin without micropores [42], and the systems have been reported to greatly enhance (up to 100,000 fold) the permeation of macromolecules through skin [43]. Vibratory actuation can be used in order to reduce the insertion force [44].

[0037]Iontophoresis and sonophoresis can be used to increase flux across the stratum corneum. These systems can achieve significant skin permeation enhancement, including for proteins [47,48], particularly in the absence of hair.

Problems solved by technology

To increase coverage in this way, however, would require a huge increase in production capacity, and vaccine manufacturers are not well placed to deliver this increase.

Stockpiling of vaccines is not possible because the vaccine strains change every year and are produced almost in a just-in-time manner.