Stretching the flu vaccine?

In this flu-vaccine shortage year, any means of extending the vaccine supply is worth examining. There is evidence that giving vaccines intradermally rather than intramuscularly is more effective. In last week’s NEJM are two articles examining the effect of administering a lower dose of the flu vaccine intradermally. There is also a letter to the editor looking at the effect of simply giving a lower dose of the vaccine by the traditional i.m. route.

In the first study, sponsored by Glaxo SmithKline, 238 subjects were randomized to either a standard 0.5 ml i.m. dose of flu vaccine or a 0.1 ml intradermal dose of a candidate vaccine that was double concentrated (yielding an intradermal vaccine with 40% the concentration of antigen of the standard vaccine). 130 subjects were aged 18-60 years, 108 were over 60 years of age (average age: 69). In the younger group, the antibody responses were almost the same and were adequately protective in the intradermal group. In the group of subjects over 60 years old, the intradermal route yielded antibody titers that were generally lower, significantly lower for one strain and probably only incompletely protective.

In the second study, suppored by NIH grants, 100 subjects 18-40 years of age were randomized to receive either a standard 0.5 ml i.m. dose of a standard flu vaccine, or 0.1 ml of the same vaccine given intradermally. The intradermal route yielded, overall, a similar (for some strains better) antibody response as the i.m. route.

In the letter to the editor, a group from Canada gave healthy volunteers aged 18-40 years old either a full dose or a 1/10 dose of an influenza vaccine by the intramuscular route. Those given the 1/10 dose achieved protective antibody levels (although lower titers for most strains).

These studies indicate that the intradermal route produces better immunogenicity than the i.m. route. This could be used to enhance the immune response in populations that mount a less effective response (such as the elderly). It could also be used to stretch the vaccine supply in case of future shortages, particularly in the younger population. The practical effectiveness of these approaches will depend, at least in part, on FDA approval of different dosages and routes. It seems unlikely that a manufacturer of a conventional influenza vaccine will apply for approval of one-fifth of the dose of that same vaccine, administered intradermally. The Glaxo SmithKline approach of manufacturing a different product is more likely to be financially attractive.

One thought on “Stretching the flu vaccine?

  1. mjmd

    [Author’s comments]

    Dr. Robert Belshe, corresponding author for this article, has emailed me two comments about my summary:

    Concerning the second paragraph, where I stated: “In the younger group, the antibody responses were almost the same and were adequately protective in the intradermal group”:

    We don’t know that the ID vaccine was protective or not protective and this was not claimed in the article. We only know its relative immunogenicity vs the full dose IM.

    Concerning the last paragraph:

    These studies indicate that the ID route is promising for use of lower doses. We do not know whether lower doses given IM would work just as well and this needs to be studied. We did not claim that ID was better but it might be.

    I very much appreciate these clarifications.

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