Where do alternative vaccine administration routes fit in the clinical landscape?

The Intramuscular and subcutaneous routes are the traditional methods for vaccine delivery. Prof. Marien de Jonge (Radboud University Medical Center, The Netherlands) reviewed current data on vaccines administered via alternative routes [1].

The intradermal route is attractive due to the high density of antigen-presenting cells present in the dermis, resulting in a potential dose-sparing effect. Currently, 3 vaccines have licensed intradermal administration: BCG, rabies, and influenza. Microneedles are 1 approach to intradermal delivery, enabling slow antigen release and mimicking natural pathogen exposure [1]. This strategy has been tested in preclinical models with a slow-release, alum-containing HIV vaccine [2]. Moving closer to clinical practice, a microneedle patch vaccine for measles and rubella achieved nearly 100% seroconversion with only mild adverse events in a phase 1/2 study in children <18 months of age [3].

The mucosal route offers the advantage of stimulating large populations of resident memory T cells and tissue-resident B cells. However, only a single intranasal influenza vaccine is currently licensed [1]. One promising candidate, BPZE, is an intranasal live-attenuated pertussis vaccine evaluated in a phase 2b trial in healthy adults, where it induced nasal mucosal immunity and functional serum responses [4]. Intranasal COVID-19 vaccines are also in development, but most remain in phase 1 [1,5].

“Intradermal and intranasal routes of administration offer significant potential and are gaining new relevance,” concluded Prof. de Jonge. “However, their adoption is limited by route-specific vaccine formulations and delivery mechanisms. This created the additional to develop novel correlates of protection”, he added [1].

1. De Jonge M. New developments in vaccination administration routes (intradermal, inhalation, mucosal). 6^th ESCMID Vaccines, 10–13 September 2025, Lisbon, Portugal.
2. Rodrigues KA, et al. Sci Transl Med. 2025;17(803):eadw7499.
3. Ikechukwu Adigweme, et al. Lancet. 2024;403(10439):1879-1892.
4. Keech C, et al. Lancet. 2023;401(10379):843-855.
5. Singh C, et al. NPJ Vaccines. 2023;8(1):125.

Medical writing support was provided by Mihai Surducan, PhD.

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Posted on 18 September 202521 October 2025