Tech­nical article of the WHO on microneedle patches

Applic­a­bility of microarray patches to vac­cine delivery in low and middle income countries

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There is an urgent need for new tools and approaches to reach the 20 mil­lion infants that are not fully immu­nized each year.1 The majority of the 1.5 mil­lion deaths that result from vac­cine pre­ventable dis­eases occur in just a handful of coun­tries, with the weakest health­care infra­struc­ture, and where it is an enor­mous chal­lenge to reach remote or con­flict areas. Vac­cine delivery in these coun­tries is ham­pered by the require­ment for most vac­cines to be refrig­er­ated from the point of pro­duc­tion to the point of admin­is­tra­tion, the need to cor­rectly pre­pare the vac­cine by a trained health­care worker, and the fact that many care­givers and chil­dren don’t like nee­dles or the pain asso­ci­ated with them.2

Most vac­cines are man­u­fac­tured as multi-dose vials to reduce cost, but this pre­sen­ta­tion means there is reluc­tance to open the vac­cine if there are not mul­tiple chil­dren at the facility at the moment of vac­ci­na­tion. Microarray patches (MAPs) are designed to address these issues and rev­o­lu­tionise vac­cine delivery in low and middle income countries.

MAPs con­sist of a cluster of thou­sands of micronee­dles less than 1mm long attached to a backing, which can be applied to the skin with finger pres­sure or an appli­cator. The micronee­dles reach the dermis or epi­dermis to dif­fuse or dis­solve the vac­cine to immune cells that evoke a strong immune response. MAPs offer sig­nif­i­cant advan­tages over the existing vac­cine pre­sen­ta­tions.3

Can be kept out­side the cold chain

They are designed to deliver a single dose without any vac­cine prepa­ra­tion and are easy to apply. They can poten­tially be kept out­side the cold chain, facil­i­tating the delivery by min­i­mally trained per­sonnel in hard to reach and remote places.4 As MAPs target the vac­cine directly to immune cells, they could allow for a reduc­tion in the vac­cine dose as com­pared to con­ven­tional delivery of vac­cines, which can reduce both cost and increase the number of avail­able doses during vac­cine short­ages.5,6

MAPs are in product devel­op­ment for influenza7–9, Hepatitis B10,11 (HepB), Human Papil­lo­mavirus12 (HPV), Measles-Rubella13 (MR) and other vac­cines. The first dose of HepB vac­cine is rec­om­mended to be given at birth, and vac­ci­na­tion often takes place out­side of a health­care facility by min­i­mally trained per­sonnel.14 A MAP HepB ther­mostable vac­cine that is easy to trans­port and deliver could incre­men­tally increase the pro­por­tion of vac­ci­nated infants with HepB at birth.10

Com­bating Hepatitis B and Measles-Rubella

The MR vac­cine is a multi-dose vial with strin­gent tem­per­a­ture require­ments that needs to be used within six hours from opening. A MAP-MR vac­cine that is ther­mostable, easy to deliver and single dose would facil­i­tate delivery of vac­cines in out­breaks and during immu­ni­sa­tion cam­paigns.13 Delivery of HepB and MR by MAPs are con­sid­ered as poten­tial game-changers for the elim­i­na­tion agendas of these vaccines.

There is a clear public health imper­a­tive to develop the MAPs delivery plat­form for vac­cines. The imple­men­ta­tion of this delivery strategy could sig­nif­i­cantly increase the pro­por­tion of vac­ci­nated chil­dren in the world’s most impov­er­ished areas and save lives.


1. UNICEF. WUENIC Ana­lytics. (2019).
2. Arya, J. & Praus­nitz, M. R. Microneedle patches for vac­ci­na­tion in devel­oping coun­tries. J.Control Release (2016).doi:10.1016/j.jconrel.2015.11.019.
3. Suh, H., Shin, J. & Kim, Y.-C. Microneedle patches for vac­cine delivery. Clin. Exp. Vac­cine Res. (2014). doi:10.7774/cevr.2014.3.1.42.
4. Giersing, B. K. et al. Chal­lenges of vac­cine pre­sen­ta­tion and delivery: How can we design vac­cines to have optimal pro­gram­matic impact? Vac­cine (2017). doi:10.1016/j.vaccine.2017.04.063.
5. Praus­nitz, M. R. Engi­neering Microneedle Patches for Vac­ci­na­tion and Drug Delivery to Skin. Annu. Rev. Chem. Biomol. Eng. (2017). doi:10.1146/annurev-chembioeng-060816–101514.
6. Chan­drasekhar, S. et al. Microar­rays and microneedle arrays for delivery of pep­tides, pro­teins, vac­cines and other appli­ca­tions. Expert Opin. Drug Deliv. (2013). doi:10.1517/17425247.2013.797405.
7. Rouphael, N. G. et al. The safety, immuno­genicity, and accept­ability of inac­ti­vated influenza vac­cine deliv­ered by microneedle patch (TIV-MNP 2015): a ran­domised, partly blinded, placebo-con­trolled, phase 1 trial. Lancet (2017). doi:10.1016/S0140-6736(17)30575–5.
8. Fer­nando, G. J. P. et al. Safety, tol­er­a­bility, accept­ability and immuno­genicity of an influenza vac­cine deliv­ered to human skin by a novel high-den­sity micro­pro­jec­tion array patch (NanopatchTM). Vac­cine (2018). doi:10.1016/j.vaccine.2018.05.053.
9. Hirobe, S. et al. Clin­ical study and sta­bility assess­ment of a novel tran­scu­ta­neous influenza vac­ci­na­tion using a dis­solving microneedle patch. Bio­ma­te­rials (2015). doi:10.1016/j.biomaterials.2015.04.007.
10. Poirier, D. et al. Hepatitis B sur­face antigen incor­po­rated in dis­solv­able microneedle array patch is anti­genic and ther­mostable. Bio­ma­te­rials (2017). doi:10.1016/j.biomaterials.2017.08.038.
11. Qiu, Y. et al. DNA-based vac­ci­na­tion against hepatitis B virus using dis­solving microneedle arrays adju­vanted by cationic lipo­somes and CpG ODN. Drug Deliv. (2016). doi:10.3109/10717544.2014.992497.
12. Cor­bett, H. J., Fer­nando, G. J. P., Chen, X., Frazer, I. H. & Kendall, M. A. F. Skin vac­ci­na­tion against cer­vical cancer asso­ci­ated human papil­lo­mavirus with a novel micro-pro­jec­tion array in a mouse model. PLoS One (2010). doi:10.1371/journal.pone.0013460.
13. Joyce, J. C. et al. A Microneedle Patch for Measles and Rubella Vac­ci­na­tion Is Immuno­genic and Pro­tec­tive in Infant Rhesus Macaques. in Journal of Infec­tious Dis­eases (2018). doi:10.1093/infdis/jiy139.
14. World Health Orga­ni­za­tion (WHO). Hepatitis B vac­cines: WHO posi­tion paper – July 2017. World Heal. Organ. Geneva (2016). doi:10.1186/1750–9378‑2–15.

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Authors: Mateusz Hasso-Agop­sowicz, Project Man­ager, Ini­tia­tive for Vac­cine Research, WHO, Geneva, Switzer­land und Bir­gitte Giersing, Tech­nical Officer, Ini­tia­tive for Vac­cine Research, WHO, Geneva, Switzerland 

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