Dissolvable microneedle patches are an effective and patient-preferred alternative to conventional hypodermic needles for administering the influenza vaccine, data from the first phase 1 human trial shows.
In addition, the patch, which consists of micron-scale, vaccine-filled needles embedded in a soft polymer base, can be stored and distributed without refrigeration and can be safely self-administered by patients, Nadine G. Rouphael, MD, associate professor of medicine in the division of infectious diseases at Emory University School of Medicine in Atlanta, Georgia, and colleagues report in an article published online June 27 in The Lancet.
Unlike epidermal patches, the microneedle patch studied in this trial penetrates the upper layer of the skin and dissolves rapidly as it delivers the vaccine. The observed efficacy, safety, acceptability, and ease of use of the patch as an immunization modality suggest that its widespread use could enable increased rates of influenza vaccination and reduce the cost of vaccine delivery, the authors write.
For the current study, the researchers enrolled 100 nonpregnant, immunocompetent adults (aged 18 to 49 years) between June 23, 2015, and September 25, 2015. The participants were randomly assigned to one of four treatment groups: healthcare worker-administered inactivated influenza vaccine by microneedle patch, healthcare worker-administered inactivated influenza vaccine by intramuscular injection, healthcare worker-administered placebo by microneedle patch, or self-administered inactivated influenza vaccine by microneedle patch. All of the analyses combined the self-administered and healthcare worker-administered microneedle patch groups.
The researchers compared multiple safety and immunogenicity outcomes, including the incidence of related serious adverse events within 180 days, the incidence of grade 3 solicited or unsolicited adverse events within 28 days, and solicited injection-site and systemic reactions through 7 days postvaccination; new-onset chronic illnesses within 180 days, unsolicited adverse events within 28 days, antibody titres at day 28, and percentages of seroconversion and seroprotection.
“No serious adverse events related to the study products were reported during the study,” the authors report. They note also that there were no withdrawals because of adverse events.
With respect to local and systemic adverse events associated with vaccination, the microneedle patch induced some mild-to-moderate local and systemic reactions but fewer grade 2 and grade 3 events than those observed in patients who received the vaccine intramuscularly (2% vs 12%; P = .02), as well as less injection-site pain (11% vs 44%; P = .05).
However, local injection-site reactions were more common among participants in the two patch groups than those in the intramuscular injection group, including erythema (40% vs zero; P = .0002) and pruritis (82% vs 16%; P < .0001).
“The higher rates of these local events are consistent with previous research with intradermal influenza vaccination,” the authors write. “The reported skin reactions could be due to a local immune response that is visible on the skin surface.”
At 28 days postvaccination, the geometric mean titres and the seroprotection and seroconversion percentages were similar across the three treatment groups for all three viruses in the vaccine (H1N1, H3N2, and B strain). Compared with the placebo group, “seroprotection and seroconversion percentages at day 28 were similar and significantly higher for all three strains contained in the influenza vaccine groups,” they report.
Compared with the immune response to the other flu strains, a weaker response to the influenza B strain was observed in both the patch and intramuscular injection groups, the authors report. They note, however, that a higher proportion of participants who received the patch vaccine achieved seroconversion against the B strain (65% vs 32%; P – .01). “These findings are consistent with previous animal studies showing strong immune responses to skin vaccination with microneedle patches,” Dr Rouphael and colleagues write.
The researchers also compared vaccine dose delivery between the different administration options. The intramuscular vaccination delivered at least 15 µg of each antigen, while mean doses delivered via the patches (as determined through µg measurement of residual antigen levels) were 11.3 µg for the H1N1 strain, 14.4 µg for the H3N2 strain, and 13.1 µg for the B strain.
Of note, there was no significant difference in the dosages delivered through the self-administered and healthcare worker-administered microneedle patches, “suggesting that the participants were able to correctly self-administer microneedle patches,” the authors write.
“After vaccination, imaging of used microneedle patches showed that the microneedles had dissolved in the skin, suggesting that the used patches could be discarded as non-sharps waste,” the authors write. They also note that assessment of vaccine potency following 12 months of storage in desiccated packaging at various temperatures (5°C, 25°C, and 40°C) showed that antigen levels remained within product specifications, “which supports the storage of patches without refrigeration.”
Of the study participants who received the patch-administered vaccination, 96% reported no pain during the application compared with 82% of those who received the vaccine intramuscularly, the authors write. Further, the acceptability of the microneedle administration across all three patch groups was high, ranging from 4.5 to 4.8 on a 5-point scale, compared with a mean acceptability score of 4.4 for the intramuscular group, they note.
Finally, of those who received the vaccine via microneedle patch, 70% stated that they would prefer the delivery method over intramuscular injection or intranasal administration for future vaccinations.
“These results provide evidence that microneedle patch vaccination is an innovative new approach with the potential to improve present vaccination coverage and reduce immunization costs,” the authors conclude.
In an accompanying Comment, Katja Hoschler, PhD, and Maria C. Zambon, PhD, from the Virus Reference Department of the National Infections Service, Public Health England, London, agree, noting, “These early findings suggest the emergence of a promising new option for seasonal vaccination.”
The microneedle patch vaccination option may hold particular promise for the development of national influenza vaccine programs in low-income countries. “In 2014, only 24% of low-income and lower-middle-income countries had influenza immunisation policies compared with 79% of middle-income countries and 92% of high-income countries,” Drs Hoschler and Zambon write. “The [World Health Organization] Global Action Plan for Influenza Vaccines identified the improvement of vaccine delivery as an important development priority and made specific reference to needle-free delivery methods, with their potential to simplify vaccine administration, increase safety, and improve coverage and compliance.”
If late-stage clinical development confirms their efficacy, the microneedle patches also have the potential to become “ideal candidates” for individuals who prefer not to get vaccinated and for the pediatric population, the commenters note. Future studies should consider the immunological mechanisms of the microneedle patch and “should also investigate strategies for antigen sparing and improvement of immunogenicity for vaccines that are delivered through this route.”
The study was funded by the National Institutes of Health.
Three of the authors are inventors on licensed patents and have ownership interest in companies developing microneedle products (Micron Biomedical).
The commentary authors have disclosed no relevant financial relationships.
The Lancet. Published online June 27, 2017. Abstract, Comment
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