A skin immunization strategy might help improve immune protection against flu viruses and reduce mortality rates, according to a study. The delivery of vaccines into skin rather than muscle is known to produce stronger immune protection against some viruses. Yet skin immunization has not been broadly adopted, partly due to relatively high rates of pain and irritation and the difficulty of vaccine administration. Mei Wu and colleagues developed a painless, lesion-free strategy for delivering vaccines into skin using arrays of microneedles, which are separated by sufficient distances to prevent the spread of vaccine-induced inflammation and promote rapid healing. The authors combined this approach with an approved nonablative fractional laser (NAFL) treatment, which provokes a local, transient inflammatory response that augments vaccine-induced immune protection. Mice that received NAFL pretreatment at the inoculation site followed by microneedle-array immunization with an H1N1 influenza vaccine survived exposure to the H1N1 virus, whereas microneedle-array immunization alone protected only 30% of mice. Moreover, the combination strategy conferred a high level of cross-protection against other H1N1 viruses and the H3N2 virus, increasing survival rates compared with microneedle-array immunization alone. Because mismatches often occur between vaccine and circulating strains of viruses, the cross-protection offered by NAFL might enhance vaccine efficacy and reduce death rates during the flu season, according to the authors.