Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1 log10(TCID50) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection.

Per‐ and polyfluoroalkyl substances (PFAS) have emerged as contaminants of environmental concern following release from industrial practices and use of aqueous film–forming foam (AFFF). Of the identified PFAS in surface water samples from known AFFF release sites, perfluorooctanesulfonate (PFOS) and perfluorohexanesulfonic acid (PFHxS) are frequently detected. The focus of the present study was to determine the effects of PFOS and PFHxS to the native (and common) fathead minnow, Pimephales promelas, over critical life stages of reproduction and development. Two separate, 42‐d experiments were carried out using sexually mature fish, exposed to either PFOS or PFHxS. Measured exposure concentrations for PFOS and PFHxS were 0, 44, 88, 140, and 231 µg/L and 0, 150, 300, 600, and 1200 µg/L, respectively. At day 21 of the adult exposure, eggs were collected and reared for 21 d to determine the effects of PFOS or PFHxS on development, growth, and survival of larvae. The no‐observable‐effect concentration (NOEC) for PFOS was 44 µg/L, and the lowest‐observable‐effect concentration was 88 µg/L based on reduced growth in juvenile (F1) fish. Effects from PFOS exposures that did not follow a standard dose–response curve were reduced gonadosomatic index in adult males (at 44 µg/L) and reduced fecundity in females (at 140 µg/L). There was no toxicity on apical endpoints to report on adult or juvenile fish exposed to PFHxS up to 1200 µg/L. Importantly, we note that both PFOS and PFHxS accumulated in gonads and liver of adult fish following the respective exposures. The present study supports previous literature on PFOS toxicity and accumulation in fathead minnows but resulted in a lower NOEC than previously established for this species. Environ Toxicol Chem 2021;40:811–819. © 2020 SETAC

Animal models are critical to the advancement of our knowledge of infectious disease pathogenesis, diagnostics, therapeutics, and prevention strategies. The use of animal models requires thoughtful consideration for their well-being, as infections can significantly impact the general health of an animal and impair their welfare. Application of the 3Rs—replacement, refinement, and reduction—to animal models using biohazardous agents can improve the scientific merit and animal welfare. Replacement of animal models can use in vitro techniques such as cell culture systems, mathematical models, and engineered tissues or invertebrate animal hosts such as amoeba, worms, fruit flies, and cockroaches. Refinements can use a variety of techniques to more closely monitor the course of disease. These include the use of biomarkers, body temperature, behavioral observations, and clinical scoring systems. Reduction is possible using advanced technologies such as in vivo telemetry and imaging, allowing longitudinal assessment of animals during the course of disease. While there is no single method to universally replace, refine, or reduce animal models, the alternatives and techniques discussed are broadly applicable and they should be considered when infectious disease animal models are developed.

Because human patients with monkeypox virus (MPXV) infection report painful symptoms, it is reasonable to assume that animals infected with MPXV experience some degree of pain. Understanding whether and how analgesics affect MPXV disease progression is crucial when planning in vivo challenge experiments. In the current study, we challenged prairie dogs with a low dose (4 × 10 3 pfu) of MPXV and treated with meloxicam (NSAID) or buprenorphine (opioid); control animals did not receive analgesia or received analgesia without MPXV challenge. Subsets of animals from each group were serially euthanized during the course of the study. Disease progression and viral kinetics were similar between groups, but MXPVinfected, meloxicam-treated animals showed increasing trends of morbidity and mortality compared with other groups. Differences between no-analgesia MPXV-infected control animals and MPXV-infected animals treated with buprenorphine were minimal. The findings in the current study allow more informed decisions concerning the use of analgesics during experimental MPXV challenge studies, thereby improving animal welfare. In light of these findings, we have modified our pain scale for this animal model to include the use of buprenorphine for pain relief when warranted after MPXV challenge.