We conducted a field evaluation using qualitative and quantitative methods to assess freeze prevention of vaccines transported and stored in a recently developed, World Health Organization-prequalified freeze-preventive cold box (FPCB) as compared to currently used standard cold boxes (SCBs). The study assessed the FPCB\'s practical use, health worker acceptance, health system fit (including cost considerations), and challenges faced by health workers in variable conditions and geographical settings. The evaluation took place in five health facilities across hilly and plains districts of Nepal in two phases: Phase 1 involved FPCBs in simulated use alongside SCBs. In Phase 2, actual vaccines were used in the FPCBs. The study gathered quantitative data from logbooks and electronic temperature monitors placed inside and outside the cold boxes. Qualitative data were collected from health workers, cold chain personnel, and immunization program managers involved in the vaccine cold chain at multiple levels. No damage, durability issues, or freezing incidents were observed when using FPCBs, but two incidents of freezing occurred when using SCBs. FPCBs also took longer to cool down than SCBs. Participants mostly found the FPCB to be safe and user friendly for vaccine transportation and short-term storage. Advantages of the FPCB as compared to the SCB include its ability to minimize vaccine wastage, to keep freeze-sensitive vaccines safe (the average value of freeze-sensitive vaccines transported per shipment was $1,704), and to ease preparation through elimination of the need to condition ice packs. Procurement price ranges for FPCBs overlap those for SCBs. Disadvantages of the FPCB include its greater size and weight, which require more personnel and vehicles during transportation. This suggests that lighter and smaller FPCBs would be more effective and acceptable for the Nepal immunization program and other, similar immunization programs conducted globally.

The high-density microneedle array patch (HD-MAP) is a novel vaccine delivery system with potential for self-administered vaccination. In this study, Vaxxas HD-MAPs were applied by both a trained user and self-administered with application sites compared to determine the response of skin and the level of engagement of the HD-MAP with human skin. Twenty healthy participants were enrolled, and the response of skin including erythema was observed at all application sites and no difference was found between trained user or self-administered applications. The majority of participants (70%) preferred the deltoid upper arm application site for applying HD-MAPs. Fluorescent dermatoscope images confirmed HD-MAPs engaged the skin surface and scanning electron microscopy (SEM) image analysis exhibited similar delivery characteristics for the upper arm and forearm sites when applied by either a trained user or self-administered. This study showed that noninvasive methods including dermatoscopy and SEM image analysis were able to estimate the engagement of HD-MAPs with human skin. HD-MAP self-vaccination technology has a unique proposition in pandemic preparedness by alleviating the need for health-care workers to administer vaccines, however greater awareness and understanding of the potential of this technology is required.

To evaluate the impact of a multi-component intervention package of maternal immunization uptake in obstetric care clinics.
In a multi-level, cluster- and individually-randomized controlled trial we implemented an evidence-based intervention that targeted practice-, provider- and patient-level barriers to vaccine uptake. Obstetric practices were randomized to receive the practice and provider-level interventions or continue their normal standard of care. We enrolled pregnant women at practices in Georgia and Colorado and randomized women into patient-level intervention and control groups, resulting in four study arms. The primary outcomes were receipt of the influenza and tetanus, diphtheria and acellular pertussis (Tdap) vaccines during pregnancy. A sample size of 550 women per arm (2200 total) was planned and enrolled to compare the intervention between the four study arms.
Between June 2017 and July 2018, 4907 women were screened and 2200 women were randomized, 550 to each of the four study arms. We were unable to follow-up with 108 women, for a final sample size of 2092. Sample characteristics and sample size were similar among study arms. There was no significant increase in Tdap or influenza vaccine uptake overall. Among women who had no intention of or were unsure about receiving the influenza vaccine during pregnancy, those who received just the patient-level intervention were 61% more likely to receive the influenza vaccine than those in the control arm (Relative risk: 1.61; 95% Confidence Interval: 1.18-2.21). There was no significant difference in vaccine uptake for either influenza or tetanus, diphtheria and acellular pertussis between the four arms of the study.
This trial highlights the need for more targeted interventions to improve vaccine uptake. Future work should focus on clinics with low baseline vaccine uptake and the patient-level intervention should be expanded and targeted towards women with low vaccine confidence.

Photochemical internalization (PCI) is a technology for inducing release of endocytosed antigens into the cell cytosol via a light-induced process. Preclinical experiments have shown that PCI improves MHC class I antigen presentation, resulting in strongly enhanced CD8+ T-cell responses to polypeptide antigens. In PCI vaccination a mixture of the photosensitizing compound fimaporfin, vaccine antigens, and an adjuvant is administered intradermally followed by illumination of the vaccination site. This work describes an open label, phase I study in healthy volunteers, to assess the safety, tolerability, and immune response to PCI vaccination in combination with the adjuvant poly-ICLC (Hiltonol) (ClinicalTrials.gov Identifier: NCT02947854).
The primary objective of the study was to assess the safety and local tolerance of PCI mediated vaccination, and to identify a safe fimaporfin dose for later clinical studies. A secondary objective was to analyze the immunological responses to the vaccination. Each subject received 3 doses of HPV16 E7 peptide antigens and two doses of Keyhole Limpet Hemocyanin (KLH) protein. A control group received Hiltonol and vaccine antigens only, whereas the PCI groups in addition received fimaporfin + light. Local and systemic adverse effects were assessed by standard criteria, and cellular and humoral immune responses were analyzed by ELISpot, flow cytometry, and ELISA assays.
96 healthy volunteers were vaccinated with fimaporfin doses of 0.75-50 µg. Doses below 17.5 µg were safe and tolerable, higher doses exhibited local tolerability issues in some study subjects, mainly erythema, and pain during illumination. There were few, and only mild and expected systemic adverse events. The employment of PCI increased the number of subjects exhibiting a T-cell response to the HPV peptide vaccine about 10-fold over what was achieved with the antigen/Hiltonol combination without PCI. Moreover, the use of PCI seemed to result in a more consistent and multifunctional CD8+ T-cell response. An enhancement of the humoral immune response to KLH vaccination was also observed.
Using PCI in combination with Hiltonol for intradermal vaccination is safe at fimaporfin doses below 17.5 µg, and gives encouraging immune responses to peptide and protein based vaccination.

UNASSIGNED: The development of oral vaccine formulations has been widely investigated to overcome oral route problems. This research investigated the in vivo immune response of ovalbumin-alginate microspheres by uptake compared with a commercial oral vaccine product.
UNASSIGNED: Ovalbumin-loaded alginate microspheres were prepared using aerosolization. Ovalbumin antigen in vivo uptake was investigated in order to understand the distribution and uptake by Peyer\'s plaque (PP) after oral administration using fluorescence microscopy. The histopathology of ovalbumin-alginate microspheres in the liver and kidney was also investigated.
UNASSIGNED: The use of alginate microspheres to deliver vaccines could be a promising delivery system for the development of oral vaccines because uptake by PP is an essential step in oral vaccination.
UNASSIGNED: Fluorescence visualization revealed the uptake of ovalbumin-loaded alginate microspheres with and without lyoprotectant maltodextrin by PP was equal to the oral vaccine product and no liver or kidney damage was found.