Integrated antibody and cellular immunity monitoring are required for assessment of the long term protection that will be essential for effective next generation vaccine development.

The COVID pandemic exposed the critical role T cells play in initial immunity, the establishment and maintenance of long term protection, and of durable responsiveness against novel viral variants. A growing body of evidence indicates that adding measures of cellular immunity will fill an important knowledge gap in vaccine clinical trials, likely leading to improvements in the effectiveness of the next generation vaccines against current and emerging variants. In depth cellular immune monitoring in Phase II trials, particularly for high risk populations such as the elderly or immune compromised, should result in better understanding of the dynamics and requirements for establishing effective long term protection. Such analyses can result in cellular immunity correlates that can then be deployed in Phase III studies using appropriate, scalable technologies. Measures of cellular immunity are less established than antibodies as correlates of clinical immunity, and some misconceptions persist about cellular immune monitoring usefulness, cost, complexity, feasibility, and scalability. We outline the currently available cellular immunity assays, review their readiness for use in clinical trials, their logistical requirements, and the type of information each assay generates. The objective is to provide a reliable source of information that could be leveraged to develop a rational approach for comprehensive immune monitoring during vaccine development.

The need for more holistic immune profiling in next-generation SARS-CoV-2 vaccine trials.

First-generation anit-SARS-CoV-2 vaccines were highly successful. They rapidly met an unforeseen emergency need, saved millions of lives, and simultaneously eased the burden on healthcare systems worldwide. The first-generation vaccines, however, focused too narrowly on antibody-based immunity as the sole marker of vaccine trial success, resulting in large knowledge gaps about waning vaccine protection, lack of vaccine robustness to viral mutation, and lack of efficacy in immunocompromised populations. Detailed reviews of first-generation vaccines, including their mode of action and geographical distribution, have been published elsewhere. Second-generation clinical trials must address these gaps by evaluating a broader range of immune markers, including those representing cell-mediated immunity, to ensure the most protective and long-lasting vaccines are brought to market.

Cellular Immunity Is Critical for Assessing COVID-19 Vaccine Effectiveness in Immunocompromised Individuals.

COVID-19 vaccine clinical development was conducted with unprecedented speed. Immunity measurements were concentrated on the antibody response which left significant gaps in our understanding how robust and long-lasting immune protection develops. Better understanding the cellular immune response will fill those gaps, especially in the elderly and immunocompromised populations which not only have the highest risk for severe infection, but also frequently have inadequate antibody responses. Although cellular immunity measurements are more logistically complex to conduct for clinical trials compared to antibody measurements, the feasibility and benefit of doing them in clinical trials has been demonstrated and so should be more widely adopted. Adding significant cellular response metrics will provide a deeper understanding of the overall immune response to COVID-19 vaccination, which will significantly inform vaccination strategies for the most vulnerable populations. Better monitoring of overall immunity will also substantially benefit other vaccine development efforts, and indeed any therapies that involve the immune system as part of the therapeutic strategy.

Descriptive analysis of primary package labels from commercially available prescription solid oral dosage form drugs.

OBJECTIVE: To describe formats used by manufacturers to display drug names on primary package labels for prescription solid oral dosage forms. DESIGN: Cross-sectional study. SETTING: Independent community pharmacy in rural Indiana. The images were collected in February 2006. PARTICIPANTS: Not applicable. INTERVENTION: High-resolution digital photos were taken of 918 primary package labels (422 brand name and 496 generic) from all solid oral dosage forms stocked in an independent community pharmacy. We coded the images for the presence or absence of specific typographical characteristics used to distinguish the name of the drug. We also coded for the presence or absence of an image of the product on the label. MAIN OUTCOME MEASURES: Frequency of various typographical characteristics used to display the drug name(s) on a primary package label. RESULTS: Manufacturers use a wide variety of techniques to increase the distinctiveness of drug names on primary package labels, including color, boldface, underlining, italics, capitalization, highlighting, use of abbreviations, and use of parentheses to differentiate the generic name of the drug, as well as use of images of the drug product. The frequency of use of the different techniques varied substantially (e.g., boldface fonts used in nearly 98% of brand-name labels, underlining used in only 0.2% of brand-name labels). The frequency of use of the techniques differed across brand and generic products. CONCLUSION: The lack of standardization in the typographical presentation of drug names on primary package labels of solid oral dosage forms in the United States appears to reflect underlying uncertainty about the relative effectiveness of the different techniques. Given the frequency and severity of wrong drug errors caused, at least in part, by the inability of clinicians to distinguish between similar labels, research is urgently needed to determine which technique or combination of techniques will minimize the risk of confusion.