PMID- 32253098 OWN - NLM STAT- MEDLINE DCOM- 20210302 LR - 20210302 IS - 1873-2518 (Electronic) IS - 0264-410X (Linking) VI - 38 IP - 21 DP - 2020 May 6 TI - A grading system for local skin reactions developed for clinical trials of an intradermal and transcutaneous ETEC vaccine. PG - 3773-3779 LID - S0264-410X(20)30323-6 [pii] LID - 10.1016/j.vaccine.2020.02.079 [doi] AB - BACKGROUND: Trials assessing the safety of novel vaccine candidates are essential in the evaluation and development of candidate vaccines. Immunogenicity and dose-sparing features of vaccination approaches which target skin and associated tissues have garnered increased interest; for enteric vaccines, cutaneous vaccination has been of particular interest. Cutaneous vaccine site reactions are among the most common and visible vaccine related adverse events (AEs) when skin routes are used. Regulatory guidelines governing classification of severity focus on functional impact but are insufficient to characterize a spectrum of skin reaction and allow for comparisons of routes, doses and products with similar local cutaneous AEs. OBJECTIVES: Our group developed a grading scale to evaluate and compare cutaneous vaccine site reactions ahead of early-phase clinical trials of intradermal (ID) and transcutaneous immunization (TCI) with enterotoxigenic E.coli (ETEC) vaccine candidates (adhesin-based vaccine co-administered with LTR192G). We reviewed existing methods for characterizing the appearance and severity of local vaccine site reactions following TCI and ID vaccination and devised a standardized vaccine site appearance grading scale (VSAGS) for use in the clinical development of novel ETEC vaccine candidates which focused on pathophysiologic manifestation of skin findings. RESULTS: Available data from published reports revealed erythematous papules and pruritus were the most common local AEs associated with TCI. Frequency of reactions varied notably across studies as did TCI vaccination methodologies and products. ID vaccination commonly results in erythema and induration at the vaccine site as well as pigmentation changes. There was no published methodology to characterize the spectrum of dermatologic findings. CONCLUSION: ID and TCI vaccination are associated with a largely predictable range of cutaneous AEs. A grading scale focused on the appearance of cutaneous changes was useful in comparing cutaneous AEs. A standardized grading scale will facilitate documentation and comparison of cutaneous AEs. CI - Copyright (c) 2020. Published by Elsevier Ltd. FAU - Gutierrez, Ramiro L AU - Gutierrez RL AD - Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States. Electronic address: ramiro.l.gutierrez.mil@mail.mil. FAU - Porter, Chad K AU - Porter CK AD - Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States. Electronic address: chad.k.porter.civ@med.mail.mil. FAU - Jarell, Abel AU - Jarell A AD - Dermatology Department, Walter Reed National Military Medical Center, Bethesda, MD, United States. FAU - Alcala, Ashley AU - Alcala A AD - Enteric Diseases Department, Naval Medical Research Center, Silver Spring, MD, United States. FAU - Riddle, Mark S AU - Riddle MS AD - Uniformed Services University of the Health Sciences, Bethesda, MD, United States. FAU - Turiansky, George W AU - Turiansky GW AD - Uniformed Services University of the Health Sciences, Bethesda, MD, United States. Electronic address: gwturiansky@verizon.net. LA - eng PT - Journal Article DEP - 20200403 PL - Netherlands TA - Vaccine JT - Vaccine JID - 8406899 RN - 0 (Escherichia coli Vaccines) SB - IM MH - Administration, Cutaneous MH - Clinical Trials as Topic MH - Drug-Related Side Effects and Adverse Reactions/*classification MH - Enterotoxigenic Escherichia coli MH - Escherichia coli Vaccines/*adverse effects MH - Humans MH - Immunization MH - Injections, Intradermal/adverse effects MH - Skin/*pathology MH - Vaccination/*adverse effects OTO - NOTNLM OT - Adverse Events OT - Intradermal OT - Transcutaneous OT - Vaccination COIS- Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. EDAT- 2020/04/08 06:00 MHDA- 2021/03/03 06:00 CRDT- 2020/04/08 06:00 PHST- 2018/09/05 00:00 [received] PHST- 2020/02/24 00:00 [revised] PHST- 2020/02/26 00:00 [accepted] PHST- 2020/04/08 06:00 [pubmed] PHST- 2021/03/03 06:00 [medline] PHST- 2020/04/08 06:00 [entrez] AID - S0264-410X(20)30323-6 [pii] AID - 10.1016/j.vaccine.2020.02.079 [doi] PST - ppublish SO - Vaccine. 2020 May 6;38(21):3773-3779. doi: 10.1016/j.vaccine.2020.02.079. Epub 2020 Apr 3.