key: cord-1035267-hdg2yxmp authors: Fernandez‐Nieto, Diego; Ortega‐Quijano, Daniel; Jimenez‐Cauhe, Juan; Burgos‐Blasco, Patricia; Bea‐Ardebol, Sonia title: COVID‐19 vaccination challenge: history lessons from a dermatologist’s perspective date: 2021-03-04 journal: Int J Dermatol DOI: 10.1111/ijd.15449 sha: b44ea069c242172b22a0e99557dc0ef58d489ede doc_id: 1035267 cord_uid: hdg2yxmp nan In this constantly evolving globalized world, there are some lessons from prevaccination times which can be considered for modern-day challenges, including variolation administration routes and elicited immune responses. Like smallpox, COVID-19 can also induce vesicular "varicella-like" rashes. [4] [5] [6] However, the presence of viral particles has not been identified inside the vesicles, so a potential SARS-CoV-2 variolation appears unfeasible. 6 Variolation, also known as inoculation, was the first method used to immunize an individual against smallpox. It induced a usually mild form of the disease with a rapid onset. Mortality rate was estimated to be 2-3% compared to 20-30% from an ordinary infection. 7 The earliest documented writing about variolation dates from 1549 in China. However, it is thought that this practice has been performed since ancient times in both China and India, as a mixture of medicine, magic, and religion with an oral transmission. The Chinese implemented a method of nasal insufflation. Mild smallpox cases were selected as donors, whose dry scabs were ground into powder or mixed with a variety of herbs. This "pocky matter" was carried at body temperature for a month or exposed to hot steam before its use. It was then inoculated up the nose with a silver blowpipe. 7 The nasal route for immunization is considered as a straightforward approach to induce potent immune responses, particularly at the lung mucosa. 8 Experimental SARS-CoV/MERS-CoV vaccines led to attractive correlates of protection, even higher than those achieved by parenteral vaccines. 9 This type of mucosal immunization has proven to induce specific SARS-CoV secretory IgA production in both the upper respiratory tract and lungs. 10 Major challenges for mucosal vaccines include the requirement of higher antigen doses, the need for effective and safe mucosal adjuvants, and the difficulties to elicit significant immune responses, as the default response is tolerance, especially toward soluble or subunit antigens. AdCOVID, an intranasal ª 2021 the International Society of Dermatology International Journal of Dermatology 2021 Immune responses in COVID-19 and potential vaccines: lessons learned from SARS and MERS epidemic mRNA as a transformative technology for vaccine development to control infectious diseases Developing a vaccine for covid-19 Classification of the cutaneous manifestations of COVID-19: a rapid prospective nationwide consensus study in Spain with 375 cases Varicella-like exanthem as a specific COVID-19-associated skin manifestation: Multicenter case series of 22 patients Clinical and histological characterization of vesicular COVID-19 rashes: a prospective study in a tertiary care hospital The origins of inoculation Subunit-based mucosal vaccine delivery systems for pulmonary delivery -Are they feasible? Nasal route for vaccine and drug delivery: features and current opportunities Effect of mucosal and systemic immunization with virus-like particles of severe acute respiratory syndrome coronavirus in mice Single-dose intranasal administration of AdCOVID elicits systemic and mucosal immunity against SARS-CoV-2 in mice The immunological anatomy of the skin