Case Report Intradermal ChAdOx1 Vaccine Following Two CoronaVac Shots: A Case Report Ekachai Singhatiraj 1, Krit Pongpirul 1,2,3,* , Anan Jongkaewwattana 4 and Nattiya Hirankarn 5 1 Department of Medicine, Bumrungrad International Hospital, Bangkok 10110, Thailand; [email protected] 2 Department of Preventive and Social Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand 3 Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD 21205, USA 4 National Center for Genetic Engineering and Biotechnology (BIOTEC), National Science and Technology Development Agency (NSTDA), Pathumthani 12120, Thailand; [email protected] 5 Center of Excellence in Immunology and Immune-Mediated Diseases, Department of Microbiology, Faculty of Medicine, Chulalongkorn University, Bangkok 10330, Thailand; [email protected] * Correspondence: [email protected] Abstract: Inactivated SARS-CoV-2 vaccines are used in many countries with uncertain immunogenic- ity. Intradermal ChAdOx1 has been proposed as a resource-efficient heterologous third booster shot. A 52-year-old healthy male healthcare professional had received two intramuscular CoronaVac shots on 21 April and 23 May 2021, and volunteered to take a 0.1 mL ChAdOx1 vaccine intradermally on 29 June 2021, with minimal local reactions. The declining IgG levels against spike protein from the two CoronaVac shots increased to higher than 10,000 AU/mL two weeks after the intradermal Citation: Singhatiraj, E.; Pongpirul, ChAdOx1. Moreover, the neutralizing antibody increased from 66.77% to almost 100%. A ratio of K.; Jongkaewwattana, A.; Hirankarn, 6.6:9.7 of IgA:IgG was observed. The 50% pseudovirus neutralization titer (PVNT50) against lentiviral N. Intradermal ChAdOx1 Vaccine pseudovirus bearing a codon-optimized spike gene (wild type, alpha, beta, and delta) were 1812.42, Following Two CoronaVac Shots: A 822.99, 1025.42, 1347.13, respectively. The SARS-CoV-2-specific T cells to spike protein–peptide pools Case Report. Vaccines 2021, 9, 990. (532–788 SFU/106 PBMCs) were detected. In conclusion, the antibody and cellular responses to the https://doi.org/10.3390/ intradermal ChAdOx1, as a third booster dose in a healthy volunteer who received two intramuscular vaccines9090990 CoronaVac shots, revealed a dramatic increase in the total antibodies, including IgG, IgA, as well as T cell responses against spike protein. The immune response from intradermal ChAdOx1 should be Academic Editors: Ralph A. Tripp, further investigated in a larger population. Steven B. Bradfute and Scott Anthony Keywords: COVID-19 vaccines; ChAdOx1-S; CoronaVac; intradermal injections; intramuscular injections Received: 3 August 2021 Accepted: 1 September 2021 Published: 4 September 2021 Publisher’s Note: MDPI stays neutral 1. Introduction with regard to jurisdictional claims in Inactivated SARS-CoV-2 vaccines have been used worldwide, especially in low- and published maps and institutional affil- middle-income countries (LMICs), under emergency use. While the conclusive results from iations. at least 16 phases I/phase II/phase III trials have not yet been available [1], the findings from a large observational study in Chile revealed that the effectiveness of CoronaVac (Sinovac Biotech, Beijing, China) after one course of two 0.5 mL intramuscular injections was 65.9% in preventing symptomatic disease, 87.5% for hospitalization, 90.3% for ICU Copyright: © 2021 by the authors. admission, and 86.3% in reducing mortality [2]. The study findings suggested that a third Licensee MDPI, Basel, Switzerland. booster might be needed. Nonetheless, it should be noted that the efficacy of CoronaVac in This article is an open access article alleviating disease severity and reducing mortality has been inconsistent, mainly because distributed under the terms and of the variant composition in different countries. conditions of the Creative Commons A recent review reported a range of 60% to 94% efficacies of different COVID-19 Attribution (CC BY) license (https:// vaccine platforms [3]. The currently available data suggested lower antibody responses to creativecommons.org/licenses/by/ the inactivated virus and viral-vectored vaccines than to the mRNA and protein subunit 4.0/). Vaccines 2021, 9, 990. https://doi.org/10.3390/vaccines9090990 https://www.mdpi.com/journal/vaccines Vaccines 2021, 9, x FOR PEER REVIEW 2 of 6 inactivated virus and viral-vectored vaccines than to the mRNA and protein subunit vac- cines [3]. Multiple approaches to achieve the goal of an effective vaccination are pragmat- Vaccines 2021, 9, 990 ically important [3]. 2 of 6 As an alternative for immune response enhancement, a heterologous prime-boost strategy has been proposed to elicit both humoral and cell-mediated immune responses vaccinesthat could [3]. lead Multiple to robust, approaches broad, to achieve and lo theng-lasting goal of animmunity. effective vaccination For instance, are in the pragmaticallyCombiVacS trial, important healthy [3]. individuals who received ChAdOx1-S (Vaxzevria, Cambridge, AstraZeneca,As an alternative UK), followed for immune with response the BNT enhancement,162b2 (Comirnaty, a heterologous BioNTech, prime-boost Mainz, Ger- strategymany), hasproduced been proposed substantially to elicit higher both humoral levels andof antibodies cell-mediated than immune the control responses group [4]. thatNonetheless, could lead tomore robust, evidence broad, andis requ long-lastingired to prove immunity. this Forspeculation. instance, in the CombiVacS trial, healthyThe fluctuating individuals supplies who received of the ChAdOx1-S various coronavirus (Vaxzevria, vaccines Cambridge, increase AstraZeneca, the likelihood UK), followed with the BNT162b2 (Comirnaty, BioNTech, Mainz, Germany), produced of the heterologous vaccination strategy and introduce a potential use of a fractional dos- substantially higher levels of antibodies than the control group [4]. Nonetheless, more evidenceing scheme is required in mass to vaccination prove this speculation. campaigns in resource-limited settings [5]. As Thailand’s initialThe plan fluctuating for the supplies domestic of the manufacture various coronavirus and distribution vaccines increase of ChAdOx1 the likelihood was of delayed, theCoronaVac heterologous has vaccinationbeen given strategy to most and of the introduce population, a potential including use of a healthcare fractional dosing professionals. schemeGiven the in mass comparable vaccination immunogenicity campaigns in resource-limited between the settings low-dose [5]. intradermal As Thailand’s and initial standard- plandose for intramuscular the domestic manufactureadministration and of distribution the influe ofnza ChAdOx1 vaccine was[6], delayed,along with CoronaVac relatively fewer hassystematic been given side to effects most of [5], the intradermal population, including ChAdOx1 healthcare has been professionals. proposed as Given a third the heterolo- comparablegous booster. immunogenicity between the low-dose intradermal and standard-dose intra- muscular administration of the influenza vaccine [6], along with relatively fewer systematic side effects [5], intradermal ChAdOx1 has been proposed as a third heterologous booster. 2. Case Presentation 2. CaseA Presentation52-year-old healthy male healthcare professional had received two intramuscular CoronaVacA 52-year-old shots healthyon 21 April male healthcareand 23 May professional 2021. He had did received not experience two intramuscular any notable side CoronaVaceffects from shots the onvaccination. 21 April and He 23 had May never 2021. been He infected did not experience with the SAR-CoV-2 any notable virus. side Before effectsthe vaccination, from the vaccination. his blood He tested had nevernegative been fo infectedr IgM withand theIgG SAR-CoV-2 by the SARS-CoV-2 virus. Before antibody thechemiluminescent vaccination, his blood microparticle tested negative immunoassay for IgM and (CMIA). IgG by the SARS-CoV-2 antibody chemiluminescent microparticle immunoassay (CMIA). His serum tested for the SARS-CoV-2 spike IgG antibody (Abbott Laboratories, IL, His serum tested for the SARS-CoV-2 spike IgG antibody (Abbott Laboratories, IL, USA)USA) on on 17 17 June June (57 (57 and and 25 days25 days after after the first the and first second and second doses, respectively), doses, respectively), revealing arevealing levela level of 853.6 of 853.6 AU/mL, AU/mL, whereas whereas the SARS-CoV-2 the SARS-CoV-2 surrogate virus surrogate neutralization virus test neutralization (cPass™, test GenScript,(cPass™, GenScript, NJ, USA) reported NJ, USA) 66.77% reported (Figure 66.77%1). The IgG(Figure antibody 1). The decreased IgG antibody to 690.7 anddecreased to 640.2690.7 AU/mL and 640.2 on AU/mL 1 and 6 July on 1 (39 and and 6 44July days (39 after and the44 seconddays after dose, the respectively), second dose, whereas respectively), thewhereas neutralization the neutralization test reduced test to 57.16% reduced and to 51.30%, 57.16% respectively. and 51.30%, respectively. FigureFigure 1. 1.Spike Spike immunoglobulin immunoglobulin G and G and neutralizing neutralizing antibody anti levelsbody afterlevels the after two the intramuscular two intramuscular CoronaVacCoronaVac vaccinations vaccinations and and one one intradermal intradermal ChAdOx1 ChAd vaccination.Ox1 vaccination. The green The bar green graphs bar present graphs present neutralizingneutralizing antibody antibody levels levels (%) (%) whereas whereas the blue the