Safety and Immunogenicity of Intradermal Fractional Dose Administration of the mRNA-1273 Vaccine: A Proof-of-Concept Study

Roozen, Geert V.T.; Prins, Margaretha; Binnendijk, Rob van; Hartog, Gerco den; Kuiper, Vincent P; Prins, Corine; Janse, Jacqueline J.; Kruithof, Annelieke C.; Feltkamp, Mariet C.W.; Kuijer, Marjan; Rosendaal, Frits R.; Roestenberg, Meta; Visser, Leo G.; Roukens, Anna H E

doi:10.7326/m22-2089

Cited by 15 publications

(16 citation statements)

References 3 publications

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“…The dermis is rich in APCs and ID vaccination can typically achieve equivalent or superior immune responses than vaccination through IM or SC (16,17). ID administration of low-dose regimens (10-20 µg) of mRNA-1273 were found to be safe and well tolerated, and induced robust antibody responses that were comparable to standard 100 µg mRNA-1273 IM regimens (4). Whilst immunogenic, ID administration of 20% standard IM BNT162b2 dosage as a booster induced lower antibody and cellular immune responses compared to standard IM administration in individuals previously vaccinated with CoronaVac as a primary series (2).…”

Section: Discussionmentioning

confidence: 99%

“…Intradermal (ID) injection, or the administration of drugs into the dermis, is an alternative method of vaccination to conventional intramuscular (IM) or subcutaneous (SC) routes (1, 2). The dermis and epidermis are rich in antigen-presenting cells (or APCs, i.e., dermal dendritic cells [DDCs]), that dramatically enhance innate and adaptative immune responses (1, [3][4][5][6][7]. Fractional doses 10-20% of their IM or SC dosages are generally used for ID administration (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

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Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations

et al. 2023

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IntroductionThis phase I study explored the immunogenicity and reactogenicity of accelerated, Q7 fractional, intradermal vaccination regimens for COVID-19.MethodsParticipants (n = 60) aged 18-60 years, naïve to SARS-CoV-2 infection or vaccination, were randomly allocated into one of four homologous or heterologous accelerated two-dose, two-injection intradermal regimens seven days apart:(1) BNT162b2-BNT162b2(n= 20),(2) ChAdOx1- BNT162b2 (n = 20), (3) CoronaVac-ChAdOx1 (n = 10), and (4) ChAdOx1-ChAdOx1 (n = 10). CoronaVac and ChAdOx1 were 20%, and BNT162b2 17%, of their standard intramuscular doses (0.1 mL and 0.05 mL per injection, respectively). Humoral immune responses were measured through IgG response towards receptor binding domains (RBD-IgG) of ancestral SARS-CoV-2 spike protein and pseudovirus neutralization tests (PVNT50). Cellular immune responses were measured using ELISpot for ancestral protein pools.ResultsImmunogenicity was highest in regimen (2), followed by (1), (4), and (3) 2 weeks after the second dose (P < 0.001 for anti-RBD-IgG and P= 0.01 for PVNT50). Each group had significantly lower anti-RBD IgG (by factors of 5.4, 3.6, 11.6, and 2.0 for regimens (1) to (4), respectively) compared to their respective standard intramuscular regimens (P < 0.001 for each). Seroconversion rates for PVNT50 against the ancestral strain were 75%, 90%, 57% and 37% for regimens (1) to (4), respectively. All participants elicited ELISpot response to S-protein after vaccination. Adverse events were reportedly mild or moderate across cohorts.DiscussionWe concluded that accelerated, fractional, heterologous or homologous intradermal vaccination regimens of BNT162b2 and ChAdOx1 were well tolerated, provided rapid immune priming against SARS-CoV-2, and may prove useful for containing future outbreaks.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations

et al. 2023

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“…The use of adjuvants and the route of administration are known to influence the immune response to vaccination [ 86 ]. With reference to the latter, the intradermal administration of the influenza vaccine in KTRs has been shown to improve immunisation [ 86 ], most likely due to the greater number of antigen-presenting cells in the skin than in muscle [ 87 , 88 ].…”

Section: Strategies For More Robust Protection Against Covid-19 For C...mentioning

confidence: 99%

What has vaccination against COVID-19 in CKD patients taught us?

2023

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Effective vaccination strategies are of crucial importance to protecting patients who are vulnerable to infections, such as patients with chronic kidney disease. This is because the decreased efficiency of the immune system in chronic kidney disease impairs vaccine-induced immunisation. COVID-19 has prompted investigation of the immune response to SARS-CoV-2 vaccines in chronic kidney disease and in kidney transplant recipients in an effort to improve efficacy. The seroconversion rate after two vaccine doses is reduced, especially in kidney transplant recipients. Furthermore, although the seroconversion rate in chronic kidney disease patients is as high as in healthy subjects, anti-spike antibody titres are lower than in healthy vaccinated individuals, and these titres decrease rapidly. Although the vaccine-induced anti-spike antibody titre correlates with neutralising antibody levels and with protection against COVID-19, the protective prognostic significance of their titre is decreased due to the emergence of SARS-CoV-2 variants other than the Wuhan index virus against which the original vaccines were produced. Cellular immunity is also relevant, and because of cross-reactivity to the spike protein, epitopes of different viral variants confer protection against newly emerging variants of SARS-CoV-2. A multi-dose vaccination strategy is the most effective way to obtain a sufficient serological response. In kidney transplant recipients, a 5-week discontinuation period from antimetabolite drugs in concomitance with vaccine administration may also increase the vaccine’s efficacy. The newly acquired knowledge obtained from COVID-19 vaccination is of general interest for the success of other vaccinations in chronic kidney disease patients.

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“…doses and 2 full-dose i.m. delivery of the mRNA-1273 (Moderna) vaccine, each 28 days apart, as a primary vaccination series [ 28 ]. Fractional dosing through i.d.…”

Section: Introductionmentioning

confidence: 99%

Coagulation and inflammatory response after intramuscular or intradermal mRNA-1273 SARS-CoV-2 vaccine: secondary analysis of a randomized trial

van Dijk,

Prins,

Roukens

et al. 2024

Research and Practice in Thrombosis and Haemostasis

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Safety and Immunogenicity of Intradermal Fractional Dose Administration of the mRNA-1273 Vaccine: A Proof-of-Concept Study

Cited by 15 publications

References 3 publications

Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations

Immunogenicity and reactogenicity of accelerated regimens of fractional intradermal COVID-19 vaccinations

What has vaccination against COVID-19 in CKD patients taught us?

Coagulation and inflammatory response after intramuscular or intradermal mRNA-1273 SARS-CoV-2 vaccine: secondary analysis of a randomized trial

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