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Immunogenicity and safety of an intradermal ChAdOx1 nCoV-19 boost in a healthy population.

ABSTRACT: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Two doses of an inactivated SARS-CoV-2 vaccine (CoronaVac) have been shown to be insufficient to protect against variants of concern (VOCs), while viral vector vaccines remain protective against the infection. Herein, we conducted a preliminary study to evaluate the safety and immunity in an adult population who received the conventional 2 dosage-regimen of inactivated SARS-CoV-2 vaccine; with an additional intradermal ChAdOx1 nCoV-19 reciprocal dosage (1:5). An Intramuscular ChAdOx1 nCoV-19 booster was also included as a control. Immediate and delayed local reactions were frequently observed in the fractional intradermal boost, but systemic side effects were significantly decreased compared to the conventional intramuscular boost. The anti-RBD-IgG levels, the neutralising function against delta variants, and T cell responses were significantly increased after boosting via both routes. Interestingly, the shorter interval elicited higher immunogenicity compared to the extended interval. Taken together, a reciprocal dosage of intradermal ChAdOx1 nCoV-19 booster reduces systemic adverse reactions and enhances non inferiority humoral and cellular immune responses compared to a full dose of intramuscular boosting. These findings provide for an effective vaccine management during the shortages of vaccine supply.

SUBMITTER: Pinpathomrat N

PROVIDER: S-EPMC9106663 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Immunogenicity and safety of an intradermal ChAdOx1 nCoV-19 boost in a healthy population.

Pinpathomrat Nawamin N Intapiboon Porntip P Seepathomnarong Purilap P Ongarj Jomkwan J Sophonmanee Ratchanon R Hengprakop Jariya J Surasombatpattana Smonrapat S Uppanisakorn Supattra S Mahasirimongkol Surakameth S Sawaengdee Waritta W Phumiamorn Supaporn S Sapsutthipas Sompong S Kongkamol Chanon C Ingviya Thammasin T Sangsupawanich Pasuree P Chusri Sarunyou S

NPJ vaccines 20220513 1

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a global pandemic. Two doses of an inactivated SARS-CoV-2 vaccine (CoronaVac) have been shown to be insufficient to protect against variants of concern (VOCs), while viral vector vaccines remain protective against the infection. Herein, we conducted a preliminary study to evaluate the safety and immunity in an adult population who received the conventional 2 dosage-regimen of inactivated SARS-CoV-2 vaccine; with an additiona ...[more]

PMID: 35562372

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Project description:There is a limited supply of COVID-19 vaccines, with less than 20% of eligible populations in low-income countries having received one dose. Intradermal delivery of fractional dose vaccines is one way to improve global vaccine access, but no studies have reported data on intradermal delivery of COVID-19 primary series vaccination. We conducted a pilot study to examine the safety and immunogenicity of three intradermal primary series regimens - heterologous regimen of CoronaVac and ChAdOx1 (CoronaVac-ChAdOx1), homologous regimen of ChAdOx1 (ChAdOx1-ChAdOx1), and homologous regimen of BNT162b2 (BNT162b2-BNT162b2). Each dose was 1/5th or 1/6th of the standard dose. Two additional exploratory arms of intradermal vaccination for the second dose following an intramuscular first dose of ChAdOx1 and BNT162b2 were included. Intradermal vaccination was found to be immunogenic and safe. The antibody responses generated by the intradermal primary series were highest in the BNT162b2 arms. The anti-receptor binding domain (anti-RBD) IgG concentration following fractional dose intradermal vaccination was similar to that of standard dose intramuscular vaccination of the same regimen for all study arms except for BNT162b2. The BNT162b2 intradermal series generated a lower antibody concentration than the reference intramuscular series, despite generating the highest antibody concentration of all three intradermal primary series regimens. Neutralizing antibody responses against the SARS-CoV-2 ancestral strain were consistent with what was observed for anti-RBD IgG, with lower titers for SARS-CoV-2 variants. Neutralizing titers were lowest against the omicron variant, being undetectable in about a quarter of study participants. T-cell responses against spike- and nucleocapsid-membrane-open reading frame proteins were also detected following intradermal vaccination. Adverse effects following intradermal vaccination were generally comparable with post-intramuscular vaccination effects. Taken together, our data suggest that intradermal vaccination using 1/5th or 1/6th of standard COVID-19 intramuscular vaccination dosing were immunogenic with tendency of lower systemic adverse reactions than intramuscular vaccination. Our findings have implications in settings where COVID-19 vaccines are in shortage.

Project description:BackgroundHeterologous vaccine regimens have been widely discussed as a way to mitigate intermittent supply shortages and to improve immunogenicity and safety of COVID-19 vaccines. We aimed to assess the reactogenicity and immunogenicity of heterologous immunisations with ChAdOx1 nCov-19 (AstraZeneca, Cambridge, UK) and BNT162b2 (Pfizer-BioNtech, Mainz, Germany) compared with homologous BNT162b2 and ChAdOx1 nCov-19 immunisation.MethodsThis is an interim analysis of a prospective observational cohort study enrolling health-care workers in Berlin (Germany) who received either homologous ChAdOx1 nCov-19 or heterologous ChAdOx1 nCov-19-BNT162b2 vaccination with a 10-12-week vaccine interval or homologous BNT162b2 vaccination with a 3-week vaccine interval. We assessed reactogenicity after the first and second vaccination by use of electronic questionnaires on days 1, 3, 5, and 7. Immunogenicity was measured by the presence of SARS-CoV-2-specific antibodies (full spike-IgG, S1-IgG, and RBD-IgG), by an RBD-ACE2 binding inhibition assay (surrogate SARS-CoV-2 virus neutralisation test), a pseudovirus neutralisation assay against two variants of concerns (alpha [B.1.1.7] and beta [B.1.351]), and anti-S1-IgG avidity. T-cell reactivity was measured by IFN-γ release assay.FindingsBetween Dec 27, 2020, and June 14, 2021, 380 participants were enrolled in the study, with 174 receiving homologous BNT162b2 vaccination, 38 receiving homologous ChAdOx1 nCov-19 vaccination, and 104 receiving ChAdOx1 nCov-19-BNT162b2 vaccination. Systemic symptoms were reported by 103 (65%, 95% CI 57·1-71·8) of 159 recipients of homologous BNT162b2, 14 (39%, 24·8-55·1) of 36 recipients of homologous ChAdOx1 nCov-19, and 51 (49%, 39·6-58·5) of 104 recipients of ChAdOx1 nCov-19-BNT162b2 after the booster immunisation. Median anti-RBD IgG levels 3 weeks after boost immunisation were 5·4 signal to cutoff ratio (S/co; IQR 4·8-5·9) in recipients of homologous BNT162b2, 4·9 S/co (4·3-5·6) in recipients of homologous ChAdOx1 nCov-19, and 5·6 S/co (5·1-6·1) in recipients of ChAdOx1 nCov-19- BNT162b2. Geometric mean of 50% inhibitory dose against alpha and beta variants were highest in recipients of ChAdOx1 nCov-19-BNT162b2 (956·6, 95% CI 835·6-1095, against alpha and 417·1, 349·3-498·2, against beta) compared with those in recipients of homologous ChAdOx1 nCov-19 (212·5, 131·2-344·4, against alpha and 48·5, 28·4-82·8, against beta; both p<0·0001) or homologous BNT162b2 (369·2, 310·7-438·6, against alpha and 72·4, 60·5-86·5, against beta; both p<0·0001). SARS-CoV-2 S1 T-cell reactivity 3 weeks after boost immunisation was highest in recipients of ChAdOx1 nCov-19-BNT162b2 (median IFN-γ concentration 4762 mIU/mL, IQR 2723-8403) compared with that in recipients of homologous ChAdOx1 nCov-19 (1061 mIU/mL, 599-2274, p<0·0001) and homologous BNT162b2 (2026 mIU/mL, 1459-4621, p=0·0008) vaccination.InterpretationThe heterologous ChAdOx1 nCov-19-BNT162b2 immunisation with 10-12-week interval, recommended in Germany, is well tolerated and improves immunogenicity compared with homologous ChAdOx1 nCov-19 vaccination with 10-12-week interval and BNT162b2 vaccination with 3-week interval. Heterologous prime-boost immunisation strategies for COVID-19 might be generally applicable.FundingForschungsnetzwerk der Universitätsmedizin zu COVID-19, the German Ministry of Education and Research, Zalando SE.

Project description:Fractional dose is an important strategy to increase access to vaccines. This study evaluated the effectiveness, safety, and immunogenicity of half dose of ChAdOx1 nCoV-19 vaccine. A non-inferiority non-randomized controlled trial compared a half dose of ChAdOx1 nCoV-19 with the full dose, with an interval of 8 to 10 weeks, in individuals aged 18-49 years. The primary endpoints were the incidence rate of new cases/1,000 person-year at 90 days after 14 days of the second dose, confirmed by RT-PCR and new cases registered at SUS National Health Surveillance Database (e-SUS VS). The anti-SARS-CoV-2 spike (S) protein receptor binding domain (RBD) by chemiluminescence and the neutralizing antibodies by plaque reduction neutralization test (PRNT) were titrated. The soluble biomarkers were quantified with a multiplex immunoassay. Follow-up was 90 days after 14 days of the second dose. A total of 29,598 individuals were vaccinated. After exclusion, 16,570 individuals who received half a dose and 6,402 who received full doses were analyzed. The incidence of new cases confirmed by RT-PCR of half dose was non-inferior to full dose (23.7 vs. 25.7 cases per 1,000 persons-year [coefficient group -0.09 CI95%(-0.49 to 0.31)], even after adjusting for age and sex. There were no deaths or hospitalization after immunization of either group. Immunogenicity was evaluated in a subsample (N=558) compared to 154 healthcare workers who received a full dose. The seroconversion rate in seronegative individuals at baseline half dose was 99.8%, similar to that of the full dose (100%). Geometric mean concentration (95% CI; BAU/mL) were half dose = 188 (163-217) and full dose = 529 (423-663) (p < 0.001). In seropositive subjects at baseline (pre-immune individuals), the first dose induced very high and similar IgG-S in half dose 1,359 (1,245-1,483) and full dose 1,354 (1,048-1,749) BAU/mL. A half dose induced a high increase in plasma chemokines, pro-inflammatory/regulatory cytokines, and growth factors. The frequency of adverse events was similar. No serious adverse events or deaths were reported. A half dose of ChAdOx1 nCoV-19 is as effective, safe, and immunogenic as the full dose. The immune response in pre-immune (seropositive in the baseline) individuals indicates that the half dose may be a booster dose schedule.

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Immunogenicity and safety of an intradermal ChAdOx1 nCoV-19 boost in a healthy population.

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Immunogenicity and safety of an intradermal ChAdOx1 nCoV-19 boost in a healthy population.

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