Immunogenicity and reactogenicity of mRNA COVID-19 vaccine booster administered by intradermal or intramuscular route in Thai older adults (preprint)

Introduction: Intradermal (ID) vaccination may alleviate COVID-19 vaccine shortages and vaccine hesitancy due to systemic reactogenicity among older adults. Objectives: To compare the immunogenicity and reactogenicity of fractional ID and standard intramuscular (IM) booster vaccination of mRNA-1273 and BNT162b2 vaccines in older adults. Methods: Participants aged [≥]65 years who previously vaccinated with 2-dose ChAdOx1 were randomized to receive one of the four booster vaccinations: 0.1mL ID mRNA-1273, 0.5mL IM mRNA-1273, 0.1mL ID BNT162b2 and 0.3mL IM BNT162b2. Immunogenicity as measured by anti-receptor binding domain (anti-RBD) IgG against Wuhan, neutralising antibody (NAb) against Wuhan and Omicron BA.1, BA.2 and BA.4/5, and IFN{gamma}-producing cells. Local and systemic adverse effects (AEs) were self-reported via an electronic diary card. Results: Of the 210 participants enrolled, 70.5% were female and median age was 77.5 years (interquartile range (IQR): 71.0-84.0). Following the booster dose, both ID vaccination induced 37% lower levels of anti-RBD IgG than IM vaccination of the same vaccine. NAb against ancestral and Omicron BA.1 strains was highest following IM mRNA-1273 (1,718 and 617), followed by ID mRNA-1273 (1,212 and 318), IM BNT162b2 (713 and 230), and ID BNT162b2 (587 and 148), respectively. Spike-specific IFN{gamma} responses were similar or higher in the ID groups when compared with their respective IM groups. Vaccine delivery through ID route tended to have lower systemic AEs, although more local AEs reported in ID mRNA-1273 group. Conclusions: Fractional ID vaccination induced immunogenicity and reactogenicity comparable to IM and may be an alternative option for older people.

Safety and Immunogenicity of Intradermal Administration of Fractional Dose CoronaVac(R), ChAdOx1 nCoV-19 and BNT162b2 as Primary Series Vaccination (preprint)

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, 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. The FRNT50 titers were lowest against the omicron variant, being undetectable (GMT[≤]10) 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 generates similar immune responses with tendency of lower systemic adverse reactions than intramuscular vaccination. Our findings have implications in settings where COVID-19 vaccines are in shortage.

Immunogenicity and reactogenicity against the SARS-CoV-2 variants following heterologous primary series involving CoronaVac and ChAdOx1 and BNT162b2 plus heterologous BNT162b2 booster vaccination: An open-label randomized study in healthy Thai adults. (preprint)

We evaluated the immunogenicity and reactogenicity of heterologous COVID-19 primary series vaccination schedules. Participants were randomized to one of seven groups that received two-dose homologous BNT162b2 or heterologous combinations of CoronaVac, ChAdOx1 and BNT162b2, with 4 weeks interval. Of 210 participants, median age was 38 (19-60) years, 51% were female. The groups that received BNT162b2 as second dose induced the highest virus-specific IgG response against the ancestral strain [BNT162b2: geometric mean concentration (GMC) 2133-2249, 95%CI 1558 to 3055; ChAdOx1: 851-1201, 95%CI 649 to 1522; CoronaVac: 137-225, 95%CI 103-286 BAU/mL], neutralising antibodies (NAb) against Beta and Delta, and interferon gamma response. All groups induced low to negligible NAb against Omicron. A BNT162b2 booster (3rd dose) following heterologous CoronaVac and ChAdOx1 regimens induced >140-fold increase in NAb titres against Omicron. Our findings indicate that heterologous regimens using BNT162b2 as the second dose may be considered an alternative schedule to maximize immune response.