Immunogenicity of a Fractional Dose of mRNA BNT162b2 COVID-19 Vaccine for Primary Series and Booster Vaccination among Healthy Adolescents.

Primary series vaccination with BNT162b2 followed by a booster 5 months later has been recommended for healthy adolescents. We aimed to describe the immunogenicity in a fractional dose of BNT162b2. Adolescents aged 12-18 years were randomized into six arms for primary series administration: 3wPZ30/30 (reference group), 3wPZ30/20, 3wPZ20/20, 6wPZ30/30, 6wPZ30/20, and 6wPZ20/20 µg. A booster was given at 5 months after the second dose using either 10 or 15 µg of BNT162b2. Immunogenicity following vaccination was determined by IgG against receptor-binding domain (anti-S-RBD IgG; BAU/mL), surrogate virus neutralization test (sVNT; %inhibition) and pseudovirus neutralization (pVNT;ID50) against Omicron. Non-inferiority criteria were defined as a lower boundary of the geometric mean ratio (GMR) being greater than 0.67. From September to October 2021, 118 adolescents with a median age (IQR) of 14.9 years (13.9-16.7) were enrolled. Fourteen days after the primary series, the geometric means (GMs) of anti-S-RBD IgG (BAU/mL) were 3090 (95% CI 2761-3460) in 3wPZ30/30. The GMRs of anti-S-RBD were: 0.80 (95% CI 0.67-0.97) in 3wPZ30/20; 1.00 (95% CI 0.83-1.20) in 3wPZ20/20; 1.37 (95% CI 1.13-1.65) in 6wPZ30/30; 1.24 (95% CI 1.02-1.50) in 6wPZ30/20; and 1.36 (1.13-1.64) in 6wPZ20/20. After a booster dose with 15 µg (n = 24) of BNT162b2, sVNT and pVNT against Omicron variant were 91.6 (95% CI 88.4-94.9) and 331 (95% CI 221-495), respectively. In the group that received 10 µg of BNT162b2 (n = 25), sVNT was 85.6 (95% CI 80.0-91.6) and pVNT was 397 (95% CI 267-590). Healthy adolescents had good immune responses to the fractional dose regimen of BNT162b2 and this may be considered as an alternative option.

Heterologous Prime-boost of SARS-CoV-2 inactivated vaccine and mRNA BNT162b2 among Healthy Thai Adolescents.

Background: Heterologous prime-boost SARS-CoV-2 vaccination is a widely accepted strategy during the COVID-19 pandemic, which generated a superior immune response than homologous vaccination strategy. Objective: To describe immunogenicity of heterologous prime-boost vaccination with inactivated vaccine, CoronaVac, followed by BNT162b2 and 5-month booster dose with BNT162b2 in healthy Thai adolescents. Methods: Adolescents aged 12-18 years were randomized 1:1:1:1 to receive CoronaVac (SV) followed by BNT162b2 (PZ) 30 or 20 µg at either 3- or 6-week interval (SV3w/PZ30µg, SV3w/PZ20µg, SV6w/PZ30µg or SV6w/PZ20µg). During the Omicron-predominant period, participants were offered a BNT162b2 booster dose 30, 15, or 10 µg. Immunogenicity was determined using IgG antibody against spike-receptor-binding domain of wild type(anti-S-RBD IgG) and surrogate virus neutralization test(sVNT) against Delta variant at 14 days and 5 months after the 2nd dose. Neutralization tests(sVNT and pseudovirus neutralization test; pVNT) against Omicron strain were tested pre- and 14 days post-booster dose. Results: In October 2021, 76 adolescents with a median age of 14.3 years (IQR 12.7-16.0) were enrolled: 20 in SV3w/PZ30µg; 17 in SV3w/PZ20µg; 20 in SV6w/PZ30µg; 19 in SV6w/PZ20µg. At day 14, the geometric mean(GM) of anti-S-RBD IgG in SV3w/PZ30µg was 4713 (95 %CI 4127-5382) binding-antibody unit (BAU)/ml, while geometric mean ratio(GMR) was 1.28 (1.09-1.51) in SV6w/PZ30µg. The GMs of sVNT against Delta variants at day 14 among participants in SV3w/PZ30µg and SV6wk/PZ30µg arm were 95.3 % and 99.7 %inhibition, respectively. At 5 months, GMs of sVNT against Delta variants in SV3w/PZ30µg were significantly declined to 47.8 % but remained at 89.0 % inhibition among SV6w/PZ30µg arm. In April 2022, 52 adolescents received a BNT162b2 booster dose. Proportion of participants with sVNT against Omicron strain > 80 %inhibition was significantly increased from 3.8 % pre-booster to 67 % post-booster. Proportion of participants with pVNT ID50 > 185 was 42 % at 14 days post 2nd dose and 88 % post booster, respectively. Conclusions: Heterologous prime-boost vaccination with CoronaVac followed by BNT162b2 induced high neutralizing titer against SARS-CoV-2 Delta strain. After 5-month interval, booster with BNT162b2 induced high neutralizing titer against Omicron strain.Thai Clinical Trials Registry (thaiclinicaltrials.org): TCTR20210923012.

A Randomized Clinical Trial of a Fractional Low Dose of BNT162b2 Booster in Adults Following AZD1222.

In the era of globally predominant omicron strains, a COVID-19 booster vaccine is needed. Our study aimed to evaluate the immunogenicity of a half-dose BNT162b2 booster after AZD1222 in healthy adults. A randomized trial of volunteers aged 18-69 years who received two-dose AZD1222 was conducted. The participants were randomized to receive the BNT162b2 vaccine intramuscularly-half (15 µg) vs. standard dose (30 µg). The immunogenicity was evaluated by a surrogate virus neutralization test (sVNT) against omicron variants and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG). From November-December 2021, 100 adults with a median age of 59.3 years (IQR 33.4-65.5) were enrolled. A booster dose was given at median of 98 days (IQR 92-128) after AZD1222. At day 14, the geometric means (GMs) of anti-S-RBD IgG in half- vs. standard-dose group were 2329.8 vs. 2574.7 BAU/mL, with a geometric mean ratio (GMR) of 0.90 (0.77-1.06). The GMs of sVNT against the omicron variant in the half- and standard-dose groups were 74.4% inhibition (95% CI 68.8-80.5) and 67.3% inhibition (57.9-78.1), respectively, with GMR of 0.95 (0.69-1.30). At day 90, the sVNT indicated 22.3% inhibition (95% CI 14.9-33.4) and 20.4% inhibition (13.1-32.0), respectively, with GMR of 1.09 (0.60-1.98). The fractional low-dose BNT162b2 mRNA booster vaccine provided non-inferior immunogenicity responses. During a shortage of vaccine supply, a fractional low dose should be considered for a booster vaccination program.

Immunogenicity and reactogenicity after booster dose with AZD1222 via intradermal route among adult who had received CoronaVac.

BACKGROUND: Currently, booster dose is needed after 2 doses of non-live COVID-19 vaccine. With limited resources and shortage of COVID-19 vaccines, intradermal(ID) administration might be a potential dose-sparing strategy. OBJECTIVE: To determine immunologic response and reactogenicity of ID ChAdOx1 nCoV-19 vaccine (AZD1222,Oxford/AstraZeneca) as a booster dose after completion of 2-dose CoronaVac(SV) in healthy adult. METHODS: This is a prospective cohort study of adult aged 18-59 years who received 2-dose SV at 14-35 days apart for more than 2 months. Participants received ID AZD1222 at fractional low dose(1×1010 viral particles,0.1 ml). Antibody responses were evaluated by surrogate virus neutralization test(sVNT) against delta variant and wild type, and anti-spike-receptor-binding-domain immunoglobulin G(anti-S-RBD IgG) at prior, day14, 28, 90, and 180 post booster. Solicited reactogenicity was collected for 7 days post-booster. Primary endpoint was the differences of sVNT against delta strain ≥ 80% inhibition at day14 and 90 compared with the parallel cohort study of 0.5-ml intramuscular(IM) route. RESULTS: From August2021, 100 adults with median age of 46 years(IQR 41-52) participated. Prior to booster, geometric mean(GM) of sVNT against delta strain was 22.4% inhibition(95 %CI 18.7-26.9) and of anti-S-RBD IgG was 109.3 BAU/ml(95.4-125.1). Post ID booster, GMs of sVNT against delta strain were 95.5% inhibition (95%CI 94.2-96.8) at day14, 73.1% inhibition (66.7-80.2) at day90, and 22.7% inhibition (14.9-34.6) at day180. The differences of proportion of participants achieving sVNT against delta strain ≥ 80% inhibition in ID recipients versus IM were + 4.2% (95 %CI -2.0to10.5) at day14, and -37.3%(-54.2to-20.3) at day90. Anti-S-RBD IgG GMs were 2037.1 BAU/ml (95%CI 1770.9-2343.2) at day14 and 744.6 BAU/ml(650.1-852.9) at day90, respectively. Geometric mean ratios(GMRs) of anti-S-RBD IgG were 0.99(0.83-1.20) at day14, and 0.82(0.66-1.02) at day90. Only 18% reported feverish, compared with 37% of IM (p = 0.003). Common reactogenicity was erythema at injection site(53%) while 7% reported blister. CONCLUSION: Low-dose ID AZD1222 booster enhanced lower neutralizing antibodies at 3 months compared with IM route. Less systemic reactogenicity occurred, but higher local reactogenicity.

A randomized clinical trial of a booster dose with low versus standard dose of AZD1222 in adult after 2 doses of inactivated vaccines.

BACKGROUND: Immunogenicity of inactivated SARS-CoV-2 vaccine has waning antibody over time. With the emergence of the SARS-CoV-2 delta variant, which requires higher neutralizing antibody to prevent infection, a booster dose is needed. OBJECTIVE: To evaluate immunogenicity and reactogenicity of standard- versus low-dose ChAdOx1 nCoV-19 vaccine booster after CoronaVac in healthy adults. METHODS: A double-blinded, randomized, controlled trial of adult, aged 18-59 years, with completion of 2-dose CoronaVac at 21-28 days apart for more than 2 months was conducted. Participants were randomized to receive AZD1222 (Oxford/AstraZeneca) intramuscularly; standard dose (SD, 5x1010 viral particles) or low dose (LD, 2.5x1010 viral particles). Surrogate virus neutralization test (sVNT) against wild type and delta variant, and anti-spike-receptor-binding-domain IgG (anti-S-RBD IgG) were compared as geometric mean ratio (GMR) at day 14 and 90 between LD and SD arms. RESULTS: From July-August 2021, 422 adults with median age of 44 (IQR 36-51) years were enrolled. The median interval from CoronaVac to AZD1222 booster was 77 (IQR 64-95) days. At baseline, geometric means (GMs) of sVNT against delta variant and anti-S-RBD IgG were 18.1%inhibition (95% CI 16.4-20.0) and 111.5 (105.1-118.3) BAU/ml. GMs of sVNT against delta variant and anti-S-RBD IgG in SD were 95.6%inhibition (95% CI 94.3-97.0) and 1975.1 (1841.7-2118.2) BAU/ml at day 14, and 89.4%inhibition (86.4-92.4) and 938.6 (859.9-1024.4) BAU/ml at day 90, respectively. GMRs of sVNT against delta variant and anti-S-RBD IgG in LD compared to SD were 1.00 (95% CI 0.98-1.02) and 0.84 (0.76-0.93) at day 14, and 0.98 (0.94-1.03) and 0.89 (0.79-1.00) at day 90, respectively. LD recipients had significantly lower rate of fever (6.8% vs 25.0%) and myalgia (51.9% vs 70.7%) compared to SD. CONCLUSION: Half-dose AZD1222 booster after 2-dose inactivated SARS-CoV-2 vaccination had non-inferior immunogenicity, yet lower systemic reactogenicity. Fractional low-dose AZD1222 booster should be considered especially in resource-constrained settings.