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Background: Inactivated whole-virus vaccination elicits immune responses to both SARS-CoV-2 nucleocapsid (N) and spike (S) proteins, like natural infections. A heterologous Ad26.COV2.S booster given at two different intervals after primary BBIBP-CorV vaccination was safe and immunogenic at days 28 and 84, with higher immune responses observed after the longer pre-boost interval. We describe booster-specific and hybrid immune responses over 1 year., Methods: This open-label phase 1/2 study was conducted in healthy Thai adults aged ≥ 18 years who had completed primary BBIBP-CorV primary vaccination between 90-240 (Arm A1; n = 361) or 45-75 days (Arm A2; n = 104) before enrolment. All received an Ad26.COV2.S booster. We measured anti-S and anti-N IgG antibodies by Elecsys®, neutralizing antibodies by SARS-CoV-2 pseudovirus neutralization assay, and T-cell responses by quantitative interferon (IFN)-γ release assay. Immune responses were evaluated in the baseline-seronegative population (pre-booster anti-N < 1.4 U/mL; n = 241) that included the booster-effect subgroup (anti-N < 1.4 U/mL at each visit) and the hybrid-immunity subgroup (anti-N ≥ 1.4 U/mL and/or SARS-CoV-2 infection, irrespective of receiving non-study COVID-19 boosters)., Results: In Arm A1 of the booster-effect subgroup, anti-S GMCs were 131-fold higher than baseline at day 336; neutralizing responses against ancestral SARS-CoV-2 were 5-fold higher than baseline at day 168; 4-fold against Omicron BA.2 at day 84. IFN-γ remained approximately 4-fold higher than baseline at days 168 and 336 in 18-59-year-olds. Booster-specific responses trended lower in Arm A2. In the hybrid-immunity subgroup at day 336, anti-S GMCs in A1 were 517-fold higher than baseline; neutralizing responses against ancestral SARS-CoV-2 and Omicron BA.2 were 28- and 31-fold higher, respectively, and IFN-γ was approximately 14-fold higher in 18-59-year-olds at day 336. Durable immune responses trended lower in ≥ 60-year-olds., Conclusion: A heterologous Ad26.COV2.S booster after primary BBIBP-CorV vaccination induced booster-specific immune responses detectable up to 1 year that were higher in participants with hybrid immunity., Clinical Trials Registration: NCT05109559., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.M., R.W., S.K., S.L., A.J., A.T., V.L., P.C., N.T., N.C. report no potential conflicts of interest. S.N. has received honoraria for lectures from GSK, Zuellig Pharma, Astra Zeneca, Novartis, Abbot, Sanofi, Organon and Takeda and has participated in advisory boards for GlaxoSmithKline and Takeda. J.K.L. and T.A.W. and received institutional funding from Mahidol University to support study conduct, and T.A.W. supported management of Data Safety Monitoring Board activities and meetings. J-L.E. has no competing interests to declare.. M.F.R. is an employee of Janssen Pharmaceuticals and holds restricted stock units in the company. C.L. is an employee of Janssen Pharmaceuticals. T.K.M. has received consulting fees from Janssen Pharmaceuticals. P.P. has received funding from Mahidol University and Johnson & Johnson for study support., (Copyright © 2024. Published by Elsevier Ltd.)

The surge in coronavirus disease 2019 (COVID-19) caused by the Omicron variants of the severe acute respiratory syndrome coronavirus 2 necessitates researches to inform vaccine effectiveness (VE) and other preventive measures to halt the pandemic. A test-negative case-control study was conducted among adults (age ≥18 years) who were at-risk for COVID-19 and presented for nasopharyngeal real-time polymerase chain reaction testing during the Omicron variant-dominant period in Thailand (1 January 2022-15 June 2022). All participants were prospectively followed up for COVID-19 development for 14 days after the enrolment. Vaccine effectiveness was estimated and adjusted for characteristics associated with COVID-19. Of the 7971 included individuals, there were 3104 cases and 4867 controls. The adjusted VE among persons receiving 2-dose, 3-dose, and 4-dose vaccine regimens for preventing infection and preventing moderate-to-critical diseases were 33%, 48%, 62% and 60%, 74%, 76%, respectively. The VE were generally higher among those receiving the last dose of vaccine within 90 days compared to those receiving the last dose more than 90 days prior to the enrolment. The highest VE were observed in individuals receiving the 4-dose regimen, CoronaVac-CoronaVac-ChAdOx1 nCoV-19-BNT162b2 for both preventing infection (65%) and preventing moderate-to-critical diseases (82%). Our study demonstrated increased VE along with an increase in number of vaccine doses received. Current vaccination programmes should focus on reducing COVID-19 severity and mandate at least one booster dose. The heterologous boosters with viral vector and mRNA vaccines were highly effective and can be used in individuals who previously received the primary series of inactivated vaccine.

Objective: To evaluate immunogenicity and safety of heterologous COVID-19 primary vaccination regimens of CoronaVac with fractional and standard BNT162b2 dosages in 5-11-year-old Thai children., Methods: This prospective, multicenter, double-blind, randomized control trial divided participants 1:1:1:1 to receive a second dose of either standard (10-μg) or half-dose (5-μg) BNT162b2 vaccines as follows: CoronaVac/10-μg-BNT162b2 (Group 1), CoronaVac/5-μg-BNT162b2 (Group 2), 10-μg-BNT162b2/10-μg-BNT162b2 (Group 3), or 10-μg-BNT162b2/5-μg-BNT162b2 (Group 4). A subset of participants from each arm received 10-μg-BNT162b2 booster (third) doses 16 weeks after their second vaccination. Humoral and cellular immunogenicity were assessed and adverse events (AEs) digitally self-reported., Results: Of 553 enrolled participants, 50 % were male, the median (interquartile range) age was 8.65 (7.00, 10.00) years, and a majority (91 %) had normal weight-for-height. All participants exhibited similarly robust neutralizing antibodies (NAb) against the ancestral Wuhan strain two weeks after the second vaccination, with titers highest in Group 1 (737.60, 95% CI [654.80, 830.88]), followed by Groups 3 (630.42, 95% CI [555.50, 715.45]), 2 (593.98, 95% CI [506.02, 697.23]), and 4 (451.79, 95% CI [388.62, 525.23]), as well as 56.01 % and 49.68 % seroconversion for BA.1 and BA.5, respectively. Half-dose BNT162b2 as a second dose induced significantly lower NAb titers compared to their respective full-dose regimens (p = 0.03 for Groups 1 vs 2 and p < 0.001 for Groups 3 vs 4). 77.71 % of participants developed SARS-CoV-2 ancestral spike protein-specific T-cell responses two weeks after the second vaccination. This was similar across arms. Booster doses generated NAb titers 5.69-11.51-folds higher than the second vaccination against BA.1. AEs were similar across arms, all mild or moderate, and fully resolved 2-3 days thereafter., Conclusion: Standard and fractional heterologous regimens of CoronaVac-BNT162b2 induced similar or higher humoral immunity than homologous BNT162b2 and represent alternative vaccine regimens for children. These findings are highly relevant in settings concurrently using both vaccines., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: The inactivated COVID-19 whole-virus vaccine BBIBP-CorV has been extensively used worldwide. Heterologous boosting after primary vaccination can induce higher immune responses against SARS-CoV-2 than homologous boosting. The safety and immunogenicity after 28 days of a single Ad26.COV2.S booster dose given at different intervals after 2 doses of BBIBP-CorV are presented., Methods: This open-label phase 1/2 trial was conducted in healthy adults in Thailand who had completed 2-dose primary vaccination with BBIBP-CorV. Participants received a single booster dose of Ad26.COV2.S (5 × 10 10 virus particles) 90-240 days (Group A1; n = 360) or 45-75 days (Group A2; n = 66) after the second BBIBP-CorV dose. Safety and immunogenicity were assessed over 28 days. Binding IgG antibodies to the full-length pre-fusion Spike and anti-nucleocapsid proteins of SARS-CoV-2 were measured by enzyme-linked immunosorbent assay. The SARS-CoV-2 pseudovirus neutralization assay and live virus microneutralization assay were used to quantify the neutralizing activity of antibodies against ancestral SARS-CoV-2 (Wuhan-Hu-1) and the delta (B.1.617.2) and omicron (B.1.1.529/BA.1 and BA.2) variants. The cell-mediated immune response was measured using a quantitative interferon (IFN)-γ release assay in whole blood., Results: Solicited local and systemic adverse events (AEs) on days 0-7 were mostly mild, as were unsolicited vaccine-related AEs during days 0-28, with no serious AEs. On day 28, anti-Spike binding antibodies increased from baseline by 487- and 146-fold in Groups A1 and A2, and neutralizing antibodies against ancestral SARS-CoV-2 by 55- and 37-fold, respectively. Humoral responses were strongest against ancestral SARS-CoV-2, followed by the delta, then the omicron BA.2 and BA.1 variants. T-cell-produced interferon-γ increased approximately 10-fold in both groups., Conclusions: A single heterologous Ad26.COV2.S booster dose after two BBIBP-CorV doses was well tolerated and induced robust humoral and cell-mediated immune responses measured at day 28 in both interval groups., Clinical Trials Registration: NCT05109559., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.M., R.W., S.K., S.L., A.J., A.T., V.L., P.C., N.T., N.C. report no potential conflicts of interest. S.N. has received honoraria for lectures from GSK, Zuellig Pharma, Astra Zeneca, Novartis, Abbot, Sanofi, Organon and Takeda and has participated in advisory boards for GlaxoSmithKline and Takeda. J.K.L. and T.A.W. and received institutional funding from Mahidol University to support study conduct, and T.A.W. supported management of Data Safety Monitoring Board activities and meetings. J-L.E. has received funding from Mahidol University and Johnson & Johnson for study support, and is the coordinator of the study Data Safety Monitoring Board. M.F.R. is an employee of Janssen Pharmaceuticals and holds restricted stock units in the company. C.L. is an employee of Janssen Pharmaceuticals. T.K.M. has received consulting fees from Janssen Pharmaceuticals. P.P. has received funding from Mahidol University and Johnson & Johnson for study support., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The study aimed to compare the immunogenicity and safety of fractional (half) third doses of heterologous COVID-19 vaccines (AZD1222 or BNT162b2) to full doses after the two-dose CoronaVac and when boosting after three different extended intervals., Methods: At 60-<90, 90-<120, or 120-180 days intervals after the two-dose CoronaVac, participants were randomized to full-dose or half-dose AZD1222 or BNT162b2, followed up at day 28, 60, and 90. Vaccination-induced immune responses to Ancestral, Delta, and Omicron BA.1 strains were evaluated by antispike, pseudovirus, and microneutralization and T cell assays. Descriptive statistics and noninferiority cut-offs were reported as geometric mean concentration or titer and concentration or titer ratios comparing baseline to day 28 and day 90 and different intervals., Results: No safety concerns were detected. All assays and intervals showed noninferior immunogenicity between full doses and half doses. However, full-dose vaccines and/or longer 120-180-day intervals substantially improved the immunogenicity (measured by antispike or measured by pseudotyped virus neutralizing titers 50; P <0.001). Seroconversion rates were over 90% against the SARS-CoV-2 strains by all assays. Immunogenicity waned more quickly with half doses than full doses but remained high against the Ancestral or Delta strains. Against Omicron, the day 28 immunogenicity increased with longer intervals than shorter intervals for full-dose vaccines., Conclusion: Immune responses after day 28 when boosting at longer intervals after the two-dose CoronaVac was optimal. Half doses met the noninferiority criteria compared with the full dose by all the immune assays assessed., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Data on real-life vaccine effectiveness (VE), against the delta variant (B.1.617.2) of the severe acute respiratory syndrome coronavirus 2 among various coronavirus disease 2019 (COVID-19) vaccine regimens are urgently needed to impede the COVID-19 pandemic. We conducted a test-negative case-control study to assess the VE of various vaccine regimens for preventing COVID-19 during the period when the delta variant was the dominant causative virus (≥ 95%) in Thailand (25 July 2021-23 Oct 2021). All individuals (age ≥18 years) at-risk for COVID-19, presented for nasopharyngeal real-time polymerase chain reaction (RT-PCR) testing, were prospectively enrolled and followed up for disease development. Vaccine effectiveness was estimated with adjustment for individual demographic and clinical characteristics. Of 3353 included individuals, there were 1118 cases and 2235 controls. The adjusted VE among persons receiving two-dose CoronaVac plus one BNT162b2 booster was highest (98%; 95% confidence interval [CI] 87-100), followed by those receiving two-dose CoronaVac plus one ChAdOx1 nCoV-19 booster (86%; 95% CI 74-93), two-dose ChAdOx1 nCoV-19 (83%; 95% CI 70-90), one CoronaVac dose and one ChAdOx1 nCoV-19 dose (74%; 95% CI 43-88) and two-dose CoronaVac (60%; 95% CI 49-69). One dose of CoronaVac or ChAdOx1 nCoV-19 had a VE of less than 50%. Our study demonstrated the incremental VE with the increase in the number of vaccine doses received. The two-dose CoronaVac plus one BNT162b2 or ChAdOx1 nCoV-19 booster regimens was highly effective in preventing COVID-19 during the rise of delta variant.

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, 5x10 10 viral particles) or low dose (LD, 2.5x10 10 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., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Ltd.)

Wannada Laisuan,1 Chamard Wongsa,2 Chirawat Chiewchalermsri,3 Torpong Thongngarm,2 Ticha Rerkpattanapipat,1 Pansa Iamrahong,4 Chulapha Ruangwattanachok,4 Sira Nanthapisal,5 Mongkhon Sompornrattanaphan2 1Division of Allergy, Immunology and Rheumatology, Department of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 2Division of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; 3Department of Medicine, Panyananthaphikkhu Chonprathan Medical Center, Srinakharinwirot University, Nonthaburi, Thailand; 4Clinical Pharmacy Section, Pharmacy Division, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand; 5Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, ThailandCorrespondence: Mongkhon SompornrattanaphanDivision of Allergy and Clinical Immunology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, ThailandTel +66 2419 8263Fax +66 2419 8263Email mongkhon.som@mahidol.ac.thAbstract: Anaphylaxis to CoronaVac, an inactivated vaccine against COVID-19, is extremely rare. We report 12 cases of anaphylaxis after CoronaVac administration, focusing on clinical characteristics and management outcomes. Skin test and graded vaccine challenge were successfully performed in our cases and might be considered if an inactivated vaccine is the only remaining option.Keywords: anaphylaxis, COVID-19 vaccine, drug allergy, excipient, vaccine allergy, COVID-19, skin testing