Homologous and Heterologous Boosting of the Chadox1-S1-S COVID-19 Vaccine With the SCB-2019 Vaccine Candidate: A Randomized, Controlled, Phase 2 Study.

Background: Ongoing outbreaks of coronavirus disease 2019 (COVID-19) are driven by waning immunity following primary immunizations and emergence of new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants that escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity. Methods: We assessed the immunogenicity and reactogenicity of booster doses of different formulations of aluminium hydroxide-adjuvanted SCB-2019 vaccine (9 µg of SCB-2019, with or without CpG-1018 adjuvant, or 30 µg of SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by enzyme-linked immunosorbent assay (ELISA) on days 1, 15, and 29. Participants self-reported solicited adverse events and reactions. Results: All SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 µg of SCB-2019 + CpG + aluminium hydroxide, titers against wild-type S-protein were significantly higher than after ChAdOx1-S on days 15 and 29, as were titers of neutralizing antibodies against the wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated, with no vaccine-related serious or severe adverse events. Conclusions: Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, with the highest responses being with the 30-µg SCB-2019 + CpG + aluminium hydroxide formulation. Clinical Trials Registration: NCT05087368.

Immunogenicity of an adjuvanted SARS-CoV-2 trimeric S-protein subunit vaccine (SCB-2019) in SARS-CoV-2-naïve and exposed individuals in a phase 2/3, double-blind, randomized study.

BACKGROUND: We evaluated immunogenicity of SCB-2019, a subunit vaccine candidate containing a pre-fusion trimeric form of the SARS-CoV-2 spike (S)-protein adjuvanted with CpG-1018/alum. METHODS: The phase 2/3, double-blind, randomized SPECTRA trial was conducted in five countries in participants aged ≥ 18 years, either SARS-CoV-2-naïve or previously exposed. Participants were randomly assigned to receive two doses of SCB-2019 or placebo administered intramuscularly 21 days apart. In the phase 2 part of the study, on days 1, 22, and 36, neutralizing antibodies were measured by pseudovirus and wild-type virus neutralization assays to SARS-CoV-2 prototype and variants, and ACE2-receptor-binding antibodies and SCB-2019-binding antibodies were measured by ELISA. Cell-mediated immunity was measured by intracellular cytokine staining via flow cytometry. RESULTS: 1601 individuals were enrolled between 24 March and 13 September 2021 and received at least one vaccine dose. Immunogenicity analysis was conducted in a phase 2 subset of 691 participants, including 428 SARS-CoV-2-naïve (381 vaccine and 47 placebo recipients) and 263 SARS-CoV-2-exposed (235 vaccine and 28 placebo recipients). In SARS-CoV-2-naïve participants, GMTs of neutralizing antibodies against prototype virus increased 2 weeks post-second dose (day 36) compared to baseline (224 vs 12.7 IU/mL). Seroconversion rate was 82.5 %. In SARS-CoV-2-exposed participants, one SCB-2019 dose increased GMT of neutralizing antibodies by 48.3-fold (1276.1 IU/mL on day 22) compared to baseline. Seroconversion rate was 92.4 %. Increase was marginal post-second dose. SCB-2019 also showed cross-neutralization capability against nine variants, including Omicron, in SARS-CoV-2-exposed participants at day 36. SCB-2019 stimulated Th1-biased cell-mediated immunity to the S-protein in both naïve and exposed participants. The vaccine was well tolerated, no safety concerns were raised from the study. CONCLUSIONS: A single dose of SCB-2019 was immunogenic in SARS-CoV-2-exposed individuals, whereas two doses were required to induce immune response in SARS-CoV-2-naïve individuals. SCB-2019 elicited a cross-neutralizing response against emergent SARS-CoV-2 variants at antibody levels associated with clinical protection, underlining its potential as a booster. CLINICALTRIALS: gov: NCT04672395; EudraCT: 2020-004272-17.

Homologous and heterologous boosting of the ChAdOx1-S1-S COVID-19 vaccine with the SCB-2019 vaccine candidate: a randomized, controlled, phase 2 study

Background Ongoing outbreaks of COVID-19 are driven by waning immunity following primary immunizations and emergence of new SARS-CoV-2 variants which escape vaccine-induced neutralizing antibodies. It has been suggested that heterologous boosters could enhance and potentially maintain population immunity. Methods We assessed immunogenicity and reactogenicity of booster doses of different formulations of aluminium hydroxide-adjuvanted SCB-2019 vaccine (9 μg SCB-2019 with or without CpG-1018 adjuvant, or 30 μg SCB-2019 with CpG-1018) in Brazilian adults primed with ChAdOx1-S vector vaccine. S-protein antibodies and ACE2-binding inhibition were measured by ELISA on Days 1, 15 and 29. Participants self-reported solicited adverse events and reactions. Results All SCB-2019 formulations increased S-protein ELISA antibodies and ACE2 binding inhibition to a greater extent than ChAdOx1-S. After 30 μg SCB-2019 + CpG + aluminium hydroxide titers against wild-type S-protein were significantly higher than after ChAdOx1-S on Days 15 and 29, as were titers of neutralizing antibodies against wild-type strain and Beta, Gamma, Delta, and Omicron variants. Boosting with SCB-2019 or ChAdOx1-S was well tolerated with no vaccine-related serious or severe adverse events. Conclusions Boosting ChAdOx1-S-primed adults with SCB-2019 induced higher levels of antibodies against a wild-type strain and SARS-CoV-2 variants than a homologous ChAdOx1-S booster, highest responses being with the 30 μg SCB-2019 + CpG + aluminium hydroxide formulation.

Evaluation of the exposure risk of SARS-CoV-2 in different hospital environment.

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant impact on social and economic activities. As a high infectious pathogen, the existence of SARS-CoV-2 in public space is very important for its transmission. During the COVID-19 pandemic, hospitals are the main places to deal with the diseases. In this work, we evaluated the exposure risk of SARS-CoV-2 in hospital environment in order to protect healthcare workers (HCWs). Briefly, air and surface samples from 6 different sites of 3 hospitals with different protection levels were collected and tested for the SARS-CoV-2 nucleic acid by reverse transcription real-time fluorescence PCR method during the COVID-19 epidemic. We found that the positive rate of SARS-CoV-2 nucleic acid was 7.7 % in a COVID-19 respiratory investigation wards and 82.6 % in a ICUs with confirmed COVID-19 patients. These results indicated that in some wards of the hospital, such as ICUs occupied by COVID-19 patients, the nucleic acid of SARS-CoV-2 existed in the air and surface, which indicates the potential occupational exposure risk of HCWs. This study has clarified retention of SARS-CoV-2 in different sites of hospital, suggesting that it is necessary to monitor and disinfect the SARS-CoV-2 in hospital environment during COVID-19 pandemic, and will help to prevent the iatrogenic infection and nosocomial transmission of SARS-CoV-2 and to better protect the HCWs.