Humoral and cellular response induced by a second booster of an inactivated SARS-CoV-2 vaccine in adults

The SARS-CoV-2 Omicron variant has challenged the control of the COVID-19 pandemic even in highly vaccinated countries. While a second booster of mRNA vaccines improved the immunity against SARS-CoV-2, the humoral and cellular responses induced by a second booster of an inactivated SARS-CoV-2 vaccine have not been studied. In the context of a phase 3 clinical study, we report that a second booster of CoronaVac(R) increased the neutralizing response against the ancestral virus yet showed poor neutralization against the Omicron variant. Additionally, isolated PBMCs displayed equivalent activation of specific CD4+ T cells and IFN-{gamma} production when stimulated with a mega-pool of peptides derived from the spike protein of the ancestral virus or the Omicron variant. In conclusion, a second booster dose of CoronaVac(R) does not improve the neutralizing response against the Omicron variant compared with the first booster dose, yet it helps maintaining a robust spike-specific CD4+ T cell response.

Differential immune response induced by two immunization schedules with an inactivated SARS-CoV-2 vaccine in a randomized phase 3 clinical trial

BackgroundThe development of vaccines to control the COVID-19 pandemic progression is a worldwide priority. CoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved for emergency use with robust efficacy and immunogenicity data reported in trials in China, Brazil, Indonesia, Turkey, and Chile. MethodsThis study is a randomized, multicenter, and controlled phase 3 trial in healthy Chilean adults aged [≥]18 years. Volunteers received two doses of CoronaVac(R) separated by two (0-14 schedule) or four weeks (0-28 schedule). 2,302 volunteers were enrolled, 440 were part of the immunogenicity arm, and blood samples were obtained at different times. Samples from a single center are reported. Humoral immune responses were evaluated by measuring the neutralizing capacities of circulating antibodies. Cellular immune responses were assessed by ELISPOT and flow cytometry. Correlation matrixes were performed to evaluate correlations in the data measured. ResultsBoth schedules exhibited robust neutralizing capacities with the response induced by the 0-28 schedule being better. No differences were found in the concentration of antibodies against the virus and different variants of concern between schedules. Stimulation of PBMCs with MPs induced the secretion of IFN-{gamma} and the expression of activation induced markers for both schedules. Correlation matrixes showed strong correlations between neutralizing antibodies and IFN-{gamma} secretion. ConclusionsImmunization with CoronaVac(R) in Chilean adults promotes robust cellular and humoral immune responses. The 0-28 schedule induced a stronger humoral immune response than the 0-14 schedule. FundingMinistry of Health, Government of Chile, Confederation of Production and Commerce & Millennium Institute on Immunology and Immunotherapy, Chile. Clinical trial numberNCT04651790. summaryTwo immunization schedules were evaluated for the inactivated SARS-CoV-2 vaccine, Coronavac(R), with two doses of the vaccine separated by two or four weeks. We compared humoral and cellular immune responses, showing they are mostly similar, with differences in neutralization capacities.

A booster dose of an inactivated vaccine increases neutralizing antibodies and T cell responses against SARS-CoV-2

BackgroundCoronaVac(R) is an inactivated SARS-CoV-2 vaccine approved by the World Health Organization. Previous studies reported increased levels of neutralizing antibodies and specific T cells two- and four-weeks after two doses of CoronaVac(R), but the levels of neutralizing antibodies are reduced at six to eight months after two doses. Here we report the effect of a booster dose of CoronaVac(R) on the anti-SARS-CoV-2 immune response generated against variants of concern (VOC) Delta and Omicron in adults participating in a phase 3 clinical trial in Chile. MethodsVolunteers immunized with two doses of CoronaVac(R) in a four-week interval received a booster dose of the same vaccine between twenty-four and thirty weeks after the 2nd dose. Four weeks after the booster dose, neutralizing antibodies and T cell responses were measured. Neutralization capacities and T cell activation against VOC Delta and Omicron were detected at four weeks after the booster dose. FindingsWe observed a significant increase in neutralizing antibodies at four weeks after the booster dose. We also observed an increase in CD4+ T cells numbers over time, reaching a peak at four weeks after the booster dose. Furthermore, neutralizing antibodies and SARS-CoV-2 specific T cells induced by the booster showed activity against VOC Delta and Omicron. InterpretationOur results show that a booster dose of CoronaVac(R) increases the anti-SARS-CoV-2 humoral and cellular immune responses in adults. Immunity induced by a booster dose of CoronaVac(R) is active against VOC, suggesting an effective protection.

Interim Report: Safety And Immunogenicity Of An Inactivated Vaccine Against Sars-Cov-2 In Healthy Chilean Adults In A Phase 3 Clinical Trial

BackgroundThe ongoing COVID-19 pandemic has had a significant impact worldwide, with an incommensurable social and economic burden. The rapid development of safe and protective vaccines against this disease is a global priority. CoronaVac is a vaccine prototype based on inactivated SARS-CoV-2, which has shown promising safety and immunogenicity profiles in pre-clinical studies and phase 1/2 trials in China. To this day, four phase 3 clinical trials are ongoing with CoronaVac in Brazil, Indonesia, Turkey, and Chile. This article reports the safety and immunogenicity results obtained in a subgroup of participants aged 18 years and older enrolled in the phase 3 Clinical Trial held in Chile. MethodsThis is a multicenter phase 3 clinical trial. Healthcare workers aged 18 years and older were randomly assigned to receive two doses of CoronaVac or placebo separated by two weeks (0-14). We report preliminary safety results obtained for a subset of 434 participants, and antibody and cell-mediated immunity results obtained in a subset of participants assigned to the immunogenicity arm. The primary and secondary aims of the study include the evaluation of safety parameters and immunogenicity against SARS-CoV-2 after immunization, respectively. This trial is registered at clinicaltrials.gov (NCT04651790). FindingsThe recruitment of participants occurred between November 27th, 2020, until January 9th, 2021. 434 participants were enrolled, 397 were 18-59 years old, and 37 were [≥]60 years old. Of these, 270 were immunized with CoronaVac, and the remaining 164 participants were inoculated with the corresponding placebo. The primary adverse reaction was pain at the injection site, with a higher incidence in the vaccine arm (55.6%) than in the placebo arm (40.0%). Moreover, the incidence of pain at the injection site in the 18-59 years old group was 58.4% as compared to 32.0% in the [≥]60 years old group. The seroconversion rate for specific anti-S1-RBD IgG was 47.8% for the 18-59 years old group 14 days post immunization (p.i.) and 95.6% 28 and 42 days p.i. For the [≥]60 years old group, the seroconversion rate was 18.1%, 100%, and 87.5% at 14, 28, and 42 days p.i., respectively. Importantly, we observed a 95.7% seroconversion rate in neutralizing antibodies for the 18-59 years old group 28 and 42 days p.i. The [≥]60 years old group exhibited seroconversion rates of 90.0% and 100% at 28 and 42 days p.i. Interestingly, we did not observe a significant seroconversion rate of anti-N-SARS-CoV-2 IgG for the 18-59 years old group. For the participants [≥]60 years old, a modest rate of seroconversion at 42 days p.i. was observed (37.5%). We observed a significant induction of a T cell response characterized by the secretion of IFN-{gamma} upon stimulation with Mega Pools of peptides derived from SARS-CoV-2 proteins. No significant differences between the two age groups were observed for cell-mediated immunity. InterpretationImmunization with CoronaVac in a 0-14 schedule in adults of 18 years and older in the Chilean population is safe and induces specific IgG production against the S1-RBD with neutralizing capacity, as well as the activation of T cells secreting IFN-{gamma}, upon recognition of SARS-CoV-2 antigens. FundingMinistry of Health of the Chilean Government; Confederation of Production and Commerce, Chile; Consortium of Universities for Vaccines and Therapies against COVID-19, Chile; Millennium Institute on Immunology and Immunotherapy.

Analysis of Curative Effect of Posterior Cervical Pedicle Screw Fixation Operation for Cervical Spondylotic Myelopathy / 沈阳医学院学报

Objective:To evaluate the clinical effect of posterior cervical pedicle screw fixation operation for cervical spondylotic myelopathy.Methods: From Mar 2014 to Sep 2015, 55 patients with cervical spondylotic myelopathy treated with posterior cervical pedicle screw fixation operation were involved. Cervical curvature in the cervical three dimensional CT by the Harrison’ s cervical curvature measuring method was measured, and JOA scores, NDI scores and VAS scores before and after operation and the last follow-up were evaluated. Results:A total of 55 patients with cervical spondylotic myelopathy obtained good operation effect and the cervical curvature and neural function were improved.The cervical curvature, JOA score, NDI scores, and VAS scores were significantly better than that before operation (P < 0.05) . Last follow-up results showed that there was statistical significance on JOA score, NDI score, and VAS score compared with that after operation (P<0.05), but not on cervical curvature (P>0.05) . Conclusion:The neurological function and cervical curvature of the cervical spondylotic myelopathy can be improved through posterior cervical pedicle screw fixation operation.