Th1 skewed immune response of whole virion inactivated SARS CoV 2 vaccine and its safety evaluation.
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ABSTRACT:
SUBMITTER: Ganneru B
PROVIDER: S-EPMC7944858 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:This study followed healthcare personnel (HCP) who had completed a primary series of CoronaVac and then received the third and fourth doses of COVID-19 vaccine. The primary objective was to determine the seroconversion rate of neutralizing antibodies against wild-type SARS-CoV-2 and VOCs at day 28 after the third dose of vaccine and day 28 after the fourth dose of vaccine. This prospective cohort study was conducted at Maharaj Nakorn Chiang Mai Hospital, a tertiary care hospital affiliated to Chiang Mai University from July 2021 to February 2022. Two hundred and eighty-three participants were assessed for eligibility; 142 had received AZD1222 and 141 BNT162b2 as the third dose. Seroconversion rates using a 30% inhibition cutoff value against wild-type SARS-CoV-2 were 57.2%, 98.6%, 97.8%, and 98.9% at points before and after the third dose, before and after the fourth dose, respectively among those receiving AZD1222 as the third dose. Frequencies were 31.9%, 99.3%, 98.9%, and 100% among those receiving BNT162b2 as the third dose, respectively. The seroconversion rates against B.1.1.529 [Omicron] were 76.1% and 90.2% (p-value 0.010) at 4 weeks after the third dose in those receiving AZD1222 and BNT162b2 as the third dose, respectively. After a booster with the mRNA vaccine, the seroconversion rates increased from 21.7 to 91.3% and from 30.4 to 91.3% in those receiving AZD1222 and BNT162b2 as the third dose, respectively. No serious safety concerns were found in this study. In conclusion, antibody responses waned over time regardless of the vaccine regimen. The booster dose of the vaccine elicited a humoral immune response against SARS-CoV-2 including SARS-CoV-2 variants of concern, including B.1.1.529 [Omicron], which was circulating during the study period. However, the results might not be extrapolated to other Omicron sublineages.
| S-EPMC10643552 | biostudies-literature
Project description:The availability of a safe and effective vaccine would be the eventual measure to deal with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) threat. Here, we have assessed the immunogenicity and protective efficacy of inactivated SARS-CoV-2 vaccine candidates BBV152A, BBV152B, and BBV152C in Syrian hamsters. Three dose vaccination regimes with vaccine candidates induced significant titers of SARS-CoV-2-specific IgG and neutralizing antibodies. BBV152A and BBV152B vaccine candidates remarkably generated a quick and robust immune response. Post-SARS-CoV-2 infection, vaccinated hamsters did not show any histopathological changes in the lungs. The protection of the hamster was evident by the rapid clearance of the virus from lower respiratory tract, reduced virus load in upper respiratory tract, absence of lung pathology, and robust humoral immune response. These findings confirm the immunogenic potential of the vaccine candidates and further protection of hamsters challenged with SARS-CoV-2. Of the three candidates, BBV152A showed the better response.
| S-EPMC7829205 | biostudies-literature
Project description:BackgroundCoronaVac, an inactivated whole-virion SARS-CoV-2 vaccine, has been shown to be well tolerated with a good safety profile in individuals aged 18 years and older in phase 1/2 trials, and provided a good humoral response against SARS-CoV-2. We present the interim efficacy and safety results of a phase 3 clinical trial of CoronaVac in Turkey.MethodsThis was a double-blind, randomised, placebo-controlled phase 3 trial. Volunteers aged 18-59 years with no history of COVID-19 and with negative PCR and antibody test results for SARS-CoV-2 were enrolled at 24 centres in Turkey. Exclusion criteria included (but were not limited to) immunosuppressive therapy (including steroids) within the past 6 months, bleeding disorders, asplenia, and receipt of any blood products or immunoglobulins within the past 3 months. The K1 cohort consisted of health-care workers (randomised in a 1:1 ratio), and individuals other than health-care workers were also recruited into the K2 cohort (randomised in a 2:1 ratio) using an interactive web response system. The study vaccine was 3 μg inactivated SARS-CoV-2 virion adsorbed to aluminium hydroxide in a 0·5 mL aqueous suspension. Participants received either vaccine or placebo (consisting of all vaccine components except inactivated virus) intramuscularly on days 0 and 14. The primary efficacy outcome was the prevention of PCR-confirmed symptomatic COVID-19 at least 14 days after the second dose in the per protocol population. Safety analyses were done in the intention-to-treat population. This study is registered with ClinicalTrials.gov (NCT04582344) and is active but no longer recruiting.FindingsAmong 11 303 volunteers screened between Sept 14, 2020, and Jan 5, 2021, 10 218 were randomly allocated. After exclusion of four participants from the vaccine group because of protocol deviations, the intention-to-treat group consisted of 10 214 participants (6646 [65·1%] in the vaccine group and 3568 [34·9%] in the placebo group) and the per protocol group consisted of 10 029 participants (6559 [65·4%] and 3470 [34·6%]) who received two doses of vaccine or placebo. During a median follow-up period of 43 days (IQR 36-48), nine cases of PCR-confirmed symptomatic COVID-19 were reported in the vaccine group (31·7 cases [14·6-59·3] per 1000 person-years) and 32 cases were reported in the placebo group (192·3 cases [135·7-261·1] per 1000 person-years) 14 days or more after the second dose, yielding a vaccine efficacy of 83·5% (95% CI 65·4-92·1; p<0·0001). The frequencies of any adverse events were 1259 (18·9%) in the vaccine group and 603 (16·9%) in the placebo group (p=0·0108) with no fatalities or grade 4 adverse events. The most common systemic adverse event was fatigue (546 [8·2%] participants in the vaccine group and 248 [7·0%] the placebo group, p=0·0228). Injection-site pain was the most frequent local adverse event (157 [2·4%] in the vaccine group and 40 [1·1%] in the placebo group, p<0·0001).InterpretationCoronaVac has high efficacy against PCR-confirmed symptomatic COVID-19 with a good safety and tolerability profile.FundingTurkish Health Institutes Association.
| S-EPMC8266301 | biostudies-literature
Project description:This study evaluates the functional capacity of CD4+ and CD8+ terminally-differentiated effector (TEMRA), central memory (TCM), and effector memory (TEM) cells obtained from the volunteers vaccinated with an aluminum-adjuvanted inactivated whole-virion SARS-CoV-2 vaccine (CoronaVac). The volunteers were followed for T cell immune responses following the termination of a randomized phase III clinical trial. Seven days and four months after the second dose of the vaccine, the memory T cell subsets were collected and stimulated by autologous monocyte-derived dendritic cells (mDCs) loaded with SARS-CoV-2 spike glycoprotein S1. Compared to the placebo group, memory T cells from the vaccinated individuals significantly proliferated in response to S1-loaded mDCs. CD4+ and CD8+ memory T cell proliferation was detected in 86% and 78% of the vaccinated individuals, respectively. More than 73% (after a short-term) and 62% (after an intermediate-term) of the vaccinated individuals harbored TCM and/or TEM cells that responded to S1-loaded mDCs by secreting IFN-γ. The expression of CD25, CD38, 4-1BB, PD-1, and CD107a indicated a modulation in the memory T cell subsets. Especially on day 120, PD-1 was upregulated on CD4+ TEMRA and TCM, and on CD8+ TEM and TCM cells; accordingly, proliferation and IFN-γ secretion capacities tended to decline after 4 months. In conclusion, the combination of inactivated whole-virion particles with aluminum adjuvants possesses capacities to induce functional T cell responses.
| S-EPMC10028771 | biostudies-literature
Project description:BackgroundCurrent worldwide pandemic coronavirus disease 2019 (COVID-19) with high numbers of mortality rates and huge economic problems require an urgent demand for safe and effective vaccine development. Inactivated SARS-CoV2 vaccine with alum. Hydroxide can play an important role in reducing the impacts of the COVID-19 pandemic. In this study, vaccine efficacy was evaluated through the detection of the neutralizing antibodies that protect mice from challenge with SARS-CoV 2 3 weeks after the second dose. We conclude that the vaccine described here has safety and desirable properties, and our data support further development and plans for clinical trials.MethodsCharacterized SARS-COV-2 strain, severe acute respiratory syndrome coronavirus 2 isolates (SARS-CoV-2/human/EGY/Egy-SERVAC/2020) with accession numbers; MT981440; MT981439; MT981441; MT974071; MT974069; and MW250352 at GenBank were isolated from Egyptian patients SARS-CoV-2-positive. Development of inactivated vaccine was carried out in a BSL-3 facilities and the immunogenicity was determined in mice at two doses (55 and 100 μg per dose).ResultsThe distinct cytopathic effect induced by SARS-COV-2 propagation on Vero cell monolayers and the viral particles were identified as Coronaviridae by transmission electron microscopy and RT-PCR on infected cells cultures. Immunogenicity of the developed vaccine indicated the high antigen-binding and neutralizing antibody titers, regardless of the dose concentration, with excellent safety profiles and no deaths or clinical symptoms in mice groups. The efficacy of the inactivated vaccine formulation was tested by the wild virus challenge of the vaccinated mice and viral replication detection in lung tissues.ConclusionsVaccinated mice recorded complete protection from challenge infection via inhibition of SARS-COV-2 replication in the lung tissues of mice following virus challenge, regardless of the level of serum neutralizing antibodies. This finding will support future trials for the evaluation of an applicable SARS-CoV-2 vaccine candidate.
| S-EPMC8287638 | biostudies-literature
Project description:BackgroundDevelopment of safe and effective vaccine options is crucial to the success of fight against COVID-19 pandemic. Herein, we report interim safety and immunogenicity findings of the phase 1&2 trials of ERUCoV-VAC, an inactivated whole virion SARS-CoV-2 vaccine.MethodsDouble-blind, randomised, single centre, phase 1 and 2 trials included SARS-CoV-2 seronegative healthy adults aged 18-55 years (18-64 in phase 2). All participants, except the first 4 in phase 1 who received ERUCoV-VAC 3 μg or 6 μg unblinded and monitored for 7 days for safety purposes, were assigned to receive two intramuscular doses of ERUCoV-VAC 3 μg or 6 μg (an inactivated vaccine containing alhydrogel as adjuvant) or placebo 21 days apart (28 days in phase 2) according to computer-generated randomisation schemes. Both trials are registered at ClinicalTrials.gov (phase 1, NCT04691947 and phase 2, NCT04824391).ResultsForty-four participants (3 μg [n:17], 6 μg [n:17], placebo [n:10]) in phase 1 and 250 (3 μg [n:100], 6 μg [n:100], placebo [n:50]) in phase 2 received ≥1 dose. In phase 1 trial, 25 adverse events AEs (80 % mild) occured in 15 participants (34.1 %) until day 43. There was no dose-response relationship noted in safety events in ERUCoV-VAC recipients (p = 0.4905). Pain at injection site was the most common AE (9/44;20.5 %). Both doses of ERUCoV-VAC 3 μg and 6 μg groups were comparable in inducing SARS-CoV-2 wild-type neutralising antibody (MNT50): GMTs (95 %CI) were 8.3 (6.4-10.3) vs. 8.6 (7.0-10.2) at day 43 (p = 0.7357) and 9.7 (6.0-13.4) vs. 10.8 (8.8-12.8) at day 60 (p = 0.8644), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wild-type neutralising antibody GMTs (95 %CI) were 8.4 (6.3-10.5) vs. 9.0 (7.2-10.8) at day 43 (p = 0.5393) and 11.0 (7.0-14.9) vs. 12.3 (10.3-14.5) at day 60 (p = 0.8578). Neutralising antibody seroconversion rates (95 %CI) were 86.7 % (59.5-98.3) vs 94.1 % (71.3-99.8) at day 43 (p = 0.8727) and 92.8 % (66.1-99.8) vs. 100 % (79.4-100.0) at day 60 (p = 0.8873), in ERUCoV-VAC 3 μg and 6 μg groups, respectively. In phase 2 trial, 268 AEs, (67.2 % moderate in severity) occured in 153 (61.2 %) participants. The most common local and systemic AEs were pain at injection site (23 events in 21 [8.4 %] subjects) and headache (56 events in 47 [18.8 %] subjects), respectively. Pain at injection site was the only AE with a significantly higher frequency in the ERUCoV-VAC groups than in the placebo arm in the phase 2 study (p = 0.0322). ERUCoV-VAC groups were comparable in frequency of AEs (p = 0.4587). ERUCoV-VAC 3 μg and 6 μg groups were comparable neutralising antibody (MNT50): GMTs (95 %CI) were 30.0 (37.9-22.0) vs. 34.9 (47.6-22.1) at day 43 (p = 0.0666) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60, (p = 0.2166), respectively. FRNT50 confirmed MNT50 results: SARS-CoV-2 wildtype neutralising antibody GMTs were 28.9 (20.0-37.7) and 30.1 (18.5-41.6) at day 43 (p = 0.3366) and 34.2 (23.8-44.5) and 39.6 (22.7-58.0) at day 60 (p = 0.8777). Neutralising antibody seroconversion rates (95 %CI) were 95.7 % (91.4-99.8) vs. 98.9 % (96.9-100.0) at day 43 (p = 0.8710) and 96.6 % (92.8-100.0) vs 98.9 % (96.7-100.0) at day 60 (p = 0.9129) in ERUCoV-VAC 3 μg and 6 μg groups, respectively.ConclusionsTwo-dose regimens of ERUCoV-VAC 3 μg and 6 μg 28 days both had an acceptable safety and tolerability profile and elicited comparable neutralising antibody responses and seroconversion rates exceeding 95 % at day 43 and 60 after the first vaccination. Data availability Data will be made available on request.
| S-EPMC9678819 | biostudies-literature
Project description:Since the emergence of SARS-CoV-2 at the end of 2019, 64 candidate vaccines are in clinical development and 173 are in the pre-clinical phase. Five types of vaccines are currently approved for emergency use in many countries (Inactivated, Sinopharm; Viral-vector, Astrazeneca, and Gamaleya Research Institute; mRNA, Moderna, and BioNTech/Pfizer). The main challenge in this pandemic was the availability to produce an effective vaccine to be distributed to the world's population in a short time. Herein, we developed a whole virus NRC-VACC-01 inactivated candidate SARS-CoV-2 vaccine and tested its safety and immunogenicity in laboratory animals. In the preclinical studies, we used four experimental animals (mice, rats, guinea pigs, and hamsters). Antibodies were detected as of week three post vaccination and continued up to week ten in the four experimental models. Safety evaluation of NRC-VACC-01 inactivated candidate vaccine in rats revealed that the vaccine was highly tolerable. By studying the effect of booster dose in the immunological profile of vaccinated mice, we observed an increase in neutralizing antibody titers after the booster shot, thus a booster dose was highly recommended after week three or four. Challenge infection of hamsters showed that the vaccinated group had lower morbidity and shedding than the control group. A phase I clinical trial will be performed to assess safety in human subjects.
| S-EPMC7999656 | biostudies-literature
Project description:Data science has been an invaluable part of the COVID-19 pandemic response with multiple applications, ranging from tracking viral evolution to understanding the vaccine effectiveness. Asymptomatic breakthrough infections have been a major problem in assessing vaccine effectiveness in populations globally. Serological discrimination of vaccine response from infection has so far been limited to Spike protein vaccines since whole virion vaccines generate antibodies against all the viral proteins. Here, we show how a statistical and machine learning (ML) based approach can be used to discriminate between SARS-CoV-2 infection and immune response to an inactivated whole virion vaccine (BBV152, Covaxin). For this, we assessed serial data on antibodies against Spike and Nucleocapsid antigens, along with age, sex, number of doses taken, and days since last dose, for 1823 Covaxin recipients. An ensemble ML model, incorporating a consensus clustering approach alongside the support vector machine model, was built on 1063 samples where reliable qualifying data existed, and then applied to the entire dataset. Of 1448 self-reported negative subjects, our ensemble ML model classified 724 to be infected. For method validation, we determined the relative ability of a random subset of samples to neutralize Delta versus wild-type strain using a surrogate neutralization assay. We worked on the premise that antibodies generated by a whole virion vaccine would neutralize wild type more efficiently than delta strain. In 100 of 156 samples, where ML prediction differed from self-reported uninfected status, neutralization against Delta strain was more effective, indicating infection. We found 71.8% subjects predicted to be infected during the surge, which is concordant with the percentage of sequences classified as Delta (75.6%-80.2%) over the same period. Our approach will help in real-world vaccine effectiveness assessments where whole virion vaccines are commonly used.
| S-EPMC9040372 | biostudies-literature
Project description:ImportanceA surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021.ObjectiveTo assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection.Design, setting, and participantsThis was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India.ExposuresVaccination with 0, 1, or 2 doses of BBV152.Main outcomes and measuresThe HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported.ResultsAmong 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection.Conclusions and relevanceThese findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.
| S-EPMC8742193 | biostudies-literature
Project description:Enterovirus 71 (EV71) has caused epidemics of hand, foot and mouth diseases in Asia during the past decades and no vaccine is available. A formalin-inactivated EV71 candidate vaccine (EV71vac) based on B4 subgenotype has previously been developed and found to elicit strong neutralizing antibody responses in mice and humans. In this study, we evaluated the long-term immunogenicity and safety of this EV71vac in a non-human primate model. Juvenile macaques were immunized at 0, 3 and 6 weeks either with 10 or 5 µg doses of EV71vac formulated with AlPO4 adjuvant, or PBS as control. During the 56 weeks of studies, no fever nor local redness and swelling at sites of injections was observed in the immunized macaques. After single immunization, 100% seroconversion based on 4-fold increased in neutralization titer (Nt) was detected in EV71vac immunized monkeys but not PBS controls. A dose-dependent IgG antibody response was observed in monkeys receiving EV71vac immunization. The Nt of EV71vac immunized macaques had reached the peak after 3 vaccinations, then decreased gradually; however, the GMT of neutralizing antibody in the EV71vac immunized macaques were still above 100 at the end of the study. Correspondingly, both dose- and time-dependent interferon-? and CD4+ T cell responses were detected in monkeys receiving EV71vac. Interestingly, similar to human responses, the dominant T cell epitopes of macaques were identified mainly in VP2 and VP3 regions. In addition, strong cross-neutralizing antibodies against most EV71 subgenotypes except some C2 and C4b strains, and Coxsackievirus A16 were observed. In summary, our results indicate that EV71vac elicits dose-dependent T-cell and antibody responses in macaques that could be a good animal model for evaluating the long-term immune responses elicited by EV71 vaccines.
| S-EPMC4157806 | biostudies-literature