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1.
International Journal of Infectious Diseases ; 2022.
Article in English | ScienceDirect | ID: covidwho-2004135

ABSTRACT

Introduction : Older adults are subject to higher COVID-19 infection and mortality rates. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine have been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age, however, older adults were under-represented. Methods : A double-blind, randomized, multi-center study compared safety and immunogenicity of high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart in 420 participants of 65 years and older. The results have been stratified by the comorbidity status. Results : Both high and mid-dose regimens elicited mostly mild adverse events and robust immune responses when measured as neutralizing and binding antibodies titers. High doses elicited better immune responses in the group without comorbidities. Conclusion : Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommend high dose for immunization of elder adults with MVC-COV1901. The clinical trial was registered at https://clinicaltrials.gov/ (NCT04822025).

2.
Emerg Microbes Infect ; 11(1): 1664-1671, 2022 Dec.
Article in English | MEDLINE | ID: covidwho-1978179

ABSTRACT

To reach the WHO target of hepatitis C virus (HCV) elimination by 2025, Taiwan started to implement free-of-charge direct-acting antiviral (DAA) treatment programme in 2017. Evaluating the progress of HCV microelimination among people living with HIV (PLWH) is a critical step to identify the barriers to HCV elimination. PLWH seeking care at a major hospital designated for HIV care in Taiwan between January 2011 and December 2021 were retrospectively included. For PLWH with HCV-seropositive or HCV seroconversion during the study period, serial HCV RNA testing was performed using archived samples to confirm the presence of HCV viremia and estimate the prevalence and incidence of HCV viremia. Overall, 4199 PLWH contributed to a total of 27,258.75 person-years of follow-up (PYFU). With the reimbursement of DAAs and improvement of access to treatments, the prevalence of HCV viremia has declined from its peak of 6.21% (95% CI, 5.39-7.12%) in 2018 to 2.09% (95% CI, 1.60-2.77%) in 2021 (decline by 66.4% [95% CI, 55.4-74.7%]); the incidence has declined from 25.94 per 1000 PYFU (95% CI, 20.44-32.47) in 2019 to 12.15% per 1000 PYFU (95% CI, 8.14-17.44) (decline by 53.2% [95% CI, 27.3-70.6%]). However, the proportion of HCV reinfections continued to increase and accounted for 82.8% of incident HCV infections in 2021. We observed significant declines of HCV viremia among PLWH with the expansion of the DAA treatment programme in Taiwan. Further improvement of the access to DAA retreatments is warranted to achieve the goal of HCV microelimination.


Subject(s)
HIV Infections , Hepatitis C, Chronic , Hepatitis C , Antiviral Agents/therapeutic use , HIV Infections/drug therapy , HIV Infections/epidemiology , Hepacivirus/genetics , Hepatitis C/drug therapy , Hepatitis C/epidemiology , Hepatitis C, Chronic/drug therapy , Humans , Retrospective Studies , Taiwan/epidemiology , Viremia/drug therapy , Viremia/epidemiology
3.
Infect Dis Ther ; 11(4): 1493-1504, 2022 Aug.
Article in English | MEDLINE | ID: covidwho-1850469

ABSTRACT

INTRODUCTION: MVC-COV1901 is a protein subunit COVID-19 vaccine based on the stable prefusion spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide. Interim results of a phase 2 clinical trial demonstrated favorable safety profile and immunogenicity and the vaccine has been authorized for use in Taiwan. However, waning antibody levels after immunization and variants of concern (VoC) could negatively impact vaccine-induced neutralization of virus. In this extension to the phase 1 clinical study we investigated a three-dose regimen of MVC-COV1901 for durability of antibody levels and virus neutralization capacity, including neutralization of the Omicron variant. METHODS: Forty-five healthy adults from 20 to 49 years of age were divided into three groups of 15 participants receiving two doses of either low dose (LD), medium dose (MD), or high dose (HD) of MVC-COV1901. Six months after the second dose (day 209), a third MD dose of MVC-COV1901 was administered to the LD and MD groups and a HD dose was given to the HD group. Safety was followed for up to 28 days after the booster dose by monitoring incidences of adverse events (AE). Immunogenicity and antibody persistence for up to 6 months after the booster dose were assessed by neutralizing assay with the wild-type (Wuhan) SARS-CoV-2 virus. To examine the immunogenicity of booster dose against variants, neutralizing assays were carried out with the Alpha, Beta, and Delta variant viruses and the Omicron variant pseudovirus using samples from 4 weeks after the booster dose. RESULTS: Adverse reactions after the booster dose were mostly mild and comparable to that of the first two doses. Compared to day 209, neutralizing antibodies were increased by 10.3-28.9 times at 4 weeks after the booster. During the 6-month follow-up after the booster, the rate of decline of neutralizing antibody level was much less than that after the second dose. Three doses of MVC-COV1901 also improved antibody-mediated neutralization of Alpha, Beta, and Delta variants as well as the Omicron variant pseudovirus. CONCLUSION: Our data showed increased persistence of neutralizing antibodies and enhancement of immunogenicity against VoCs offered after a third dose of MVC-COV1901. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT04487210.

4.
J Microbiol Immunol Infect ; 55(3): 535-539, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1819544

ABSTRACT

COVID-19 vaccination is recommended for at-risk populations, but the vaccine effectiveness in people living with HIV (PLWH) remains incompletely understood. Here we demonstrate that COVID-19 vaccination was clinically effective among PLWH during the outbreak setting with a low endemicity of COVID-19 where non-pharmaceutical interventions were strictly implemented.


Subject(s)
COVID-19 , HIV Infections , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines , Disease Outbreaks/prevention & control , HIV Infections/complications , HIV Infections/epidemiology , Humans , Vaccination
5.
Lancet Respir Med ; 9(12): 1396-1406, 2021 12.
Article in English | MEDLINE | ID: covidwho-1621134

ABSTRACT

BACKGROUND: MVC-COV1901, a recombinant protein vaccine containing pre-fusion-stabilised spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide, has been shown to be well tolerated with a good safety profile in healthy adults aged 20-49 years in a phase 1 trial, and provided a good cellular and humoral immune responses. We present the interim safety, tolerability, and immunogenicity results of a phase 2 clinical trial of the MVC-COV1901 vaccine in Taiwan. METHODS: This is a large-scale, double-blind, randomised, placebo-controlled phase 2 trial done at ten medical centres and one regional hospital in Taiwan. Individuals aged 20 years or older who were generally healthy or had stable pre-existing medical conditions were eligible for enrolment. Exclusion criteria included (but were not limited to) travel overseas within 14 days of screening, intention to travel overseas within 6 months of the screening visit, and the absence of prespecified medical conditions, including immunosuppressive illness, a history of autoimmune disease, malignancy with risk to recur, a bleeding disorder, uncontrolled HIV infection, uncontrolled hepatitis B and C virus infections, SARS-CoV-1 or SARS-CoV-2 infections, an allergy to any vaccine, or a serious medical condition that could interfere with the study. Study participants were randomly assigned (6:1) to receive two doses of either MVC-COV1901 or placebo, administered via intramuscular injection on day 1 and day 29. MVC-COV1901 contained 15 µg of S-2P protein adjuvanted with 750 µg CpG 1018 and 375 µg aluminium hydroxide in a 0·5 mL aqueous solution, and the placebo contained the same volume of saline. Randomisation was done centrally by use of an interactive web response system, stratified by age (≥20 to <65 years and ≥65 years). Participants and investigators were masked to group assignment. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from day 1 (the day of the first dose) to day 57 (28 days after the second dose). Safety was assessed in all participants who received at least one dose. Immunogenicity was assessed by measuring geometric mean titres (GMTs) and seroconversion rates of neutralising antibody and antigen-specific IgG in the per-protocol population. This study is registered with ClinicalTrials.gov, NCT04695652. FINDINGS: Of 4173 individuals screened between Dec 30, 2020, and April 2, 2021, 3854 were enrolled and randomly assigned: 3304 to the MVC-COV1901 group and 550 to the placebo group. A total of 3844 participants (3295 in the MVC-COV1901 group and 549 in the placebo group) were included in the safety analysis set, and 1053 participants (903 and 150) had received both doses and were included in the per-protocol immunogenicity analysis set. From the start of this phase 2 trial to the time of interim analysis, no vaccine-related serious adverse events were recorded. The most common solicited adverse events in all study participants were pain at the injection site (2346 [71·2%] of 3295 in the MVC-COV1901 group and 128 [23·3%] of 549 in the placebo group), and malaise or fatigue (1186 [36·0%] and 163 [29·7%]). Fever was rarely reported (23 [0·7%] and two [0·4%]). At 28 days after the second dose of MVC-COV1901, the wild-type SARS-CoV-2 neutralising antibody GMT was 662·3 (95% CI 628·7-697·8; 408·5 IU/mL), the GMT ratio (geometric mean fold increase in titres at day 57 vs baseline) was 163·2 (155·0-171·9), and the seroconversion rate was 99·8% (95% CI 99·2-100·0). INTERPRETATION: MVC-COV1901 has a good safety profile and elicits promising immunogenicity responses. These data support MVC-COV1901 to enter phase 3 efficacy trials. FUNDING: Medigen Vaccine Biologics and Taiwan Centres for Disease Control, Ministry of Health and Welfare.


Subject(s)
Adjuvants, Immunologic , Aluminum Hydroxide , COVID-19 Vaccines/immunology , COVID-19 , HIV Infections , Oligodeoxyribonucleotides , Adult , Aged , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Double-Blind Method , Humans , Middle Aged , SARS-CoV-2 , Taiwan , Young Adult
6.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-296594

ABSTRACT

Objectives To provide data on the immune response to COVID-19 vaccines in people living with HIV (PWH), MVC-COV1901, a recombinant protein vaccine containing S-2P protein adjuvanted with CpG 1018 and aluminium hydroxide, was assessed. Methods A total of 57 PWH of ≥ 20 years of age who are on stable antiretroviral therapy and with CD4 + T cell ≥ 350 cells/mm 3 and HIV viral load < 10 3 copies/ml were compared with 882 HIV-negative participants. Participants received 2 doses of MVC-COV1901 28 days apart. Safety and the immunogenicity were evaluated. Results No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in people living with HIV (PWH) and comparators, respectively, 28 days after second dose. The geometric mean titers (GMTs) (95% confidence interval [CI]) against wild type SARS-CoV-2 virus were 136.62 IU/mL (WHO Standardized International Unit) (95% CI 114.3-163.3) and 440.41 IU/mL (95% CI 421.3-460.4), for PWH and control groups, respectively, after adjusting for sex, age, BMI category, and comorbidity, and the adjusted GMT ratio of comparator/PWH was 3.22 (95% CI 2.6-4.1). A higher CD4/CD8 ratio was associated with a higher GMT (R=0.27, p=0.039). Conclusions MVC-COV1901 has shown robust safety but weaker immunogenicity responses in PWH. As a result, a third dose or booster doses of MVC-COV1901 may be appropriate for PWH.

7.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-294956

ABSTRACT

Abstract: In this extension of the phase 1 clinical study, we report the immunogenicity and reactogenicity of the booster dose of a COVID-19 vaccine, MVC-COV1901, administered six months after the completion of the primary two dose schedule. Antibody persistence was detected at 6 months after the second dose of MVC-COV1901, albeit at reduced levels. At 28 days after the booster dose, the neutralizing antibody titer was 1.7-fold higher compared to the previous peak at 2 weeks after the second dose. These data demonstrated the safety and immunogenicity of booster shot of MVC-COV1901 after the primary schedule of the vaccine.

8.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-293592

ABSTRACT

Abstract: In this extension of the phase 1 clinical study, we report the immunogenicity and reactogenicity of the booster dose of a COVID-19 vaccine, MVC-COV1901, administered six months after the completion of the primary two dose schedule. Antibody persistence was detected at 6 months after the second dose of MVC-COV1901, albeit at reduced levels. At 28 days after the booster dose, the neutralizing antibody titer was 1.7-fold higher compared to the previous peak at 2 weeks after the second dose. These data demonstrated the safety and immunogenicity of booster shot of MVC-COV1901 after the primary schedule of the vaccine.

9.
EClinicalMedicine ; 38: 100989, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1375926

ABSTRACT

BACKGROUND: This was a phase 1, dose-escalation open-label trial to evaluate the safety and immunogenicity of MVC-COV1901, a SARS-CoV-2 S-2P protein vaccine adjuvanted with aluminum hydroxide and CpG 1018. METHODS: Between September 28 and November 13 2020, 77 participants were screened. Of these, 45 healthy adults from 20 to 49 years of age were to be administered two doses of MVC-COV1901 in doses of 5 µg, 15 µg, or 25 µg of spike protein at 28 days apart. There were 15 participants in each dose group; all were followed for 28 days after the second dose at the time of the interim analysis. Adverse events and laboratory data were recorded for the safety evaluation. Blood samples were collected for humoral, and cellular immune response at various time points. Trial Registration: ClinicalTrials.gov NCT04487210. FINDINGS: Solicited adverse events were mostly mild and similar. No subject experienced fever. After the second dose, the geometric mean titers (GMTs) for SARS-CoV-2 spike-specific immunoglobulin G were 7178.2, 7746.1, 11,220.6 in the 5 µg, 15 µg, and 25 µg dose groups, respectively. The neutralizing activity were detected in both methods. (Day 43 GMTs, 538.5, 993.1, and 1905.8 for pseudovirus; and 33.3, 76.3, and 167.4 for wild-type virus). The cellular immune response induced by MVC-COV1901 demonstrated substantially higher numbers of IFN-γ- producing cells, suggesting a Th1-skewed immune response. INTERPRETATION: The MVC-COV1901 vaccine was well tolerated and elicited robust immune responses and is suitable for further development. FUNDING: Medigen Vaccine Biologics Corporation.

10.
Microorganisms ; 9(6)2021 Jun 15.
Article in English | MEDLINE | ID: covidwho-1270088

ABSTRACT

Studies had shown that severe cases of COVID-19 tend to have high viral loads and correlate with functional impairment of cytotoxic lymphocytes, and the features of cytokine storm syndrome are similar to manifestations of severe influenza that have been partially explained by suppressed perforin expression. To test the hypothesis that the spike glycoprotein from SARS-CoV-2 may inhibit the perforin expression, we determined the kinetics of immune responses of CD8+ T cells to low dose (LD) or high dose (HD) of S1 stimulation through an in vitro dendritic cell (DC)-T cell model over seven days of incubation. The cytotoxic activity and intracellular perforin expression of CD8+ T cells induced by HD-S1-presenting DCs were aberrantly lower than those induced by LD-S1-presenting DCs from day three of incubation. Discrepantly, the levels of lymphoproliferation and cytokine (interferon-γ and tumor necrosis factor-α) production induced by HD-S1-presenting DCs were significantly higher than those induced by LD-S1-presenting DCs from day four. The dose-related responses between doses of S1 and intracellular perforin expression showed a significant linear correlation with a negative slope. In conclusion, the S1 subunit may suppress the perforin expression in CD8+ T cells to decrease the cytotoxic capacity to kill spike-presenting cells in a dose-dependent manner; the persistence of antigen presentation may result in an overproduction of interferon-γ and subsequent proinflammatory cytokines. That may help explain the insufficient cytotoxicity against high quantities of viruses or highly replicated strains of SARS-CoV-2 in severe cases of COVID-19.

11.
J Formos Med Assoc ; 120(12): 2186-2190, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1198883

ABSTRACT

We presented the clinical course and immune responses of a well-controlled HIV-positive patient with COVID-19. The clinical presentation and antibody production to SARS-CoV-2 were similar to other COVID-19 patients without HIV infection. Neutralizing antibody reached a plateau from 26th to 47th day onset but decreased on 157th day after symptoms.


Subject(s)
COVID-19 , HIV Infections , Antibodies, Neutralizing , Antibodies, Viral , Enzyme-Linked Immunosorbent Assay , HIV Infections/complications , Humans , Immunoglobulin G , SARS-CoV-2
13.
J Formos Med Assoc ; 120(7): 1459-1463, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1014623

ABSTRACT

BACKGROUND: Healthcare workers (HCWs) are at the frontline during the pandemic of COVID-19 globally. According to the WHO situation report at April 17, there were 22, 073 HCWs contracted the infection. Whether the infection control policy and practice in the hospital setting can protect the HCWs is an important issue. METHODS: We performed a cross-sectional serology study in a tertiary care hospital in Taiwan to explore the sero-prevalence rate among HCWs. The participants are enrolled on a voluntary basis. A structured questionnaire was collected to gather the epidemiology character and risk factors for potential exposure. ELISA tests as Architect SARS-CoV-2 IgG (Abbott) and Elecsys Anti-SARS-CoV-2 assay (Roche) were used to detect antibody responses. If any of the tests was positive, a western blot assay was used for confirmation. RESULTS: There were 194 HCWs participated during July 1 to Aug. 31, 2020. The mean age was 36.3 ± 10.4. More than half of the participants had possible hospital associated risk for COVID-19 exposure (110/192, 57.3%) and 64 had possible community risk for COVID-19 exposure (64/194, 33.0%). There was only one participant had positive test by Architect IgG test and confirmed to be negative for seasonal coronavirus and SARS-CoV-2 antibody. (Mikrogen Diagnostik, Germany). CONCLUSION: The cross-sectional serology study in a tertiary care hospital in Taiwan revealed no HCWs had positive serology response to SARS-CoV-2. We believe that the infection control policy and practice in the hospital and in the community are both important to prevent the disease transmission.


Subject(s)
COVID-19 , Health Personnel , Adult , COVID-19/epidemiology , Cross-Sectional Studies , Hospitals , Humans , Middle Aged , Seroepidemiologic Studies , Taiwan/epidemiology
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