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1.
Expert Rev Vaccines ; : 1-16, 2022 Nov 11.
Article in English | MEDLINE | ID: covidwho-2097134

ABSTRACT

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. However, the emergence of the Omicron variant and subvariants as the globally dominant strains have raised doubts about the effectiveness of currently available vaccines and prompted debate about potential future vaccination strategies. AREAS COVERED: Using the publicly available IVAC VIEW-hub platform, we reviewed 52 studies on vaccine effectiveness (VE) after booster vaccinations. VE were reported for SARS-CoV-2 symptomatic infection, severe disease and death and stratified by vaccine schedule and age. In addition, a non-systematic literature review of safety was performed to identify single or multi-country studies investigating adverse event rates for at least two of the currently available COVID-19 vaccines. EXPERT OPINION: Booster shots of the current COVID-19 vaccines provide consistently high protection against Omicron-related severe disease and death. Additionally, this protection appears to be conserved for at least 3 months, with a small but significant waning after that. The positive risk-benefit ratio of these vaccines is well established, giving us confidence to administer additional doses as required. Future vaccination strategies will likely include a combination of schedules based on risk profile, as overly frequent boosting may be neither beneficial nor sustainable for the general population.

3.
Expert Rev Vaccines ; 21(9): 1255-1268, 2022 09.
Article in English | MEDLINE | ID: covidwho-1908600

ABSTRACT

INTRODUCTION: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. While primary series vaccination rates are generally high in Southeast Asian (SEA) countries, various factors have limited the rollout and impact of booster doses. AREAS COVERED: We reviewed 79 studies in the International Vaccine Access Center (IVAC) VIEW-hub platform on vaccine effectiveness (VE) after primary immunizations with two-dose schedules. VE data were reported for SARS-CoV-2 infection, COVID-19-related hospitalizations and deaths, and stratified across variants of concern, age, study design and prior SARS-CoV-2 infection for mRNA vaccines (BNT162b2, mRNA-1273, and combinations of both), vector vaccines (AstraZeneca, AZD1222 [ChAdOx1 nCoV-19] 'Vaxzevria'), and inactivated virus vaccines (CoronaVac). EXPERT OPINION: The most-studied COVID-19 vaccines provide consistently high (>90%) protection against serious clinical outcomes like hospitalizations and deaths, regardless of variant. Additionally, this protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222, as supported by our analysis of Asian and relevant international data, and by insights from SEA experts. Given the continued impact of COVID-19 hospitalizations and deaths on health-care systems worldwide, encouraging vaccination strategies that reduce this burden is more relevant than attempting to prevent broader but milder infections with specific variants, including Omicron.


Subject(s)
COVID-19 , SARS-CoV-2 , BNT162 Vaccine , COVID-19/prevention & control , COVID-19 Vaccines , ChAdOx1 nCoV-19 , Humans , Vaccine Efficacy , Vaccines, Inactivated
4.
J Clin Invest ; 132(10)2022 05 16.
Article in English | MEDLINE | ID: covidwho-1846632

ABSTRACT

BackgroundThe Delta and Omicron variants of SARS-CoV-2 are currently responsible for breakthrough infections due to waning immunity. We report phase I/II trial results of UB-612, a multitope subunit vaccine containing S1-RBD-sFc protein and rationally designed promiscuous peptides representing sarbecovirus conserved helper T cell and cytotoxic T lymphocyte epitopes on the nucleocapsid (N), membrane (M), and spike (S2) proteins.MethodWe conducted a phase I primary 2-dose (28 days apart) trial of 10, 30, or 100 µg UB-612 in 60 healthy young adults 20 to 55 years old, and 50 of them were boosted with 100 µg of UB-612 approximately 7 to 9 months after the second dose. A separate placebo-controlled and randomized phase II study was conducted with 2 doses of 100 µg of UB-612 (n = 3,875, 18-85 years old). We evaluated interim safety and immunogenicity of phase I until 14 days after the third (booster) dose and of phase II until 28 days after the second dose.ResultsNo vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. In both trials, UB-612 elicited respective neutralizing antibody titers similar to a panel of human convalescent sera. The most striking findings were long-lasting virus-neutralizing antibodies and broad T cell immunity against SARS-CoV-2 variants of concern (VoCs), including Delta and Omicron, and a strong booster-recalled memory immunity with high cross-reactive neutralizing titers against the Delta and Omicron VoCs.ConclusionUB-612 has presented a favorable safety profile, potent booster effect against VoCs, and long-lasting B and broad T cell immunity that warrants further development for both primary immunization and heterologous boosting of other COVID-19 vaccines.Trial RegistrationClinicalTrials.gov: NCT04545749, NCT04773067, and NCT04967742.FundingUBI Asia, Vaxxinity Inc., and Taiwan Centers for Disease Control, Ministry of Health and Welfare.


Subject(s)
COVID-19 Vaccines , COVID-19 , Adolescent , Adult , Aged , Aged, 80 and over , Antibodies, Neutralizing , Antibodies, Viral , COVID-19/prevention & control , COVID-19/therapy , Humans , Immunization, Passive , Middle Aged , SARS-CoV-2 , T-Lymphocytes , Young Adult
5.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-335168

ABSTRACT

ABSTRACT Importance The SARS-CoV-2 non-spike structural proteins of nucleocapsid (N), membrane (M) and envelope (E) are critical in the host cell interferon response and memory T-cell immunity and have been grossly overlooked in the development of COVID vaccines. Objective To determine the safety and immunogenicity of UB-612, a multitope vaccine containing S1-RBD-sFc protein and rationally-designed promiscuous peptides representing sequence-conserved Th and CTL epitopes on the Sarbecovirus nucleocapsid (N), membrane (M) and spike (S2) proteins. Design, setting and participants UB-612 booster vaccination was conducted in Taiwan. A UB-612 booster dose was administered 6-8 months post-2 nd dose in 1,478 vaccinees from 3,844 healthy participants (aged 18-85 years) who completed a prior placebo (saline)-controlled, randomized, observer-blind, multi-center Phase-2 primary 2-dose series (100-μg per dose;28-day apart) of UB-612. The interim safety and immunogenicity were evaluated until 14 days post-booster. Exposure Vaccination with a booster 3 rd -dose (100-μg) of UB-612 vaccine. Main outcomes and measures Solicited local and systemic AEs were recorded for seven days in the e-diaries of study participants, while skin allergic reactions were recorded for fourteen days. The primary immunogenicity endpoints included viral-neutralizing antibodies against live SARS-CoV-2 wild-type (WT, Wuhan strain) and live Delta variant (VNT 50 ), and against pseudovirus WT and Omicron variant (pVNT 50 ). The secondary immunogenicity endpoints included anti-S1-RBD IgG antibody, S1-RBD:ACE2 binding inhibition, and T-cell responses by ELISpot and Intracellular Staining. Results No post-booster vaccine-related serious adverse events were recorded. The most common solicited adverse events were injection site pain and fatigue, mostly mild and transient. The UB-612 booster prompted a striking upsurge of neutralizing antibodies against live WT Wuhan strain (VNT 50 , 1,711) associated with unusually high cross-neutralization against Delta variant (VNT 50 , 1,282);and similarly with a strong effect against pseudovirus WT (pVNT 50, 6,245) and Omicron variant (pVNT 50 , 1,196). Upon boosting, the lower VNT 50 and pVNT 50 titers of the elderly in the primary series were uplifted to the same levels as those of the young adults. The UB-612 also induced robust, durable VoC antigen-specific Th1-oriented (IFN-γ + -) responses along with CD8 + T-cell (CD107a + -Granzyme B + ) cytotoxicity. Conclusions and relevance With a pronounced cross-reactive booster effect on B- and T-cell immunity, UB-612 may serve as a universal vaccine booster for comprehensive immunity enhancement against emergent VoCs. Trial registration [ClinicalTrials.gov: NCT04773067 ] KEY POINTS Question Facing ever-emergent SARS-CoV-2 variants and long-haul COVID, can composition-updated new vaccines be constructed capable of inducing striking, durable booster-recalled B/T-immunity to prevent infection by VoCs? Findings In a Phase-2 extension study, a booster dose of UB-612 multitope protein-peptide vaccine prompted high viral-neutralizing titers against live wild-type virus (VNT 50 , 1,711), Delta variant (VNT 50 , 1,282);pseudovirus wild-type (pVNT 50 , 6,245) and Omicron variant (pVNT 50 , 1,196). Robust, durable Th1-IFNγ + responses and CD8 + T cell-(CD107a + -Granzyme B + ) cytotoxic activity were both observed. Meaning UB-612 RBD-sFc vaccine armed with T cell immunity-promoting conserved N, M and S2 Th/CTL epitope peptides may serve as a universal vaccine to fend off new VoCs.

6.
EuropePMC; 2022.
Preprint in English | EuropePMC | ID: ppcovidwho-334387

ABSTRACT

Background: COVID-19 vaccines have been highly effective in reducing morbidity and mortality during the pandemic. While primary series vaccination rates are generally high in Southeast Asian (SEA) countries, various factors have limited the rollout and impact of booster doses. Methods: To objectively review the evidence for vaccine effectiveness (VE), we extracted data from 79 studies identified in the publicly-available International Vaccine Access Center (IVAC) VIEW-hub platform reporting VE after a primary immunisation with two-dose schedules for three important clinical outcomes. We evaluated VE after primary immunisation against SARS-CoV-2 infection, and COVID-19-related hospitalisations and deaths for the most widely reported vaccines, stratified across variants of concern (VOC), age, study design and prior SARS-CoV-2 infection. The majority of studies evaluated mRNA vaccines (58 BNT162b2 studies, 34 mRNA-1273 studies and 14 combinations of both) and vector vaccines [25 COVID-19 Vaccine AstraZeneca, Vaxzevria studies (AZD1222)] with only 5 other studies available (all CoronaVac). For simplicity, mRNA studies were grouped together irrespective of which vaccine was used. VE point estimates were presented graphically with pooled means and confidence intervals were compared using standard t-tests for expert discussion. Findings: VE was high and equally effective for both AZD1222 and mRNA vaccines types (91%-93%) in protecting against hospitalisation and death from COVID-19, regardless of age. VE against symptomatic infections trended higher (though not significantly) for mRNA-based vaccines compared to AZD1222. Waning of VE since time of vaccination was observed for symptomatic infections but was limited for serious COVID-19 outcomes. A sub-analysis of studies with comparative arms evaluating the VE of different vaccines in the same settings also confirmed these observations for all VOC assessed, with all vaccines conferring a high level of protection against serious outcomes. For Omicron, there is limited comparative data within the IVAC dataset, however, expert review of emerging data suggests that VE against all outcomes is lower for all COVID-19 vaccines, than for the Delta variant. Importantly, data from the United Kingdom (UK) indicates that VE improves with a booster dose and that VE continues to be very similar, irrespective of the type of vaccine used. Importantly, all COVID-19 vaccines evaluated here have favourable benefit/risk profiles. Interpretation Our review of the robust real-world VE data collated through the IVAC VIEW-hub platform confirms that the most studied COVID-19 vaccines in this database provide consistently high (>90%) protection against serious clinical outcomes like hospitalisations and deaths, and regardless of variant. Additionally, our observation that this protection appears equivalent for mRNA vaccines and vector vaccines like AZD1222 is supported by our analysis of local Asian and relevant international data, and by insights from SEA experts. Given the continued impact of COVID-19 hospitalisations and deaths on healthcare systems worldwide, encouraging vaccination strategies that can reduce this burden is more relevant than attempting to prevent broader but milder infections with specific variants, including Omicron. What this study adds This additional context reinforces the value of real-world evidence to support efforts advocating for the completion of primary series and booster vaccinations where appropriate, especially to restore VE against emerging VOC such as Omicron. However, data gaps still persist, given the lag between the emergence of new variants, updated vaccine schedules and VE data to inform their impact.

7.
EuropePMC; 2020.
Preprint in English | EuropePMC | ID: ppcovidwho-315483

ABSTRACT

Background: After SARS outbreak, infectious control polices had been reformed in Taiwan, but there was no evidence to prove its effectiveness. This study compared emergency department (ED) responses to the SARS and COVID-19 epidemics and investigate how policy changes affect infection prevention. Methods: A 2003 questionnaire regarding the responses of EDs to SARS was resent to EDs during the COVID-19 epidemic in 2020. The use of personal protective equipment (PPE), implementation of infection control measures (ICMs), and difficulties in performance were compared. Data collection included hospital level, different PPE types provided and ICMs implemented, timing for using PPE and ICMs, and a difficulty rating scale for ICM implementation. Results: In total, 100 EDs responded to the questionnaire in 2003 was reviewed and compared with 131 EDs in 2020. In COVID-19 epidemic, the use of basic PPEs and ICMs was mostly significantly improved, but the percentage of preparedness in high grade PPEs was still low. Quarantine of fever patients outside of EDs was less performed in small to medium sized hospitals (p=0.008 and 0.004). All of the additional ICMs were significantly less implemented in local hospitals. The timing to use PPE and implement ICMs were simultaneously and significantly performed at early stage. Instituting a fever triage ward and restricting fever patient admission became less necessary. The closure of EDs remained the most difficult to perform in both outbreaks. Conclusion: After the policy reforms, ED responses became earlier and more consistent. However, inadequate quarantine resources at EDs in low- and middle-grade hospitals may lead to breaches in future epidemics.

8.
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
9.
2021.
Preprint in English | Other preprints | ID: ppcovidwho-296105

ABSTRACT

Summary Background We have assessed the safety and immunogenicity of the COVID-19 vaccine MVC-COV1901, a recombinant protein vaccine containing prefusion-stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminium hydroxide. Methods This is a phase 2, prospective, randomised, double-blind, placebo-controlled, and multi-centre study to evaluate the safety, tolerability, and immunogenicity of the SARS-CoV-2 vaccine candidate MVC-COV1901. The study comprised 3,844 participants of ≥ 20 years who were generally healthy or with stable pre-existing medical conditions. The study participants were randomly assigned in a 6:1 ratio to receive either MVC-COV1901 containing 15 μg of S-2P protein or placebo containing saline. Participants received two doses of MVC-COV1901 or placebo, administered 28 days apart via intramuscular injection. The primary outcomes were to evaluate the safety, tolerability, and immunogenicity of MVC-COV1901 from Day 1 (the day of first vaccination) to Day 57 (28 days after the second dose). Immunogenicity of MVC-COV1901 was assessed through geometric mean titres (GMT) and seroconversion rates (SCR) of neutralising antibody and antigen-specific immunoglobulin. This clinical trial is registered at ClinicalTrials.gov: NCT04695652 . Findings From the start of this phase 2 trial to the time of interim analysis, no vaccine-related Serious Adverse Events (SAEs) were recorded. The most common solicited adverse events across all study participants were pain at the injection site (64%), and malaise/fatigue (35%). Fever was rarely reported (<1%). For all participants in the MVC-COV1901 group, at 28 days after the second dose against wild type SARS-CoV-2 virus, the GMT was 662·3 (408 IU/mL), the GMT ratio was 163·2, and the seroconversion rate was 99·8%. Interpretation MVC-COV1901 shows good safety profiles and promising immunogenicity responses. The current data supports MVC-COV1901 to enter phase 3 efficacy trials and could enable regulatory considerations for Emergency Use Authorisation (EUA). Funding Medigen Vaccine Biologics Corporation and Taiwan Centres for Disease Control.

10.
EuropePMC; 2021.
Preprint in English | EuropePMC | ID: ppcovidwho-291772

ABSTRACT

SARS-CoV-2 breakthrough infection occurs due to waning immunity time-to-vaccine, to which the globally-dominant, highly-contagious Delta variant is behind the scene. In the primary 2-dose and booster series of clinical Phase-1 trial, UB-612 vaccine, which contains S1-RBD and synthetic Th/CTL peptide pool for activation of humoral and T-cell immunity, induces substantial, prolonged viral-neutralizing antibodies that goes parallel with a long-lasting T-cell immunity;and a booster (3rd ) dose can prompt recall of memory immunity to induce profound, striking antibodies with the highest level of 50% viral-neutralizing GMT titers against live Delta variant reported for any vaccine. The unique design of S1-RBD only plus multitope T-cell peptides may have underpinned UB-612’s potent anti-Delta effect, while the other full S protein-based vaccines are affected additionally by mutations in the N-terminal domain sequence which contains additional neutralizing epitopes. UB-612, safe and well-tolerated, could be effective for boosting other vaccine platforms that have shown modest homologous boosting. [Funded by United Biomedical Inc., Asia;ClinicalTrials.gov ID: NCT04967742 and NCT04545749]

11.
Journal of microbiology, immunology, and infection = Wei mian yu gan ran za zhi ; 2021.
Article in English | EuropePMC | ID: covidwho-1451502

ABSTRACT

<h4>Background</h4> Respiratory tract infections (RTIs) represent a major cause of clinical visits worldwide. Viral epidemiology of RTIs in adults has been less studied compared to children. FilmArray respiratory panel (FA-RP), a multiplex, real time polymerase chain reaction method can simultaneously detect the nucleic acids of multiple pathogens. The purpose of this study is to analyze the epidemiology and clinical presentations of an RTI cohort. <h4>Methods</h4> This retrospective cohort study was conducted at China Medical University Hospital (CMUH) and China Medical University Children’s Hospital (CMUCH), from January 2020 to June 2020. The FA-RP results were collected and analyzed according to upper versus lower RTIs. <h4>Results</h4> Among 253 respiratory samples tested, 135 (53.4%) were from adults and 118 (46.6%) from children. A total positive rate of 33.9% (86/253) was found, with 21.48% (29/135) in adults and 48.31% (57/118) in children. Human rhinovirus/Enterovirus (HRV/EV) was detected in most of the age groups and was more common in URIs. HRV/EV was found as a frequent co-detection virus. Among children, HRV/EV was the most detected pathogen of URIs, while the most predominant pathogen in LRIs was M. pneumoniae. <h4>Conclusions</h4> FA-RP has the potential to improve the detection rate of respiratory pathogens. The positive rate of FA-RP was higher in children compared to adults, which likely corresponds to the higher incidence of viral RTIs in children. Different pathogens may lead to different types of respiratory infections.

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