Nonspecific dengue clinical manifestations lead to avoidable antibiotic use. We describe antibiotic use in confirmed pediatric dengue cases and associated healthcare utilization and medical costs, including from antibiotic-associated adverse drug events (ADEs). From Taiwanese national administrative databases, children with confirmed dengue between 2009 and 2015 who were younger than 18 years old, without bacterial infection, and who were prescribed antibiotics a week before or after laboratory diagnosis were propensity score matched and compared with nonrecipients, using regression models for ADEs and medical care expenditures. A total of 1,959 out of 6,938 children (28.2%) with confirmed dengue without bacterial infection received antibiotics. Recipients were more likely to incur emergency department visits (odds ratio [OR]: 3.16; 95% CI: 2.62-3.81), hospitalizations (OR: 4.20; 95% CI: 3.48-5.07), and higher predicted medical care expenditures (new Taiwan dollar [NTD] $16,914 versus NTD $14,104) in a 30-day follow-up period. They also had significantly higher odds of overall defined (OR: 1.72; 95% CI: 1.42-2.09), dermatologic-related (OR: 1.83; 95% CI: 1.36-2.46), and gastrointestinal-related (OR: 1.67; 95% CI: 1.31-2.12) ADEs. A substantial proportion of pediatric patients with dengue received potentially avoidable courses of antibiotics. Recipients were more likely to experience ADEs, incurring more medical care utilization and expenditures than untreated cases.

Inappropriate antibiotic use contributes to antimicrobial resistance, a global public health threat. The non-specific manifestations of dengue, itself a growing public health threat, lead to avoidable empiric antibiotic prescription, particularly in children. In this national pooled population-based cross-sectional study, we evaluated child and physician characteristics associated with antibiotics prescription in confirmed dengue cases in Taiwan. Linking national health care insurance claims and reports of confirmed dengue cases from 2008 to 2015, there were 7086 children with confirmed dengue with 21 744 outpatient visits and 2520 inpatient admissions. We assessed the presence of antibiotic prescription in outpatient and inpatient settings separately a week before or after the confirmation date. Logistic regression models with generalized estimating equations were applied to identify patient, practitioner, and other factors associated with antibiotic prescription. A total of 29.4% of children <18 years old with dengue who did not have a concomitant bacterial infection were prescribed antibiotics during the 14-day assessment period. Antibiotics prescription was reduced from 13.5% to 6.3% and from 43.2% to 19.3% in outpatient and inpatient settings, respectively, after dengue was confirmed. Young children were more likely to receive antibiotics. Significant variations in antibiotic prescribing across physicians were observed only in outpatient settings: physicians >= 60 years old and physicians practicing at clinics and in non-urban facilities were more likely to prescribe antibiotics. Antibiotics were less likely to be prescribed during an exceptional 2-year epidemic than in other years. Antibiotic prescribing for dengue, an arboviral infection affecting half of the global population, was shown to occur in 29% of paediatric cases in Taiwan. That potentially avoidable antibiotic consumption could be reduced by improving antibiotic stewardship, informed by understanding the conditions under which antibiotics are prescribed and the availability of prevention strategies for viral diseases, including dengue. We identified a number of such factors in this national population-based study.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines based on variant strains have been in use as booster doses to update immunity against circulating variants. Here we present the results of a phase one prospective, randomized, and open-labeled trial to study the safety and immunogenicity of a booster dose consisting of a subunit vaccine based on the stabilized prefusion SARS-CoV-2 spike protein, MVC-COV1901, or its Beta version, MVC-COV1901-Beta. Participants aged ≥18 and <55 years who received two or three prior doses of MVC-COV1901 vaccines were enrolled and were to receive a booster dose of either 15 mcg of MVC-COV1901, 15 mcg, or 25 mcg of MVC-COV1901-Beta in a 1:1:1 ratio. Adverse reactions after either MVC-COV1901 or MVC-COV1901-Beta booster doses after two or three doses of MVC-COV1901 were comparable and mostly mild and transient. At four weeks after the booster dose, participants with two prior doses of MVC-COV1901 had higher levels of neutralizing antibodies against ancestral SARS-CoV-2, Beta, and Omicron variants than participants with three prior doses of MVC-COV1901, regardless of the type of booster used. MVC-COV1901 and MVC-COV1901-Beta can both be effectively used as booster doses against SARS-CoV-2, including the BA.4/BA.5 Omicron variants.

Background: This study aimed to assess the safety and immunogenicity of MVC-COV1901, a recombinant COVID-19 protein vaccine, containing S-2P protein adjuvanted with CpG 1018 and aluminum hydroxide, for people living with HIV (PWH). Methods: A total of 57 PWH of ≥20 years of age who are on stable antiretroviral therapy were compared with 882 HIV-negative participants. Participants received two doses of MVC-COV1901 28 days apart. Results: No vaccine-related serious adverse events (SAEs) were recorded. Seroconversion rates (SCRs) of 100% and 99.8% were achieved in PWH and comparators, respectively, 28 days after the second dose. After adjusting for sex, age, BMI category, and comorbidity, the adjusted GMT ratio of comparator/PWH was 3.2 (95% CI 2.5–4). A higher CD4/CD8 ratio was associated with a higher GMT (R = 0.27, p = 0.039). MVC-COV1901 has shown robust safety but elicited weaker immune responses in PWH. Conclusions: Further investigations may be needed to determine whether PWH require distinct immunization strategies with improved immunogenicity. The main study is registered at ClinicalTrials.gov (NCT04695652).

Dengue, a mosquitoborne flavivirus infection, is increasingly a disease of older adults who are more likely to have chronic diseases that confer risk for severe outcomes of dengue infection. In a population-based study in Taiwan, adjusted risks for dengue-related hospitalization, intensive care unit admission, and death increased progressively with age.

The Brighton Collaboration Benefit-Risk Assessment of VAccines by TechnolOgy (BRAVATO) Working Group has prepared standardized templates to describe the key considerations for the benefit-risk assessment of several vaccine platform technologies, including protein subunit vaccines. This article uses the BRAVATO template to review the features of the MVC-COV1901 vaccine, a recombinant protein subunit vaccine based on the stabilized pre-fusion SARS-CoV-2 spike protein S-2P, adjuvanted with CpG 1018 and aluminum hydroxide, manufactured by Medigen Vaccine Biologics Corporation in Taiwan. MVCCOV1901 vaccine is indicated for active immunization to prevent COVID-19 caused by SARS-CoV-2 in individuals 12 years of age and older. The template offers details on basic vaccine information, target pathogen and population, characteristics of antigen and adjuvant, preclinical data, human safety and efficacy data, and overall benefit-risk assessment.The clinical development program began in September 2020 and based on demonstration of favorable safety and immunogenicity profiles in 11 clinical trials in over 5,000 participants, it has been approved for emergency use based on immunobridging results for adults in Taiwan, Estwatini, Somaliland, and Paraguay. The main clinical trials include placebo-controlled phase 2 studies in healthy adults (CTCOV-21), adolescents (CT-COV-22), and elderly population (CT-COV-23) as well as 3 immunobridging phase 3 trials (CT-COV-31, CT-COV-32, and CT-COV-34) in which MVC-COV1901 was compared to AZD1222. There are also clinical trials studying MVC-COV1901 as homologous and heterologous boosters (CT-COV-24 and CT-COV-25). The totality of evidence based on -3 million vaccinees to date includes a mostly clean safety profile, with adverse events mostly being mild and self-limiting in both clinical development and postmarketing experience, proven immunogenic response, and real-world effectiveness data. The immunogenic profile demonstrates that MVC-COV1901 induces high levels of neutralizing and binding antibodies against SARS-CoV-2. There is a dose-dependent response and a significant correlation between binding and neutralizing antibody activity. Antigen-specific T-cell responses, particularly a Th1-biased immune response characterized by high levels of interferon gamma and IL-2 cytokines, have also been observed. Coupled with this, MVC-COV1901 has favorable thermostability and better safety profiles when compared to other authorized vaccines from different platforms, which make it potentially a good candidate for vaccine supply chains in global markets. (c) 2023 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Background/Purpose: MVC-COV1901 is a protein vaccine based on the same SARS-CoV-2 strain used in mRNA vaccine mRNA-1273. Data are lacking on immunogenicity and safety of MVC-COV1901 as heterologous boost for people already received one dose of mRNA-1273.Methods: This is a randomized, double-blind trial that recruited adults aged 20-70 years who previously received a single dose of mRNA-1273 vaccine and were randomly assigned in a 1:1 ratio to receive a second dose with the homologous vaccine or protein-based MVC-COV1901 8-12 weeks after the first dose. The primary outcome was neutralizing antibody titers in terms of the geometric mean titer (GMT) 14 days after the second dose. Safety was assessed in all participants who received a dose of the study vaccine. The study is registered with ClinicalTrials.gov (NCT05079633).Results: From September 30 to November 5, 2021, 144 participants were enrolled and randomly assigned to the MVC-COV1901 boost group (n = 72) or the mRNA-1273 boost group (n = 72). The neutralizing antibodies on Day 15 and the anti-SARS-CoV-2 IgG titers on Day 15 and 29 of homologous mRNA-1273 were significantly higher than those of heterologous mRNA-1273/MVC-COV1901. Cellular immune responses were comparable in both groups. How-ever, adverse events were much more frequent after the mRNA-1273 boost than after the MVC-COV1901 boost.Conclusion: Our results show that heterologous boost with MVC-COV1901 yielded an inferior immunogenicity but significantly fewer adverse events, compared with homologous boost withmRNA-1273. In people experienced severe adverse events after prime dose of mRNA-1273, as well as in periods when the supply of mRNA-1273 is limited, MVC-COV1901 could serve as an acceptable alternative heterologous boost.Copyright (c) 2023, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

OBJECTIVES:To report the safety and immunogenicity profile of a protein subunit vaccine (MVC-COV1901) compared to AZD1222 and mRNA-1273 when given as a third (booster) dose to individuals who have completed different primary vaccine regimens. METHODS:Individuals were classified according to their primary vaccine regimens, including two-dose MVC-COV1901, AZD1222, or mRNA-1273. A third dose of either half-dose MVC-COV1901, full-dose MVC-COV1901, standard-dose AZD1222, half-dose mRNA-1273 was administered in a 1:1:1:1 treatment ratio to individuals with an interval range of 84-365 days after the second dose. Endpoints included safety, humoral immunogenicity, and cell-mediated immune response on trial days 15 and 29. Exploratory endpoint included testing against variants of concern (Omicron). RESULTS:Overall, 803 participants were randomized and boosted - 201 received half-dose MVC-COV1901, 196 received full-dose MVC-COV1901, 203 received AZD1222, and 203 received half-dose mRNA-1273. Reactogenicity was mild to moderate, and less in the MVC-COV1901 booster group. Heterologous boosting provided the best immunogenic response. Boosting with mRNA-1273 in MVC-COV1901 primed individuals induced the highest antibody titers, even against Omicron, and cell-mediated immune response. CONCLUSIONS:Overall, MVC-COV1901 as a booster showed the best safety profiles. MVC-COV1901 as a primary series, with either homologous or heterologous booster, elicited the highest immunogenic response. CLINICALTRIALS:gov registration NCT05197153.

Background: Data from previous studies of the MVC-COV1901 vaccine, a subunit vaccine against SARS-CoV-2 based on the stable prefusion spike protein (S-2P) adjuvanted with CpG 1018 adjuvant and aluminum hydroxide, suggest that the vaccine is generally safe and elicits a good immune response in healthy adults and adolescents. By comparing with AZD1222, this study adds to the findings from previous trials and further evaluates the breadth of protection offered by MVC-COV1901. Methods: In this phase 3, parallel group, randomized, double-blind, active-controlled trial conducted in 2 sites in Paraguay, we assigned adults aged 18-91 years in a 1:1 ratio to receive intramuscular doses of MVC-COV1901 or AZD1222 administered as scheduled in the clinical trial. Serum samples were collected on the day of vaccination and 14 days after the second dose. Primary and secondary safety and immunogenicity endpoints were assessed. In addition, other outcomes investigated were cross-reactive immunity against the Omicron strain and the induction of IgG subclasses. Results: A total of 1,030 participants underwent randomization. Safety data was derived from this set while primary immunogenicity data involved a per-protocol immunogenicity (PPI) subset including 225 participants. Among the participants, 58% are seropositive at baseline. When compared against AZD1222, MVC-COV1901 exhibited superiority in terms of neutralizing antibody titers and non -inferiority in terms of seroconversion rates. Reactogenicity was generally mild and no serious adverse event was attributable to MVC-COV1901. Both vaccines have a Th1-biased response predominated by the production of IgG1 and IgG3 subclasses. Omicron-neutralizing titers were 44.5 times lower compared to wildtype-neutralizing titers among seronegative individuals at baseline. This fold-reduction was 3.0 times among the seropositive. Conclusion: Safety and immunogenicity data of MVC-COV1901 from the study in Paraguay confirm previous results. The previous infection coupled with vaccination of this vaccine may offer protection against the Omicron strain though its durability is still unknown. (c) 2022 Published by Elsevier Ltd.

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. 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. 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. Our data showed increased persistence of neutralizing antibodies and enhancement of immunogenicity against VoCs offered after a third dose of MVC-COV1901. ClinicalTrials.gov identifier NCT04487210.

The dominance of SARS-CoV-2 variants of concern (VoC), such as the Omicron subvariants, is a threat to the current vaccination scheme due to increased resistance to immune neutralization and greater transmissibility. To develop the next generation of prefusion SARS-CoV-2 spike protein (S-2P) subunit vaccine adjuvanted with CpG1018 and aluminum hydroxide, mice immunized with two doses of the adjuvanted ancestral Wuhan strain (W) followed by the third dose of the W or Omicron variants (BA.1 or BA.4/BA.5) S-2P, or a combination of the above bivalent S-2Ps. Antisera from mice were tested against pseudovirus neutralization assay of ancestral SARS-CoV-2 (WT) and Omicron BA.4/BA.5 subvariant. Boosting with bivalent mixture of Omicron BA.4/BA.5 and W S-2P achieved the highest neutralizing antibody titers against BA.4/BA.5 subvariant pseudovirus compared to other types of S-2P as boosters.

Adolescents and children play an important role in SARS-CoV-2 transmission and epidemiology. MVC-COV1901 is a subunit SARS-CoV-2 vaccine based on stabilized spike protein adjuvanted with CpG 1018 and aluminum hydroxide that has received emergency use approval (EUA) for adults in Taiwan. In this study, we have investigated the safety and immunogenicity of two doses of MVC-COV1901 in adolescents. Healthy adolescents from the age of 12–17 years were randomly assigned to receive two intramuscular doses of either MVC-COV1901 or placebo at 28 days apart. Adverse events were mostly mild and were similar in MVC-COV1901 and placebo groups, with the most commonly reported adverse events being pain/tenderness and malaise/fatigue. All immunogenicity endpoints in the adolescent group were non-inferior to the endpoints seen in the young adult and placebo groups. The results here advocate the use of MVC-COV1901 in adolescents in the ongoing efforts to control the pandemic. ClinicalTrials.gov registration : NCT04951388.

Abstract Background Variants of concern (VoCs) have the potential to diminish the neutralizing capacity of antibodies elicited by vaccines. MVC-COV1901 is a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine consisting of recombinant prefusion stabilized spike protein S-2P adjuvanted with CpG 1018 and aluminum hydroxide. We explored the effectiveness of MVC-COV1901 against the VoCs. Methods Serum samples were taken from rats and phase 1 clinical trial human subjects immunized with a low, medium, or high dose of MVC-COV1901. The neutralizing titers of serum antibodies were assayed with pseudoviruses coated with the SARS-CoV-2 spike protein of the wild-type (WT), D614G, Alpha, or Beta variants. Results Rats vaccinated twice with vaccine containing high doses of antigen retained high levels of neutralization activity against the Beta variant, albeit with a slight reduction compared to WT. After the third dose, neutralizing titers against the Beta variant were noticeably enhanced regardless of the amount of antigen used for immunization. In humans, vaccinated phase 1 subjects still showed appreciable neutralization abilities against the D614G, Alpha, and Beta variants, although neutralizing titers were significantly reduced against the Beta variant. Conclusions Two doses of MVC-COV1901 were able to elicit neutralizing antibodies against SARS-CoV-2 variants with an overall tendency of inducing higher immune response at a higher dose level. The neutralizing titers to the Beta variant in rats and humans were lower than those for WT and the Alpha variant. An additional third dose in rats was able to partially compensate for the reduction in neutralization against the Beta variant. We have demonstrated that immunization with MVC-COV1901 was effective against VoCs.

BackgroundAntibiotic treatment for dengue is likely considerable and potentially avoidable but has not been well characterized. This study aimed to assess antibiotic prescribing for confirmed dengue cases in outpatient and inpatient settings and to identify associated patient, physician and contextual factors. Methods57,301 adult dengue cases reported in Taiwan between 2008-2015 were analyzed. We assessed both outpatient and inpatient claims data of dengue patients from a week before to a week after their dengue infections were confirmed under Taiwan's National Health Insurance program. A multivariable logistic regression with generalized estimating equations was used to estimate the probability of antibiotic prescribing in dengue patients. ResultsOverall, 24.6% of dengue patients were prescribed an antibiotic during the 14 day-assessment period. Antibiotics were prescribed in 6.1% and 30.1% of outpatient visits and inpatient admissions, respectively. Antibiotic prescriptions were reduced by ~50% in epidemic years. Among inpatients, advanced age, females, and major comorbidities were risk factors for receipt of an antibiotic; antibiotics were used in 26.0% of inpatients after dengue was diagnosed. Significant differences in antibiotic prescribing practices were observed among physicians in outpatient settings but not in inpatient settings. ConclusionsIn addition to patient and physician demographic characteristics, contextual factors such as care setting and during epidemics significantly influenced prescription of antibiotics. Characterization of prescribing patterns should help direct programs to curb antibiotic prescribing. Author summaryAntimicrobial resistance is a growing global public health threat. The non-specific clinical manifestations of dengue overlap with signs and symptoms of other febrile illnesses common to tropical and subtropical zones making differential diagnosis between dengue and bacterial infections difficult, hence, leading to potentially unnecessary antibiotic prescribing. However, our understanding of factors underlying antibiotic prescribing for dengue is rather limited. Taiwan has experienced periodic dengue outbreaks and has a comprehensive national health insurance database including reliable infectious diseases surveillance and prescribing records. The findings in Taiwan show that other than commonly known patient characteristics, provider and contextual factors play a significant role. Physician's age and practice setting were significant factors influencing the decision to prescribe antibiotics, particularly in outpatient visits. The likelihood of prescribing an antibiotic to dengue patients was reduced by more than 50% in medical visits occurring after the dengue infection was confirmed. Understanding patient, provider and contextual factors in antibiotics prescription for dengue infections can provide insights for improved antibiotic stewardship and unnecessary antibiotic treatment for dengue.

With the rapid progress made in the development of vaccines to fight the SARS-CoV-2 pandemic, almost >90% of vaccine candidates under development and a 100% of the licensed vaccines are delivered intramuscularly (IM). While these vaccines are highly efficacious against COVID-19 disease, their efficacy against SARS-CoV-2 infection of upper respiratory tract and transmission is at best temporary. Development of safe and efficacious vaccines that are able to induce robust mucosal and systemic immune responses are needed to control new variants. In this study, we have used our nanoemulsion adjuvant (NE01) to intranasally (IN) deliver stabilized spike protein (S-2P) to induce immunogenicity in mouse and hamster models. Data presented demonstrate the induction of robust immunity in mice resulting in 100% seroconversion and protection against SARS-CoV-2 in a hamster challenge model. There was a significant induction of mucosal immune responses as demonstrated by IgA- and IgG-producing memory B cells in the lungs of animals that received intranasal immunizations compared to an alum adjuvanted intramuscular vaccine. The efficacy of the S-2P/NE01 vaccine was also demonstrated in an intranasal hamster challenge model with SARS-CoV-2 and conferred significant protection against weight loss, lung pathology, and viral clearance from both upper and lower respiratory tract. Our findings demonstrate that intranasal NE01-adjuvanted vaccine promotes protective immunity against SARS-CoV-2 infection and disease through activation of three arms of immune system: humoral, cellular, and mucosal, suggesting that an intranasal SARS-CoV-2 vaccine may play a role in addressing a unique public health problem and unmet medical need.

Background: Administration of potent anti-receptor-binding domain (RBD) monoclonal antibodies has been shown to curtail viral shedding and reduce hospitalization in patients with SARS-CoV-2 infection. However, the structure-function analysis of potent human anti-RBD monoclonal antibodies and its links to the formulation of antibody cocktails remains largely elusive. Methods: Previously, we isolated a panel of neutralizing anti-RBD monoclonal antibodies from convalescent patients and showed their neutralization efficacy in vitro. Here, we elucidate the mechanism of action of antibodies and dissect antibodies at the epitope level, which leads to a formation of a potent antibody cocktail. Results: We found that representative antibodies which target non-overlapping epitopes are effective against wild type virus and recently emerging variants of concern, whilst being encoded by antibody genes with few somatic mutations. Neutralization is associated with the inhibition of binding of viral RBD to ACE2 and possibly of the subsequent fusion process. Structural analysis of representative antibodies, by cryo-electron microscopy and crystallography, reveals that they have some unique aspects that are of potential value while sharing some features in common with previously reported neutralizing monoclonal antibodies. For instance, one has a common VH 3-53 public variable region yet is unusually resilient to mutation at residue 501 of the RBD. We evaluate the in vivo efficacy of an antibody cocktail consisting of two potent non-competing anti-RBD antibodies in a Syrian hamster model. We demonstrate that the cocktail prevents weight loss, reduces lung viral load and attenuates pulmonary inflammation in hamsters in both prophylactic and therapeutic settings. Although neutralization of one of these antibodies is abrogated by the mutations of variant B.1.351, it is also possible to produce a bi-valent cocktail of antibodies both of which are resilient to variants B.1.1.7, B.1.351 and B.1.617.2. Conclusions: These findings support the up-to-date and rational design of an anti-RBD antibody cocktail as a therapeutic candidate against COVID-19.

IntroductionOlder 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.MethodsA 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.ResultsBoth 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.ConclusionGiven 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).

Abstract Older adults are subject to higher COVID-19 infection and mortality rates. Even though vaccination programs prioritize the elderly, they are under-represented in clinical trials. Safety and immunogenicity of MVC-COV1901, a protein subunit vaccine has been demonstrated in phase 2 clinical trial for the general population, and negative correlations have been observed between immune responses and age. To further assess safety and immunogenicity of MVC-COV1901 vaccine in participants of 65 years and older, a double-blind, randomized, multi-center study compared high-dose (25 mcg) to mid-dose (15 mcg) of MVC-COV1901 administered 2 times 28 days apart. The results have been stratified by the comorbidity status. 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. Given the general population-associated safety and immunogenicity of MVC-COV1901, we recommended high dose for the elderly.