Safety of COVID-19 vaccines in multiple sclerosis: A systematic review and meta-analysis.

BACKGROUND: Data are sparse regarding the safety of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in patients with multiple sclerosis (MS). OBJECTIVE: To estimate (1) the pooled proportion of MS patients experiencing relapse among vaccine recipients; (2) the rate of transient neurological worsening, adverse events, and serious adverse events; (3) the previous outcomes of interest for different SARS-CoV-2 vaccine types. METHODS: Systematic review and meta-analysis of pharmacovigilance registries and observational studies. RESULTS: Nineteen observational studies comprising 14,755 MS patients who received 23,088 doses of COVID-19 vaccines were included. Mean age was 43.3 years (95% confidence interval (CI): 40-46.6); relapsing-remitting, secondary-progressive, primary-progressive MS and clinically isolated syndrome were diagnosed in 82.6% (95% CI: 73.9-89.8), 12.6% (95% CI: 6.3-20.8), 6.7% (95% CI: 4.2-9.9), and 2.9% (95% CI: 1-5.9) of cases, respectively. The pooled proportion of MS patients experiencing relapse at a mean time interval of 20 days (95% CI: 12-28.2) from vaccination was 1.9% (95% CI: 1.3%-2.6%; I2 = 78%), with the relapse risk being independent of the type of administered SARS-CoV-2-vaccine (p for subgroup differences = 0.7 for messenger RNA (mRNA), inactivated virus, and adenovector-based vaccines). After vaccination, transient neurological worsening was observed in 4.8% (95% CI: 2.3%-8.1%) of patients. Adverse events and serious adverse events were reported in 52.8% (95% CI: 46.7%-58.8%) and 0.1% (95% CI: 0%-0.2%) of vaccinations, respectively. CONCLUSION: COVID-19 vaccination does not appear to increase the risk of relapse and serious adverse events in MS. Weighted against the risks of SARS-CoV-2-related complications and MS exacerbations, these safety data provide compelling pro-vaccination arguments for MS patients.

Effectiveness of the Ad26.COV2.S (Johnson & Johnson) Coronavirus Disease 2019 (COVID-19) Vaccine for Preventing COVID-19 Hospitalizations and Progression to High Disease Severity in the United States.

Background . Adults in the United States (US) began receiving the adenovirus vector coronavirus disease 2019 (COVID-19) vaccine, Ad26.COV2.S (Johnson & Johnson [Janssen]), in February 2021. We evaluated Ad26.COV2.S vaccine effectiveness (VE) against COVID-19 hospitalization and high disease severity during the first 10 months of its use. Methods . In a multicenter case-control analysis of US adults (≥18 years) hospitalized 11 March to 15 December 2021, we estimated VE against susceptibility to COVID-19 hospitalization (VEs), comparing odds of prior vaccination with a single dose Ad26.COV2.S vaccine between hospitalized cases with COVID-19 and controls without COVID-19. Among hospitalized patients with COVID-19, we estimated VE against disease progression (VEp) to death or invasive mechanical ventilation (IMV), comparing odds of prior vaccination between patients with and without progression. Results . After excluding patients receiving mRNA vaccines, among 3979 COVID-19 case-patients (5% vaccinated with Ad26.COV2.S) and 2229 controls (13% vaccinated with Ad26.COV2.S), VEs of Ad26.COV2.S against COVID-19 hospitalization was 70% (95% confidence interval [CI]: 63-75%) overall, including 55% (29-72%) among immunocompromised patients, and 72% (64-77%) among immunocompetent patients, for whom VEs was similar at 14-90 days (73% [59-82%]), 91-180 days (71% [60-80%]), and 181-274 days (70% [54-81%]) postvaccination. Among hospitalized COVID-19 case-patients, VEp was 46% (18-65%) among immunocompetent patients. Conclusions . The Ad26.COV2.S COVID-19 vaccine reduced the risk of COVID-19 hospitalization by 72% among immunocompetent adults without waning through 6 months postvaccination. After hospitalization for COVID-19, vaccinated immunocompetent patients were less likely to require IMV or die compared to unvaccinated immunocompetent patients.

SARS-CoV-2 vaccine development

SARS-CoV-2 is a well-known viral strain that causes COVID-19. The disease became a pandemic in early 2020 and infected millions of people and killed hundreds of thousands of people worldwide. Vaccine development against the disease was accelerated with multiple collaborations among research institutions in order to shorten the duration that vaccine development normally takes. Prior coronavirus vaccines present a basis on which vaccines against the current strain can be developed with much speed and relative ease. Among the patented coronavirus vaccines, DNA-based vaccine had the most patents registered which must have clues to guide the efforts in the current works. This work presents some progress on COVID-19 vaccine development and also possible animal venom protein sources that can potentially be used in the pipeline. The future of COVID-19 vaccine is bright with the heightened collaborative efforts and data sharing opportunities that the pandemic has brought among researchers. © 2022 Elsevier Inc. All rights reserved.

Development of Modified Vaccinia Virus Ankara-Based Vaccines: Advantages and Applications.

Modified vaccinia virus Ankara (MVA) is a promising viral vector for vaccine development. MVA is well studied and has been widely used for vaccination against smallpox in Germany. This review describes the history of the origin of the virus and its properties as a vaccine, including a high safety profile. In recent years, MVA has found its place as a vector for the creation of vaccines against various diseases. To date, a large number of vaccine candidates based on the MVA vector have already been developed, many of which have been tested in preclinical and clinical studies. We discuss data on the immunogenicity and efficacy of some of these vaccines.

Vaccines against SARS-CoV-2

The pandemic caused by the novel coronavirus, SARS-CoV-2, first detected in December 2019, resulted in millions of deaths and more than a hundred million confirmed infections in the first 18 months. COVID-19, the disease caused by SARS-CoV-2, is asymptomatic for some, for others it can cause illness ranging from mild flu-like symptoms with the most serious cases manifesting with acute respiratory distress syndrome (ARDS), pneumonia and death. The worldwide effort to develop effective vaccines against COVID-19 and SARS-CoV-2 has been unparalleled throughout history. At the time of writing, there are more than 100 candidate vaccines in clinical development and almost 200 undergoing pre-clinical testing, around the world. These diverse candidates use a range of vaccine strategies and platforms including several relatively novel approaches. Many of these newer strategies have been approved for emergency use and existing data advocate for the critical role that they may have in protecting individuals and reducing the ongoing pandemic. This chapter focusses on nucleic acid and viral vector-based vaccines, currently undergoing post-licensure surveillance, being the most widespread technologies used against the pandemic. As well as reviewing the different vaccine platforms and vaccine candidates, this chapter discusses the events preceding the COVID-19 pandemic that allowed vaccine development to occur at never-before-seen speed, the biological and immunological basis for a SARS-CoV-2 vaccine, the importance of collaborative international efforts and the broad lessons that can be applied towards future pandemics. © 2022 Elsevier Inc. All rights reserved.

The repeated setbacks of HIV vaccine development laid the groundwork for SARS-CoV-2 vaccines.

The decades-long effort to produce a workable HIV vaccine has hardly been a waste of public and private resources. To the contrary, the scientific know-how acquired along the way has served as the critical foundation for the development of vaccines against the novel, pandemic SARS-CoV-2 virus. We retell the real-world story of HIV vaccine research - with all its false leads and missteps - in a way that sheds light on the current state of the art of antiviral vaccines. We find that HIV-related R&D had more than a general spillover effect. In fact, the repeated failures of phase 2 and 3 clinical trials of HIV vaccine candidates have served as a critical stimulus to the development of successful vaccine technologies today. We rebut the counterargument that HIV vaccine development has been no more than a blind alley, and that recently developed vaccines against COVID-19 are really descendants of successful vaccines against Ebola, MERS, and SARS. These successful vaccines likewise owe much to the vicissitudes of HIV vaccine development. We then discuss how the failures of HIV vaccine development have taught us how adapt SARS-CoV-2 vaccines to immune escape from emerging variants. Finally, we inquire whether recent advances in the development of vaccines against SARS-CoV-2 might in turn further the development of an HIV vaccine - what we describe as a reverse spillover effect.

Antibody response after two doses of homologous or heterologous SARS-CoV-2 vaccines in healthcare workers at health promotion centers: A prospective observational study.

Assaying of anti-spike-protein receptor-binding domain (S-RBD) antibodies are used to aid evaluations of the immune statuses of individuals. The aim of this study was to determine the antibody response after two doses of homologous or heterologous severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines and to identify the factors affecting this response among healthcare workers (HCWs) at health promotion centers. In this prospective observational study, 1095 consenting HCWs were recruited from 16 health checkup centers and were tested at T0 (day of first dose), T1-1 (1 month after first dose), T2-0 (day of second dose), T2-1 (1 month after second dose), and T2-3 (3 months after second dose). SARS-CoV-2 antibodies were measured using a chemiluminescence microparticle immunoassay with SARS-CoV-2 IgG II Quant in the ARCHITECT system (Abbott Diagnostics). At T1-1, anti-SARS-CoV-2 S-RBD IgG levels were significantly higher in participants who received messenger RNA (mRNA) vaccines than in those who received viral vector vaccines (p < 0.001). At T2-1, anti-SARS-CoV-2 S-RBD IgG levels were about 10 times higher than at T1-1 in participants who received homologous mRNA vaccines, which decreased to a third of those at T2-3. Anti-SARS-CoV-2 S-RBD IgG levels were highest among those who received homologous mRNA vaccines, followed by heterologous mRNA viral vector vaccines and homologous viral vector vaccines at T2-3 (p < 0.001). In a multivariable linear regression analysis, being female, taking at least one mRNA vaccine, and having a history of recovery from coronavirus disease 2019 (COVID-19) were significantly associated with anti-S-RBD levels. Anti-SARS-CoV-2 S-RBD IgG levels were decreased at 3 months after two-dose vaccinations and were associated with sex, vaccine type, and COVID-19 history.

Myocarditis following AstraZeneca (an adenovirus vector vaccine) COVID-19 vaccination: A case report.

Coronavirus disease-19 (COVID-19) vaccines are massively administered globally and some adverse events, such as myocarditis, are being reported. Most of the reported cases of post-vaccination myocarditis have occurred following mRNA vaccinations. However, there have also been recent reports of myocarditis following adenovirus vector vaccinations. We present a case of a 32-year-old female patient who developed myocarditis following the administration of the first dose of the AstraZeneca vaccine. The patient developed inappropriate exertional tachycardia and exertional dyspnea from Day 3 and was diagnosed with myocarditis by subsequent echocardiography about 3 months later. We are unable to confirm a direct association between myocarditis and AstraZeneca vaccination. However, we would like to increase awareness regarding the possibility of developing myocarditis following AstraZeneca vaccination.

Incidence and Risk Factors of COVID-19 Vaccine Breakthrough Infections: A Prospective Cohort Study in Belgium.

The objective of this study was to investigate the incidence and risk factors associated with COVID-19 vaccine breakthrough infections. We included all persons ≥18 years that had been fully vaccinated against COVID-19 for ≥14 days, between 1 February 2021 and 5 December 2021, in Belgium. The incidence of breakthrough infections (laboratory confirmed SARS-CoV-2-infections) was determined. Factors associated with breakthrough infections were analyzed using COX proportional hazard models. Among 8,062,600 fully vaccinated adults, we identified 373,070 breakthrough infections with an incidence of 11.2 (95%CI 11.2-11.3)/100 person years. Vaccination with Ad26.COV2.S (HR1.54, 95%CI 1.52-1.56) or ChAdOx1 (HR1.68, 95%CI 1.66-1.69) was associated with a higher risk of a breakthrough infection compared to BNT162b2, while mRNA-1273 was associated with a lower risk (HR0.68, 95%CI 0.67-0.69). A prior COVID-19-infection was protective against a breakthrough infection (HR0.23, 95%CI 0.23-0.24), as was an mRNA booster (HR0.44, 95%CI 0.43-0.45). During a breakthrough infection, those who had a prior COVID-19 infection were less likely to have COVID-19 symptoms of almost all types than naïve persons. We identified risk factors associated with breakthrough infections, such as vaccination with adenoviral-vector vaccines, which could help inform future decisions on booster vaccination strategies. A prior COVID-19 infection lowered the risk of breakthrough infections and of having symptoms, highlighting the protective effect of hybrid immunity.

Vaccine effectiveness against severe acute respiratory infections (SARI) COVID-19 hospitalisations estimated from real-world surveillance data, Slovenia, October 2021.

We estimated vaccine effectiveness (VE) against severe COVID-19 during October 2021, using Slovenian surveillance data. For people fully vaccinated with any vaccine in age groups 18-49, 50-64, ≥ 65 years, VE was 86% (95% CI: 79-90), 89% (85-91), and 77% (74-81). Among ≥ 65 year-olds fully vaccinated with mRNA vaccines, VE decreased from 93% (95% CI: 88-96) in those vaccinated ≤ 3 months ago to 43% (95% CI: 30-54) in those vaccinated ≥ 6 months ago, suggesting the need for early boosters.

International Nonproprietary Names (INN) for novel vaccine substances: A matter of safety.

International Nonproprietary Names (INN) are assigned by the World Health Organization (WHO) to pharmaceutical substances to ensure global recognition by a unique name. INN facilitate safe prescribing through naming consistency, efficient communication and exchange of information, transnational access and pharmacovigilance of medicinal products. Traditional vaccines such as inactivated or live-attenuated vaccines have not been assigned INN and provision of a general name falls within the scope of the WHO Expert Committee on Biological Standardization (ECBS). However, novel vaccines that contain well-defined active ingredients such as nucleic acids or recombinant proteins fulfil the criteria to be assigned INN. In the current environment where multiple SARS-CoV-2 vaccines are being developed to combat the COVID-19 pandemic and with virus variants emerging, assigning INN to well-defined vaccine substances will strengthen pharmacovigilance and ultimately enhance the safety of vaccine recipients. This article examines the background to INN for vaccines and explains the applicability and value of assigning INN to novel well-defined vaccines.

A focused review on technologies, mechanisms, safety, and efficacy of available COVID-19 vaccines.

>20 months has been passed since the detection of the first cases of SARS-CoV-2 infection named COVID-19 from Wuhan city of China. This novel coronavirus spread rapidly around the world and became a pandemic. Although different therapeutic options have been considered and approved for the management of COVID-19 infection in different stages of the disease, challenges in pharmacotherapy especially in patients with moderate to severe COVID-19 and with underlying diseases have still remained. Prevention of infection through public vaccination would be the only efficient strategy to control the morbidity and mortality caused by COVID-19. To date, several COVID-19 vaccines using different platforms including nucleic acid-based vaccines, adenovirus-based vaccines, protein-based vaccines, and inactivated vaccines have been introduced among which many have received approval for prevention against COVID-19. In this comprehensive review, available COVID-19 vaccines have been discussed. The mechanisms, safety, efficacy, dosage, dosing intervals, possible adverse reactions, storage, and coverage of these four different vaccine platforms against SARS-CoV-2 variants have been discussed in detail and summarized in tabular format for ease of comparison and conclusion. Although each COVID-19 vaccine has various advantages and disadvantages over the others, accessibility and affordability of approved vaccines by the official health organizations, especially in developing countries, would be essential to terminate this pandemic. The main limitation of this study was the lack of access to the clinical data on available COVID-19 vaccines developed in Eastern countries since the data on their efficacy, safety, and adverse reactions were limited.

Why are we vaccinating children against COVID-19?

This article examines issues related to COVID-19 inoculations for children. The bulk of the official COVID-19-attributed deaths per capita occur in the elderly with high comorbidities, and the COVID-19 attributed deaths per capita are negligible in children. The bulk of the normalized post-inoculation deaths also occur in the elderly with high comorbidities, while the normalized post-inoculation deaths are small, but not negligible, in children. Clinical trials for these inoculations were very short-term (a few months), had samples not representative of the total population, and for adolescents/children, had poor predictive power because of their small size. Further, the clinical trials did not address changes in biomarkers that could serve as early warning indicators of elevated predisposition to serious diseases. Most importantly, the clinical trials did not address long-term effects that, if serious, would be borne by children/adolescents for potentially decades. A novel best-case scenario cost-benefit analysis showed very conservatively that there are five times the number of deaths attributable to each inoculation vs those attributable to COVID-19 in the most vulnerable 65+ demographic. The risk of death from COVID-19 decreases drastically as age decreases, and the longer-term effects of the inoculations on lower age groups will increase their risk-benefit ratio, perhaps substantially.

Factors Affecting Hesitancy to mRNA and Viral Vector COVID-19 Vaccines among College Students in Italy.

Vaccine hesitancy (VH) may be significant in jeopardizing efforts to mass containment of COVID-19. A cross-sectional survey was carried out on a sample of 2667 Italian college students, before the COVID-19 vaccines became available for this age group (from 7 May to 31 May 2021). An online survey was created to obtain information about socio-demographic, health-related, and psychological factors linked to mRNA and viral vector COVID-19 vaccines. Statistically significant higher VH (30.4%) and vaccine resistance (12.2%) rates were found for viral vector than mRNA COVID-19 vaccines (7.2% and 1.0%, respectively; p < 0.001). Factors related to viral vector VH were partially different from those related to mRNA VH. Students with greater endorsement on conspiracy statements and negative attitudes toward the vaccine had higher odds of being vaccine-hesitant or -resistant. Students who had received a previous COVID-19 test and who scored higher on the agreeableness personality dimension had lower odds to be vaccine-hesitant or -resistant. The willingness to choose the vaccine was related to the viral vector but not to the mRNA VH. Taking into consideration the factors involved in vaccine hesitancy/resistance in college students could represent a key public health strategy to increase vaccine coverage and reduce viral spreading.

Environmental Risk Assessment of Recombinant Viral Vector Vaccines against SARS-Cov-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the coronavirus disease 2019 (COVID-19) pandemic. Over the past months, considerable efforts have been put into developing effective and safe drugs and vaccines against SARS-CoV-2. Various platforms are being used for the development of COVID-19 vaccine candidates: recombinant viral vectors, protein-based vaccines, nucleic acid-based vaccines, and inactivated/attenuated virus. Recombinant viral vector vaccine candidates represent a significant part of those vaccine candidates in clinical development, with two already authorised for use in the European Union and one currently under rolling review by the European Medicines Agency (EMA). Since recombinant viral vector vaccine candidates are considered as genetically modified organisms (GMOs), their regulatory oversight includes besides an assessment of their quality, safety and efficacy, also an environmental risk assessment (ERA). The present article highlights the main characteristics of recombinant viral vector vaccine (candidates) against SARS-CoV-2 in the pipeline and discusses their features from an environmental risk point of view.