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1.
Vaccines (Basel) ; 8(2)2020 Mar 29.
Article in English | MEDLINE | ID: covidwho-1726034

ABSTRACT

In December 2019, the outbreak of pneumonia caused by a novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a serious pandemic in China and other countries worldwide. So far, more than 460,000 confirmed cases were diagnosed in nearly 190 countries, causing globally over 20,000 deaths. Currently, the epidemic is still spreading and there is no effective means to prevent the infection. Vaccines are proved to be the most effective and economical means to prevent and control infectious diseases. Several countries, companies, and institutions announced their programs and progress on vaccine development against the virus. While most of the vaccines are under design and preparation, there are some that have entered efficacy evaluation in animals and initial clinical trials. This review mainly focused on the progress and our prospects on field of vaccine development against SARS-CoV-2.

2.
Front Immunol ; 12: 645210, 2021.
Article in English | MEDLINE | ID: covidwho-1383856

ABSTRACT

Vaccination is one of the most efficient public healthcare measures to fight infectious diseases. Nevertheless, the immune mechanisms induced in vivo by vaccination are still unclear. The route of administration, an important vaccination parameter, can substantially modify the quality of the response. How the route of administration affects the generation and profile of immune responses is of major interest. Here, we aimed to extensively characterize the profiles of the innate and adaptive response to vaccination induced after intradermal, subcutaneous, or intramuscular administration with a modified vaccinia virus Ankara model vaccine in non-human primates. The adaptive response following subcutaneous immunization was clearly different from that following intradermal or intramuscular immunization. The subcutaneous route induced a higher level of neutralizing antibodies than the intradermal and intramuscular vaccination routes. In contrast, polyfunctional CD8+ T-cell responses were preferentially induced after intradermal or intramuscular injection. We observed the same dichotomy when analyzing the early molecular and cellular immune events, highlighting the recruitment of cell populations, such as CD8+ T lymphocytes and myeloid-derived suppressive cells, and the activation of key immunomodulatory gene pathways. These results demonstrate that the quality of the vaccine response induced by an attenuated vaccine is shaped by early and subtle modifications of the innate immune response. In this immunization context, the route of administration must be tailored to the desired type of protective immune response. This will be achieved through systems vaccinology and mathematical modeling, which will be critical for predicting the efficacy of the vaccination route for personalized medicine.


Subject(s)
Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , CD8-Positive T-Lymphocytes/immunology , Myeloid-Derived Suppressor Cells/immunology , Vaccination , Vaccinia virus/immunology , Vaccinia/immunology , Viral Vaccines/pharmacology , Animals , Injections, Intradermal , Injections, Intramuscular , Macaca fascicularis , Male , Vaccines, Attenuated/pharmacology
3.
Vaccine X ; 7: 100084, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1386131

ABSTRACT

BACKGROUND: Infectious diseases continue to cause significant impact on human health. Vaccines are instrumental in preventing infectious diseases and mitigating pandemics and epidemics. SARS-CoV-2 is the most recent example of an urgent pandemic that requires the development of vaccines. This study combined real-world data and geospatial visualization techniques to demonstrate methods to monitor and communicate the uptake and impact of existing and new vaccines. METHODS: Observational data of existing pediatric rotavirus vaccines were used as an example. A large US national insurance claims database was accessed to build an analytic dataset for a 20-year period (1996-2017). For each week and multiple geographic scales, animated spatial and non-spatial visualization techniques were applied to demonstrate changes in seasonal rotavirus epidemic curves and population-based disease rates before, during, and after vaccine introduction in 2006. The geographic scales included national, state, county and zip code tabulation areas. An online web-based digital atlas was built to display either continuous or snapshot visualizations of disease patterns, vaccine uptake, and improved health outcomes after vaccination (http://www.mapvaccines.com). RESULTS: Over 17 million zip code-weeks of data were available for analysis. The animations show geospatial patterns of rotavirus-related medical encounter rates peaking every year from November - February prior to vaccine availability in 2006. Visualizations showed increasing vaccination coverage rates at all geographic scales over time. Declines in medical encounter rates accelerated as vaccination coverage rapidly increased after 2010. The data maps also identified geographic hotspots with low vaccination rates and persistent disease rates. CONCLUSION: This project developed novel web-based methods to communicate location and time-based vaccine uptake and the related reduction in medical visits due to viral infection. Future applications of the visualization could be used by health agencies to monitor known or novel disease patterns over time in conjunction with close assessment of current and future vaccine utilization.

4.
Pharmacy (Basel) ; 9(1)2021 Mar 03.
Article in English | MEDLINE | ID: covidwho-1308394

ABSTRACT

Vaccinations are a safe and effective way to protect against infectious diseases. The World Health Organization estimates vaccines have saved more lives than any other interventions and every year about two to three million deaths are averted worldwide through immunization. To improve vaccination coverage, pharmacists have been increasingly involved in immunization roles in their communities-as advocates, educators, and immunizers. Community pharmacy-based vaccination services have increased both in the number of immunization providers and the number of sites where patients can receive immunizations. In Canada, health care is under provincial legislation-and so, there are distinct differences in scope of pharmacist practice across the country. Prior to the COVID-19 outbreak in early 2020, in Québec, Canada's second-largest province, pharmacists did not have the authority to administer vaccines. To help prepare pharmacists in Québec to become immunizers, we developed and deployed a series of accredited workshops. In these facilitated workshops, pharmacists were able to share best practices that may lead to providing effective vaccination services, identify common competency gaps, discuss effective patient communication skills, and determine how to target the most vulnerable population groups. Participants were also asked to evaluate the workshop. Our results indicate the evaluation was very reliable in measuring participant satisfaction (Cronbach's α = 0.94) and pharmacists commented that the workshops' learning outcomes exceeded their expectations, and the topics covered were relevant and applicable. The evaluation also asked participants to identify weaknesses of training, so future educational interventions can be planned accordingly. We believe this work will contribute to the continual growth and advancement of the pharmacy profession in Canada.

5.
J Med Internet Res ; 23(6): e24435, 2021 06 29.
Article in English | MEDLINE | ID: covidwho-1286902

ABSTRACT

BACKGROUND: Vaccination is a cornerstone of the prevention of communicable infectious diseases; however, vaccines have traditionally met with public fear and hesitancy, and COVID-19 vaccines are no exception. Social media use has been demonstrated to play a role in the low acceptance of vaccines. OBJECTIVE: The aim of this study is to identify the topics and sentiments in the public COVID-19 vaccine-related discussion on social media and discern the salient changes in topics and sentiments over time to better understand the public perceptions, concerns, and emotions that may influence the achievement of herd immunity goals. METHODS: Tweets were downloaded from a large-scale COVID-19 Twitter chatter data set from March 11, 2020, the day the World Health Organization declared COVID-19 a pandemic, to January 31, 2021. We used R software to clean the tweets and retain tweets that contained the keywords vaccination, vaccinations, vaccine, vaccines, immunization, vaccinate, and vaccinated. The final data set included in the analysis consisted of 1,499,421 unique tweets from 583,499 different users. We used R to perform latent Dirichlet allocation for topic modeling as well as sentiment and emotion analysis using the National Research Council of Canada Emotion Lexicon. RESULTS: Topic modeling of tweets related to COVID-19 vaccines yielded 16 topics, which were grouped into 5 overarching themes. Opinions about vaccination (227,840/1,499,421 tweets, 15.2%) was the most tweeted topic and remained a highly discussed topic during the majority of the period of our examination. Vaccine progress around the world became the most discussed topic around August 11, 2020, when Russia approved the world's first COVID-19 vaccine. With the advancement of vaccine administration, the topic of instruction on getting vaccines gradually became more salient and became the most discussed topic after the first week of January 2021. Weekly mean sentiment scores showed that despite fluctuations, the sentiment was increasingly positive in general. Emotion analysis further showed that trust was the most predominant emotion, followed by anticipation, fear, sadness, etc. The trust emotion reached its peak on November 9, 2020, when Pfizer announced that its vaccine is 90% effective. CONCLUSIONS: Public COVID-19 vaccine-related discussion on Twitter was largely driven by major events about COVID-19 vaccines and mirrored the active news topics in mainstream media. The discussion also demonstrated a global perspective. The increasingly positive sentiment around COVID-19 vaccines and the dominant emotion of trust shown in the social media discussion may imply higher acceptance of COVID-19 vaccines compared with previous vaccines.


Subject(s)
COVID-19 Vaccines , COVID-19 , Emotions , Latent Class Analysis , Social Media , Trust , Vaccination/psychology , COVID-19/immunology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19 Vaccines/immunology , Humans , Immunity, Herd , Natural Language Processing , Pandemics , SARS-CoV-2/immunology
6.
Neurol Ther ; 10(2): 523-537, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1274996

ABSTRACT

Guillain-Barré syndrome (GBS) is an autoimmune disorder of the peripheral nervous system that typically develops within 4 weeks after infection. In addition to conventional infectious diseases with which we are familiar, emerging infectious diseases, such as Zika virus infection and coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), have also been suggested to be associated with GBS. GBS is mainly categorized into a demyelinating subtype known as acute inflammatory demyelinating polyneuropathy (AIDP) and an axonal subtype known as acute motor axonal neuropathy (AMAN). Most patients who develop GBS after Zika virus infection or COVID-19 have AIDP. The concept of molecular mimicry between pathogens and human peripheral nerve components was established through studies of AMAN with anti-ganglioside GM1 antibodies occurring after Campylobacter jejuni infection. Although such mimicry between specific pathogens and myelin or Schwann cell components has not been clearly demonstrated in AIDP, a similarity of Zika virus and SARS-CoV-2 proteins to human proteins has been suggested. With the development of global commerce and travel, emerging infectious diseases will continue to threaten public health. From this viewpoint, the development of vaccines and antiviral drugs is important to prepare for and control emerging infectious diseases. Although a decrease in the number of patients after the 2015-2016 Zika epidemic increased the difficulty in conducting phase 3 trials for Zika virus vaccines, the efficacy and safety of new vaccines have recently been demonstrated for COVID-19. In general, vaccines can decrease the risk of infectious disease by stimulating the immune system, and discussions regarding an increased risk of autoimmune disorders, such as GBS, have been ongoing for many years. However, the risk of GBS is not considered a legitimate reason to limit the administration of currently available vaccines, as only a trivial association or no association with GBS has been demonstrated.

7.
Biosci Trends ; 15(3): 188-191, 2021 Jul 06.
Article in English | MEDLINE | ID: covidwho-1271034

ABSTRACT

The COVID-19 pandemic continues to ravage the world. As many countries have entered the postpandemic period, current efforts to prevent and control COVID-19 have gradually been normalized in many countries. Although the focus is on vaccines to achieve herd immunity, conventional physical containment strategies should be reassessed as part of efforts to prevent and control infectious diseases. Continued respiratory protective measures such as social distancing and the wearing of masks have been extensively accepted by the public in most countries. A point worth noticing is that the activities of influenza and other respiratory diseases have decreased as these strategies have been implemented. Public mobilization and large-scale campaigns to promote health are also important to interrupting the transmission of pathogens. A good example can be found in the achievements of China's Patriotic Public Health Campaign. These practices underscore the importance of enhancing physical containment strategies and public mobilization and management, with support from the legal system, to respond to any potential emerging infectious diseases.


Subject(s)
COVID-19/epidemiology , COVID-19/prevention & control , Public Health , SARS-CoV-2/physiology , COVID-19/virology , Humans , Influenza, Human/epidemiology
8.
Hypertens Res ; 44(9): 1047-1053, 2021 09.
Article in English | MEDLINE | ID: covidwho-1260939

ABSTRACT

There is currently a respiratory disease outbreak caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). After rapid development, RNA vaccines and adenoviral vector vaccines were approved within a year, which has demonstrated the strong impact of preventing infectious diseases using gene therapy technology. Furthermore, intensive immunological analysis has been performed to evaluate the efficiency and safety of these vaccines, potentially allowing for rapid progress in vaccine technology. After the coronavirus disease 2019 (COVID-19) era, the novel vaccine technology developed will expand to other vaccines. We have been developing vaccines for chronic diseases, such as hypertension, for >10 years. Regarding the development of vaccines against self-antigens (i.e., angiotensin II), the vaccine should efficiently induce a blocking antibody response against the self-antigen without activating cytotoxic T cells. Therefore, the epitope vaccine approach has been proposed to induce antibody production in response to a combination of a B cell epitope and exogenous T cell epitopes through major histocompatibility complex molecules. When these vaccines are established as therapeutic options for hypertension, their administration regimen, which might be a few times per year, will replace daily medication use. Thus, therapeutic vaccines for hypertension may be a novel option to control the progression of cerebrovascular diseases. Hopefully, the accumulation of immunological findings and vaccine technology advances due to COVID-19 will provide a novel concept for vaccines for chronic diseases.


Subject(s)
Autoantigens/immunology , COVID-19 Vaccines/immunology , COVID-19/prevention & control , Hypertension/therapy , SARS-CoV-2/immunology , Vaccines/therapeutic use , Chronic Disease , Humans
9.
Risk Manag Healthc Policy ; 14: 2011-2019, 2021.
Article in English | MEDLINE | ID: covidwho-1247727

ABSTRACT

After the first wave of the COVID-19 pandemic that began in early 2020 was brought under control, there have been some regional and small-scale cases of new infections in China. In order to prevent the resurgence of the epidemic, the Chinese government has continued the use of effective prevention and control measures in key epidemic areas. New prevention and control measures have also been developed based on the characteristics of the epidemic and the social habits of the Chinese people. The strategies applied in China include large-scale nucleic acid testing, travel health code management, and patient treatment based on a combination of Chinese and Western medicine. These measures can provide a reference point for the global public health system that is facing the pandemic. The article suggests that to prevent a pandemic, we must not only rely on vaccines and drugs, but also need to take actions and apply social measures to manage the risk of infectious diseases.

10.
Proc Natl Acad Sci U S A ; 118(21)2021 05 25.
Article in English | MEDLINE | ID: covidwho-1233774

ABSTRACT

The COVID-19 pandemic triggered an unparalleled pursuit of vaccines to induce specific adaptive immunity, based on virus-neutralizing antibodies and T cell responses. Although several vaccines have been developed just a year after SARS-CoV-2 emerged in late 2019, global deployment will take months or even years. Meanwhile, the virus continues to take a severe toll on human life and exact substantial economic costs. Innate immunity is fundamental to mammalian host defense capacity to combat infections. Innate immune responses, triggered by a family of pattern recognition receptors, induce interferons and other cytokines and activate both myeloid and lymphoid immune cells to provide protection against a wide range of pathogens. Epidemiological and biological evidence suggests that the live-attenuated vaccines (LAV) targeting tuberculosis, measles, and polio induce protective innate immunity by a newly described form of immunological memory termed "trained immunity." An LAV designed to induce adaptive immunity targeting a particular pathogen may also induce innate immunity that mitigates other infectious diseases, including COVID-19, as well as future pandemic threats. Deployment of existing LAVs early in pandemics could complement the development of specific vaccines, bridging the protection gap until specific vaccines arrive. The broad protection induced by LAVs would not be compromised by potential antigenic drift (immune escape) that can render viruses resistant to specific vaccines. LAVs might offer an essential tool to "bend the pandemic curve," averting the exhaustion of public health resources and preventing needless deaths and may also have therapeutic benefits if used for postexposure prophylaxis of disease.


Subject(s)
COVID-19/prevention & control , Immunity, Innate , Pandemics/prevention & control , Vaccines/immunology , Adaptive Immunity , COVID-19/immunology , COVID-19 Vaccines/immunology , Immunity, Heterologous , Immunologic Memory , SARS-CoV-2/immunology , Vaccines, Attenuated/immunology
11.
Vaccines (Basel) ; 9(4)2021 Apr 15.
Article in English | MEDLINE | ID: covidwho-1231516

ABSTRACT

Increases in the world's population and population density promote the spread of emerging pathogens. Vaccines are the most cost-effective means of preventing this spread. Traditional methods used to identify and produce new vaccines are not adequate, in most instances, to ensure global protection. New technologies are urgently needed to expedite large scale vaccine development. mRNA-based vaccines promise to meet this need. mRNA-based vaccines exhibit a number of potential advantages relative to conventional vaccines, namely they (1) involve neither infectious elements nor a risk of stable integration into the host cell genome; (2) generate humoral and cell-mediated immunity; (3) are well-tolerated by healthy individuals; and (4) are less expensive and produced more rapidly by processes that are readily standardized and scaled-up, improving responsiveness to large emerging outbreaks. Multiple mRNA vaccine platforms have demonstrated efficacy in preventing infectious diseases and treating several types of cancers in humans as well as animal models. This review describes the factors that contribute to maximizing the production of effective mRNA vaccine transcripts and delivery systems, and the clinical applications are discussed in detail.

12.
Hum Gene Ther ; 32(11-12): 541-562, 2021 06.
Article in English | MEDLINE | ID: covidwho-1216585

ABSTRACT

Severe acute respiratory syndrome (SARS) is a newly emerging infectious disease (COVID-19) caused by the novel coronavirus SARS-coronavirus 2 (CoV-2). To combat the devastating spread of SARS-CoV-2, extraordinary efforts from numerous laboratories have focused on the development of effective and safe vaccines. Traditional live-attenuated or inactivated viral vaccines are not recommended for immunocompromised patients as the attenuated virus can still cause disease via phenotypic or genotypic reversion. Subunit vaccines require repeated dosing and adjuvant use to be effective, and DNA vaccines exhibit lower immune responses. mRNA vaccines can be highly unstable under physiological conditions. On the contrary, naturally antigenic viral vectors with well-characterized structure and safety profile serve as among the most effective gene carriers to provoke immune response via heterologous gene transfer. Viral vector-based vaccines induce both an effective cellular immune response and a humoral immune response owing to their natural adjuvant properties via transduction of immune cells. Consequently, viral vectored vaccines carrying the SARS-CoV-2 spike protein have recently been generated and successfully used to activate cytotoxic T cells and develop a neutralizing antibody response. Recent progress in SARS-CoV-2 vaccines, with an emphasis on gene therapy viral vector-based vaccine development, is discussed in this review.


Subject(s)
COVID-19 Vaccines/pharmacology , Genetic Vectors , Vaccines, Attenuated/pharmacology , Vaccines, Synthetic/pharmacology , Viral Structural Proteins/chemistry , Adenoviridae/genetics , Genetic Therapy/methods , Genetic Vectors/chemistry , Genetic Vectors/genetics , Humans , Lentivirus/genetics , SARS-CoV-2/genetics , Vaccines, DNA/pharmacology , Viral Structural Proteins/genetics , Viral Structural Proteins/metabolism
13.
FEBS J ; 289(14): 4251-4303, 2022 Jul.
Article in English | MEDLINE | ID: covidwho-1209887

ABSTRACT

Vaccination is one of the greatest achievements in biomedical research preventing death and morbidity in many infectious diseases through the induction of pathogen-specific humoral and cellular immune responses. Currently, no effective vaccines are available for pathogens with a highly variable antigenic load, such as the human immunodeficiency virus or to induce cellular T-cell immunity in the fight against cancer. The recent SARS-CoV-2 outbreak has reinforced the relevance of designing smart therapeutic vaccine modalities to ensure public health. Indeed, academic and private companies have ongoing joint efforts to develop novel vaccine prototypes for this virus. Many pathogens are covered by a dense glycan-coat, which form an attractive target for vaccine development. Moreover, many tumor types are characterized by altered glycosylation profiles that are known as "tumor-associated carbohydrate antigens". Unfortunately, glycans do not provoke a vigorous immune response and generally serve as T-cell-independent antigens, not eliciting protective immunoglobulin G responses nor inducing immunological memory. A close and continuous crosstalk between glycochemists and glycoimmunologists is essential for the successful development of efficient immune modulators. It is clear that this is a key point for the discovery of novel approaches, which could significantly improve our understanding of the immune system. In this review, we discuss the latest advancements in development of vaccines against glycan epitopes to gain selective immune responses and to provide an overview on the role of different immunogenic constructs in improving glycovaccine efficacy.


Subject(s)
COVID-19 , Neoplasms , Vaccines , COVID-19/prevention & control , Glycoconjugates/therapeutic use , Humans , Neoplasms/prevention & control , Polysaccharides/therapeutic use , SARS-CoV-2
14.
Math Biosci ; 337: 108621, 2021 07.
Article in English | MEDLINE | ID: covidwho-1207058

ABSTRACT

When allocating limited vaccines to control an infectious disease, policy makers frequently have goals relating to individual health benefits (e.g., reduced morbidity and mortality) as well as population-level health benefits (e.g., reduced transmission and possible disease eradication). We consider the optimal allocation of a limited supply of a preventive vaccine to control an infectious disease, and four different allocation objectives: minimize new infections, deaths, life years lost, or quality-adjusted life years (QALYs) lost due to death. We consider an SIR model with n interacting populations, and a single allocation of vaccine at time 0. We approximate the model dynamics to develop simple analytical conditions characterizing the optimal vaccine allocation for each objective. We instantiate the model for an epidemic similar to COVID-19 and consider n=2 population groups: one group (individuals under age 65) with high transmission but low mortality and the other group (individuals age 65 or older) with low transmission but high mortality. We find that it is optimal to vaccinate younger individuals to minimize new infections, whereas it is optimal to vaccinate older individuals to minimize deaths, life years lost, or QALYs lost due to death. Numerical simulations show that the allocations resulting from our conditions match those found using much more computationally expensive algorithms such as exhaustive search. Sensitivity analysis on key parameters indicates that the optimal allocation is robust to changes in parameter values. The simple conditions we develop provide a useful means of informing vaccine allocation decisions for communicable diseases.


Subject(s)
Epidemics/prevention & control , Mass Vaccination , Models, Theoretical , Viral Vaccines , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/prevention & control , Humans , Mass Vaccination/methods , Mass Vaccination/standards , Middle Aged , Viral Vaccines/administration & dosage , Viral Vaccines/supply & distribution , Young Adult
15.
Int J Pept Res Ther ; 27(3): 1729-1740, 2021.
Article in English | MEDLINE | ID: covidwho-1188142

ABSTRACT

COVID-19 is an infectious disease caused by a newly discovered corona virus SARS-COV-2. It is the most dangerous epidemic existing currently all over the world. To date, there is no licensed vaccine and not any particular efficient therapeutic agent available to prevent or cure the disease. So development of an effective vaccine is the urgent need of the time. The proposed study aims to identify potential vaccine candidates by screening the complete proteome of SARS-COV-2 using the computational approach. From 14 protein entries in UniProtKB, 4 proteins were screened for epitope prediction based on consensus antigenicity predictions and various physico-chemical criteria like transmembrane domain, allergenicity, GRAVY value, toxicity, stability index. Comprehensive analysis of these 4 antigens revealed that spike protein (P0DTC2) and nucleoprotein (P0DTC9) show the greatest potential for experimental immunogenicity analysis. These 2 proteins have several potential CD4+ and CD8+ T-cell epitopes, as well as high probability of B-cell epitope regions as compared to well-characterized antigen the matrix protein 1 [Influenza A virus (H5N1)]. In addition, the epitope SIIAYTMSL predicted from spike protein (P0DTC2) and epitope SPRWYFYYL predicted from nucleoprotein (P0DTC9) exhibited more than 60% population coverage in the target populations Europe, North America, South Asia, Northeast Asia taken in this study. These epitopes have also been found to exhibit highly significant TCR-pMHC interactions having a joint Z value of 4.51 and 4.37 respectively. Therefore, this analysis suggests that the predicted epitopes might be suitable vaccine candidates and should be subjected to further in-vivo and in-vitro studies.

17.
Allergy ; 76(6): 1640-1660, 2021 06.
Article in English | MEDLINE | ID: covidwho-1165739

ABSTRACT

Vaccines are essential public health tools with a favorable safety profile and prophylactic effectiveness that have historically played significant roles in reducing infectious disease burden in populations, when the majority of individuals are vaccinated. The COVID-19 vaccines are expected to have similar positive impacts on health across the globe. While serious allergic reactions to vaccines are rare, their underlying mechanisms and implications for clinical management should be considered to provide individuals with the safest care possible. In this review, we provide an overview of different types of allergic adverse reactions that can potentially occur after vaccination and individual vaccine components capable of causing the allergic adverse reactions. We present the incidence of allergic adverse reactions during clinical studies and through post-authorization and post-marketing surveillance and provide plausible causes of these reactions based on potential allergenic components present in several common vaccines. Additionally, we review implications for individual diagnosis and management and vaccine manufacturing overall. Finally, we suggest areas for future research.


Subject(s)
COVID-19 , Hypersensitivity , Vaccines , COVID-19 Vaccines , Humans , Hypersensitivity/diagnosis , Hypersensitivity/epidemiology , Hypersensitivity/etiology , Pandemics , SARS-CoV-2 , Vaccines/adverse effects
18.
Vaccine ; 39(16): 2190-2200, 2021 04 15.
Article in English | MEDLINE | ID: covidwho-1152683

ABSTRACT

Vaccines are one of the most important tools in public health and play an important role in infectious diseases control. Owing to its precision, safe profile and flexible manufacturing, mRNA vaccines are reaching the stoplight as a new alternative to conventional vaccines. In fact, mRNA vaccines were the technology of choice for many companies to combat the Covid-19 pandemic, and it was the first technology to be approved in both United States and in Europe Union as a prophylactic treatment. Additionally, mRNA vaccines are being studied in the clinic to treat a number of diseases including cancer, HIV, influenza and even genetic disorders. The increased demand for mRNA vaccines requires a technology platform and cost-effective manufacturing process with a well-defined product characterisation. Large scale production of mRNA vaccines consists in a 1 or 2-step in vitro reaction followed by a purification platform with multiple steps that can include Dnase digestion, precipitation, chromatography or tangential flow filtration. In this review we describe the current state-of-art of mRNA vaccines, focusing on the challenges and bottlenecks of manufacturing that need to be addressed to turn this new vaccination technology into an effective, fast and cost-effective response to emerging health crises.


Subject(s)
RNA, Messenger/administration & dosage , Vaccines, Synthetic , COVID-19 , Humans , Pandemics
20.
Front Immunol ; 12: 598778, 2021.
Article in English | MEDLINE | ID: covidwho-1133909

ABSTRACT

Emerging infectious diseases (EIDs) caused by viruses are increasing in frequency, causing a high disease burden and mortality world-wide. The COVID-19 pandemic caused by the novel SARS-like coronavirus (SARS-CoV-2) underscores the need to innovate and accelerate the development of effective vaccination strategies against EIDs. Human leukocyte antigen (HLA) molecules play a central role in the immune system by determining the peptide repertoire displayed to the T-cell compartment. Genetic polymorphisms of the HLA system thus confer a strong variability in vaccine-induced immune responses and may complicate the selection of vaccine candidates, because the distribution and frequencies of HLA alleles are highly variable among different ethnic groups. Herein, we build on the emerging paradigm of rational epitope-based vaccine design, by describing an immunoinformatics tool (Predivac-3.0) for proteome-wide T-cell epitope discovery that accounts for ethnic-level variations in immune responsiveness. Predivac-3.0 implements both CD8+ and CD4+ T-cell epitope predictions based on HLA allele frequencies retrieved from the Allele Frequency Net Database. The tool was thoroughly assessed, proving comparable performances (AUC ~0.9) against four state-of-the-art pan-specific immunoinformatics methods capable of population-level analysis (NetMHCPan-4.0, Pickpocket, PSSMHCPan and SMM), as well as a strong accuracy on proteome-wide T-cell epitope predictions for HIV-specific immune responses in the Japanese population. The utility of the method was investigated for the COVID-19 pandemic, by performing in silico T-cell epitope mapping of the SARS-CoV-2 spike glycoprotein according to the ethnic context of the countries where the ChAdOx1 vaccine is currently initiating phase III clinical trials. Potentially immunodominant CD8+ and CD4+ T-cell epitopes and population coverages were predicted for each population (the Epitope Discovery mode), along with optimized sets of broadly recognized (promiscuous) T-cell epitopes maximizing coverage in the target populations (the Epitope Optimization mode). Population-specific epitope-rich regions (T-cell epitope clusters) were further predicted in protein antigens based on combined criteria of epitope density and population coverage. Overall, we conclude that Predivac-3.0 holds potential to contribute in the understanding of ethnic-level variations of vaccine-induced immune responsiveness and to guide the development of epitope-based next-generation vaccines against emerging pathogens, whose geographic distributions and populations in need of vaccinations are often well-defined for regional epidemics.


Subject(s)
CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , COVID-19/immunology , Epitopes, T-Lymphocyte/metabolism , HLA Antigens/metabolism , Proteomics/methods , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , COVID-19/epidemiology , COVID-19 Vaccines , Communicable Diseases, Emerging , Epitopes, T-Lymphocyte/genetics , HLA Antigens/genetics , Humans , Immunogenicity, Vaccine , Medical Informatics Applications , Pandemics/prevention & control , Polymorphism, Genetic , Protein Binding , Software , Spike Glycoprotein, Coronavirus/genetics
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