Vaccine Development Process Research Articles

Current Update on Rotavirus in-Silico Multiepitope Vaccine Design.

Rotavirus gastroenteritis is one of the leading causes of pediatric morbidity and mortality worldwide in infants and under-five populations. The World Health Organization (WHO) recommended global incorporation of the rotavirus vaccine in national immunization programs to alleviate the burden of the disease. Implementation of the rotavirus vaccination in certain regions of the world brought about a significant and consistent reduction of rotavirus-associated hospitalizations. However, the efficacy of licensed vaccines remains suboptimal in low-income countries where the incidences of rotavirus gastroenteritis continue to happen unabated. The problem of low efficacy of currently licensed oral rotavirus vaccines in low-income countries necessitates continuous exploration, design, and development of new rotavirus vaccines. Traditional vaccine development is a complex, expensive, labor-intensive, and time-consuming process. Reverse vaccinology essentially utilizes the genome and proteome information on pathogens and has opened new avenues for in-silico multiepitope vaccine design for a plethora of pathogens, promising time reduction in the complete vaccine development pipeline by complementing the traditional vaccinology approach. A substantial number of reviews on licensed rotavirus vaccines and those under evaluation are already available in the literature. However, a collective account of rotavirus in-silico vaccines is lacking in the literature, and such an account may further fuel the interest of researchers to use reverse vaccinology to expedite the vaccine development process. Therefore, the main focus of this review is to summarize the research endeavors undertaken for the design and development of rotavirus vaccines by the reverse vaccinology approach utilizing the tools of immunoinformatics.

Vaccinomics to design a multi-epitope-based vaccine against monkeypox virus using surface-associated proteins

In 2022, the ongoing multi-country outbreak of monkeypox virus—now occurring outside Africa, too is a global health concern. Monkeypox is a zoonotic virus, which causes disease mainly in animals, and then it is transferred to humans. Recently, in the monkeypox epidemic, a large number of human cases emerged while the global health community worked to tackle the outbreak and save lives. Herein, a multi-epitope-based vaccine is designed against monkeypox virus using two surface-associated proteins: MPXVgp002 accession number > YP_010377003.1 and MPXVgp008 accession number > YP_010377007.1 proteins. These proteins were utilized for B- and T-cell epitopes prediction. The epitopes were further screened, and the screen filtered KCKDNEYRSR, RSCNTTHNR, and RTRRETGAS with the antigenicity scores of 0.5279, 0.5604, and 0.7628, respectively. Overall, the epitopes can induce immunity in 99.74% population of the world. Further, GPGPG linkers were used for joining the epitopes and EAAAK linker was used for adjuvant attachment. It has a three-dimensional structure modelled for retaining the structural stability. Three pairs of amino acid residues that were able to make disulfide bonds were chosen: Gly1-Ser82, Cys7-Tyr10, and Phe51-Ile55. Molecular docking of vaccine was done with toll-like receptors, viz., 2, 3, 4, and 8 immune cell receptors. The docking results revealed that the vaccine as potential molecule due to its better binding affinity with toll-like receptors 2, 3, 4 and 8. Top complex in docking in with each receptor was selected based on lowest energy scores— −888.7 kcal/mol (TLR-2), −976.3 kcal/mol (TLR-3), −801.9 kcal/mol (TLR-4), and −955.4 kcal/mol (TLR-4)—were subjected to simulation. The docked complexes were evaluated in 500 ns of MD simulation. Throughout the simulation time, no significant deviation occurred. This confirmed that the vaccine as potential vaccine candidate to interact with immune cell receptors. This interaction is important for the immune system activation. In conclusion, the proposed vaccine construct against monkeypox could induce an effective immune response and speed up the vaccine development process. However, the study is completely based on the computational approach, hence, the experimental validation is required. Communicated by Ramaswamy H. Sarma

Nucleic Acid Vaccines against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) has spread worldwide and imposed a substantial burden on human health, the environment, and socioeconomic development, which has also accelerated the process of nucleic acid vaccine development and licensure. Nucleic acid vaccines are viral genetic sequence-based vaccines and third-generation vaccines after whole virus vaccines and recombinant subunit vaccines, including DNA vaccines and RNA vaccines. They have many unique advantages, but there are many aspects that require optimization. Therefore, the purpose of this review is to discuss the research and development processes of nucleic acid vaccines, summarize the advantages and shortcomings, and propose further optimization strategies by taking COVID-19 vaccines as an example. Hopefully, this work can make a modest contribution in promoting the construction of emergency nucleic acid vaccine platforms and in avoiding the reemergence of similar public health emergencies.

COVID-19 drugs: potential interaction with ATP-binding cassette transporters P-glycoprotein and breast cancer resistance protein.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2, has resulted in acute respiratory distress, fatal systemic manifestations (extrapulmonary as well as pulmonary), and premature mortality among many patients. Therapy for COVID-19 has focused on the treatment of symptoms and of acute inflammation (cytokine storm) and the prevention of viral infection. Although the mechanism of COVID-19 is not fully understood, potential clinical targets have been identified for pharmacological, immunological, and vaccinal approaches.Area coveredPharmacological approaches including drug repositioning have been a priority for initial COVID-19 therapy due to the time-consuming nature of the vaccine development process. COVID-19 drugs have been shown to manage the antiviral infection cycle (cell entry and replication of proteins and genomic RNA) and anti-inflammation. In this review, we evaluated the interaction of current COVID-19 drugs with two ATP-binding cassette transporters [P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP)] and potential drug-drug interactions (DDIs) among COVID-19 drugs, especially those associated with P-gp and BCRP efflux transporters.Expert opinionOverall, understanding the pharmacodynamic/pharmacokinetic DDIs of COVID-19 drugs can be useful for pharmacological therapy in COVID-19 patients.

Pediatric healthcare professionals' opinions, attitudes, and vaccine hesitancy toward personal and children’s COVID-19 vaccination

Background/Aim: Pediatric healthcare professionals are at the forefront of both facilitating an increase vaccine acceptability and reduction in vaccine hesitancy and play a vital role in eliminating vaccine hesitancy of families. In this context, it was thought that the individual pediatric healthcare professional’s vaccine hesitancy could affect successful administration of the coronavirus 2019 (COVID-19) vaccination. This study aimed to determine the opinions and attitudes of pediatricians and pediatric nurses toward the COVID-19 vaccination and the reasons for vaccine hesitancy. The study also aimed to identify their views and attitudes toward COVID-19 vaccination in children. Methods: The survey was carried out as a cross-sectional study between February and May 2021. The study sample consisted of 83 pediatricians and 79 pediatric nurses. Necessary permission was obtained before the study began. Data were collected using questionnaires that had been prepared by researchers. Data were analyzed using descriptive statistical methods and a chi-squared test. Results: Almost all pediatricians and more than half of the pediatric nurses reported that they considered getting vaccinated/were vaccinated; however, a greater proportion of nurses were vaccine-hesitant (P = 0.001). Reasons for not being vaccinated/being hesitant among healthcare professionals included harmful ingredients in the COVID-19 vaccines, thinking that vaccines were developed too quickly, vaccine development studies in different phases did not yield conclusive outcomes, hearing from the social media that vaccines are harmful, believing it is not necessary to receive a vaccine that is not included in the routine immunization schedule, and lack of knowledge about vaccines. The majority of the physicians and nurses who participated in the study reported that, if COVID-19 vaccines were available for children, they would not consider advising it or were unsure (P = 0.003). When asked about the reasons for hesitancy, a greater proportion of nurses reported they thought that vaccines had been developed too quickly (P < 0.001) and that the outcomes of vaccine development studies in different phases were not conclusive (P = 0.008). Conclusion: Healthcare workers serve as role models for vaccination acceptance in the community. Identifying the reasons for vaccine hesitancy among healthcare professionals is key to encouraging vulnerable populations to accept and take the vaccine. Vaccine hesitancy may be countered by comprehensive in-service trainings on vaccine development processes and phases of trials relating to COVID-19 vaccines.

UNDERSTANDING VACCINE ACCEPTANCE AND HESITANCY AMONG THE ROMANIAN POPULATION: INSIGHTS INTO COVID-19 VACCINATION

The advent of COVID-19 vaccines brought hope in combating the global pandemic. However, their acceptance and uptake have faced significant challenges due to vaccine hesitancy and concerns regarding adverse reactions. Various factors influencing vaccine hesitancy, such as fear of side effects, lack of trust in vaccine development processes, misinformation, and socio-cultural beliefs, are discussed. Understanding the reasons behind vaccine hesitancy is crucial in formulating effective strategies to address public concerns. This article aims to explore the factors contributing to vaccine hesitancy and examine the reported adverse reactions following COVID-19 vaccination. By fostering trust, providing accurate information, and establishing robust surveillance systems, public health officials can combat hesitancy and enhance vaccination rates. Efforts must be made to educate individuals about the benefits of vaccination while maintaining transparency regarding potential risks, ultimately paving the way for widespread immunization and mitigating the impact of the ongoing COVID-19 pandemic. Based on our study findings, it is evident that the population of Romania has exhibited a lack of positive response towards the vaccination campaign aimed at curbing the transmission of COVID-19. These results strongly indicate that Romania will face significant challenges in achieving the World Health Organization's recommended vaccination threshold of at least 70% coverage.

COVID-19 Vaccine-Induced Pro-thrombotic Immune Thrombocytopenia (VIPIT): State of the Art.

In 2020, as the severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) pandemic spread rapidly throughout the world, scientists worked relentlessly to develop and test the safety and effectiveness of potential vaccines. Usually, the vaccine development process involves years of investigation and testing prior to gaining approval for use in practice. A pathogenic PF4-dependent syndrome, unrelated to the use of heparin therapy, may be manifested following the administration of viral vector vaccines. It leads to severe clot formation at unusual sites approximately in 1 out of 110.000 vaccinated persons. This side effect, although rare, represents a newly devastating clotting phenomenon manifested in otherwise healthy young adults, who are often female. An in-depth description of the specific biological mechanisms implicated in the syndrome is here summarized.

Communicating about COVID-19 vaccine development and safety.

PurposeBeliefs that the risks from a COVID-19 vaccine outweigh the risks from getting COVID-19 and concerns that the vaccine development process was rushed and lacking rigor have been identified as important drivers of hesitancy and refusal to get a COVID-19 vaccine. We tested whether messages designed to address these beliefs and concerns might promote intentions to get a COVID-19 vaccine.MethodWe conducted an online survey fielded between March 8–23, 2021 with US Veteran (n = 688) and non-Veteran (n = 387) respondents. In a between-subjects experiment, respondents were randomly assigned to a control group (with no message) or to read one of two intervention messages: 1. a fact-box styled message comparing the risks of getting COVID-19 compared to the vaccine, and 2. a timeline styled message describing the development process of the COVID-19 mRNA vaccines.ResultsMost respondents (60%) wanted a COVID-19 vaccine. However, 17% expressed hesitancy and 23% did not want to get a COVID-19 vaccine. The fact-box styled message and the timeline message did not significantly improve vaccination intentions, F(2,358) = 0.86, p = .425, = .005, or reduce the time respondents wanted to wait before getting vaccinated, F(2,306) = 0.79, p = .453, = .005, compared to no messages.DiscussionIn this experimental study, we did not find that providing messages about vaccine risks and the development process had an impact on respondents’ vaccine intentions. Further research is needed to identify how to effectively address concerns about the risks associated with COVID-19 vaccines and the development process and to understand additional factors that influence vaccine intentions.

COVID-19 Vaccination Intent and Belief that Vaccination Will End the Pandemic.

High vaccination coverage is considered to be key in dealing with the coronavirus disease (COVID-19) pandemic. However, vaccine hesitancy can limit uptake. We examined the specific coronavirus beliefs that persons have regarding COVID-19 and COVID-19 vaccines and to what extent these beliefs explain COVID-19 vaccination intentions. We conducted a survey among 4,033 residents of the Netherlands that examined COVID-19 vaccination intentions and various beliefs. Random forest regression analysis explained 76% of the variance in vaccination intentions. The strongest determinant in the model was the belief the COVID-19 crisis will only end if many persons get vaccinated. Other strong determinants were beliefs about safety of vaccines, specifically in relation to vaccine development and approval process; (social) benefits of vaccination; social norms regarding vaccination behavior; and effectiveness of vaccines. We propose to address these specific beliefs in communications about COVID-19 vaccinations to stimulate vaccine uptake.

Progress in COVID research and developments during pandemic.

The pandemic respiratory disease COVID‐19 has spread over the globe within a small span of time. Generally, there are two important points are being highlighted and considered towards the successful diagnosis and treatment process. The first point includes the reduction of the rate of infections and the next one is the decrease of the death rate. The major threat to public health globally progresses due to the absence of effective medication and widely accepted immunization for the COVID‐19. Whereas, understanding of host susceptibility, clinical features, adaptation of COVID‐19 to new environments, asymptomatic infection is difficult and challenging. Therefore, a rapid and an exact determination of pathogenic viruses play an important role in deciding treatments and preventing pandemic to save the people's lives. It is urgent to fix a standardized diagnostic approach for detecting the COVID‐19. Here, this systematic review describes all the current approaches using for screening and diagnosing the COVID‐19 infectious patient. The renaissance in pathogen due to host adaptability and new region, facing creates several obstacles in diagnosis, drug, and vaccine development process. The study shows that adaptation of accurate and affordable diagnostic tools based on candidate biomarkers using sensor and digital medicine technology can deliver effective diagnosis services at the mass level. Better prospects of public health management rely on diagnosis with high specificity and cost‐effective manner along with multidisciplinary research, specific policy, and technology adaptation. The proposed healthcare model with defined road map represents effective prognosis system.

Piezoelectric point-of-care biosensor for the detection of SARS-COV-2 (COVID-19) antibodies

It is always challenging to diagnose a disease using a biosensor reliably, and quickly with high sensitivity and selectivity, simultaneosuly. Recently the world experienced a global pandemic caused by a novel coronavirus (COVID-19). Although the vaccines are available, COVID-19 resulted a huge threat to the entire world with high mortality rates. Irrespective of a specific disease, there is a constant need for a cheaper and faster in-vitro, lab-on-a-chip sensor with high sensitivity and selectivity. Such sensors will not only facilitate the disease detection but will expedite and vaccine development process through detection of its corresponding antibodies when developed. In this article, we present an ultrasonic guided wave sensor using 128° YX lithium niobate piezoelectric wafer, specially designed in a shape of a multi-threaded comb with cantilever beams which is equally selective and sensitive for the detection of corresponding antigen-antibody assays. As a proof of concept in this article, the diagnostic sensor is created and tested for detection of SARS-COV-2 antibodies. Sensors were functionalized with SARS-COV-2 antigens and target antibody for the same was detected. Unique and judicially tuned acoustic features are analyzed for successful detection of the right antibodies. The proposed lab-on-a-chip device utilizes a wide range of diagnostic frequencies resulting into a highly sensitive platform for the diagnostics even to the slightest biophysical changes. The proposed sensor is also believed to extend to the detection of various other antigens/antibodies of different diseases in the future.

COVID-19 Vaccination Status and Concerns Among People Who Use Drugs in Oregon.

The objective of this study was to examine COVID-19 vaccination acceptance and explore reasons for COVID-19 vaccine hesitancy among people who use drugs (PWUDs), a population with increased COVID-19 transmission and morbidity. We conducted semi-structured in-depth interviews with PWUDs in 7 Oregon counties from May 11 to June 25, 2021. Participants (n = 34) were recruited in partnership with syringe service programs and local community organizations staff, participant-referrals, and flyer advertising. Research staff conducted interviews via telephone to assess participants' acceptance of the COVID-19 vaccine, find knowledge gaps where new educational information about vaccination would be helpful, and identify who would be perceived as a trustworthy source of information. Interviews were transcribed and coded using thematic analysis with a deductive approach. Most participants had not received the COVID-19 vaccine and were not planning on or were unsure about receiving it. Participants were mistrustful of the rapid COVID-19 vaccine development process, the agencies involved in the development, and vaccines in general. Participants shared varied and contrasting responses about who they would trust to provide information about the COVID-19 vaccine, including peer recovery support specialists, doctors, or other health care professionals, and specified federal agencies or media outlets. As addiction medicine and public health staff continue to respond to the evolving impacts of COVID-19, vaccination planning should be tailored to the unique needs of PWUD to increase COVID-19 vaccine acceptance in this high-risk population.

Research on the Adjustment of Patent Protection Standards under Emergencies: Based on the TRIPs Agreement

The patent system has a catalytic effect on innovation and imports, which could go some way to alleviating the current vaccine dilemma in the pandemic environment, i.e. insufficient capacity and inequitable distribution. This paper identifies this role through a review of the patent system and the TRIPs Agreement and argues that countries have the flexibility to adapt their patent systems to the current situation through the flexibility provisions of the TRIPs Agreement to maximize this facilitative role in addressing the vaccine issue. This paper suggests that in the current pandemic environment it is necessary to stimulate pharmaceutical companies to accelerate the process of vaccine development by reducing the inventive step testing requirements. In addition, to reduce market risk and maximize the extent to which patents can facilitate the vaccine development process, this paper argues that flexibility should not be used as an excuse for adjusting the duration of protection and requiring a complete patent waiver.

Corona L. So, what have we learned?

Corona L. So, what have we learned?

COVID-19 Vaccination in Pregnancy

COVID-19 pandemic has affected human lives globally. The most important measure to control this pandemic is vaccination and to follow public health measures like wearing facemasks, maintaining social distancing, and hygiene. Over the last one-year, numerous vaccines have been formulated under rigorous regulatory rules globally. During the process of vaccine development, antenatal and breastfeeding women were not included in vaccine research trials, even though they were at increased risk of developing severe COVID-19 infection in comparison to non-pregnant women. There is reassuring data that there are no safety concerns in antenatal patients who received mRNA vaccine in the third trimester and no evidence of increased miscarriage rate if taken at less than 20 weeks of pregnancy. In mRNA vaccine immunized pregnant women, antibodies were found in cord blood. The healthcare staff should provide effective counselling and promote immunization in antenatal women in all trimesters and breastfeeding mothers.

The Role of Influential Actors in Fostering the Polarized COVID-19 Vaccine Discourse on Twitter: Mixed Methods of Machine Learning and Inductive Coding.

BackgroundSince COVID-19 vaccines became broadly available to the adult population, sharp divergences in uptake have emerged along partisan lines. Researchers have indicated a polarized social media presence contributing to the spread of mis- or disinformation as being responsible for these growing partisan gaps in uptake.ObjectiveThe major aim of this study was to investigate the role of influential actors in the context of the community structures and discourse related to COVID-19 vaccine conversations on Twitter that emerged prior to the vaccine rollout to the general population and discuss implications for vaccine promotion and policy.MethodsWe collected tweets on COVID-19 between July 1, 2020, and July 31, 2020, a time when attitudes toward the vaccines were forming but before the vaccines were widely available to the public. Using network analysis, we identified different naturally emerging Twitter communities based on their internal information sharing. A PageRank algorithm was used to quantitively measure the level of “influentialness” of Twitter accounts and identifying the “influencers,” followed by coding them into different actor categories. Inductive coding was conducted to describe discourses shared in each of the 7 communities.ResultsTwitter vaccine conversations were highly polarized, with different actors occupying separate “clusters.” The antivaccine cluster was the most densely connected group. Among the 100 most influential actors, medical experts were outnumbered both by partisan actors and by activist vaccine skeptics or conspiracy theorists. Scientists and medical actors were largely absent from the conservative network, and antivaccine sentiment was especially salient among actors on the political right. Conversations related to COVID-19 vaccines were highly polarized along partisan lines, with “trust” in vaccines being manipulated to the political advantage of partisan actors.ConclusionsThese findings are informative for designing improved vaccine information communication strategies to be delivered on social media especially by incorporating influential actors. Although polarization and echo chamber effect are not new in political conversations in social media, it was concerning to observe these in health conversations on COVID-19 vaccines during the vaccine development process.

Research Advances for Virus-vectored Tuberculosis Vaccines and Latest Findings on Tuberculosis Vaccine Development.

Tuberculosis (TB), caused by respiratory infection with Mycobacterium tuberculosis, remains a major global health threat. The only licensed TB vaccine, the one-hundred-year-old Bacille Calmette-Guérin has variable efficacy and often provides poor protection against adult pulmonary TB, the transmissible form of the disease. Thus, the lack of an optimal TB vaccine is one of the key barriers to TB control. Recently, the development of highly efficacious COVID-19 vaccines within one year accelerated the vaccine development process in human use, with the notable example of mRNA vaccines and adenovirus-vectored vaccines, and increased the public acceptance of the concept of the controlled human challenge model. In the TB vaccine field, recent progress also facilitated the deployment of an effective TB vaccine. In this review, we provide an update on the current virus-vectored TB vaccine pipeline and summarize the latest findings that might facilitate TB vaccine development. In detail, on the one hand, we provide a systematic literature review of the virus-vectored TB vaccines are in clinical trials, and other promising candidate vaccines at an earlier stage of development are being evaluated in preclinical animal models. These research sharply increase the likelihood of finding a more effective TB vaccine in the near future. On the other hand, we provide an update on the latest tools and concept that facilitating TB vaccine research development. We propose that a pre-requisite for successful development may be a better understanding of both the lung-resident memory T cell-mediated mucosal immunity and the trained immunity of phagocytic cells. Such knowledge could reveal novel targets and result in the innovative vaccine designs that may be needed for a quantum leap forward in vaccine efficacy. We also summarized the research on controlled human infection and ultra-low-dose aerosol infection murine models, which may provide more realistic assessments of vaccine utility at earlier stages. In addition, we believe that the success in the ongoing efforts to identify correlates of protection would be a game-changer for streamlining the triage of multiple next-generation TB vaccine candidates. Thus, with more advanced knowledge of TB vaccine research, we remain hopeful that a more effective TB vaccine will eventually be developed in the near future.

Operation Warp Speed: A Legal Analysis of the Vaccine Development Process and How We Got Here

Abstract The COVID-19 Pandemic created a need for a vaccine that would need to be rapidly created, tested and approved in order to reduce the pandemic’s tremendous impact on human life and the economy. This article discusses the vaccine development process as well as Operation Warp Speed, the United States plan for emergency vaccine development in a pandemic situation. Written before the approval of the currently available COVID-19 vaccines, this article also discusses the implications of a speedier vaccine development process as well as recommendations to the standard process.

Maternal Attitudes and Intentions About the COVID-19 Vaccine for Children Aged 5-11 Years.

IntroductionThe current study assessed maternal attitudes and intention about the COVID-19 vaccine for children ages 5–11 years since the onset of the Delta variant and examined if the Delta variant changed maternal perceptions about COVID-19 vaccination and COVID-19 precautions for children.MethodParticipants were 821 mothers (mean age = 40.11 years; 84.3% White) from the United States who had at least one child aged 5–11 years old. They were recruited online and completed questionnaires on Qualtrics (Provo, UT) about their youngest children aged 5–11 years.ResultsMost mothers (n = 595; 72.6%) reported they were very likely to have their child vaccinated for COVID-19 once a vaccine is available for children. After controlling for maternal and child factors, maternal trust in the COVID-19 vaccine development and approval process (odds ratio [OR] = 35.07; p < .001) was associated with maternal likelihood of having one's child vaccinated for COVID-19.DiscussionOur findings highlight that one strategy for increasing maternal intent to have one's child vaccinated for COVID-19 may be bolstering maternal trust in the COVID-19 development and approval process.

A review on risk assessment of formulation development and technology transfer of COVID-19 vaccines

BACKGROUND: COVID-19 pandemic situation made the pharmaceutical companies develop the vaccine with different formulations in a short period. OBJECTIVES: The main objective of the review is to focus on different types of vaccine formulations available globally and the importance of technology transfer in vaccine development associated with potential risks. RESULTS: Research on vaccine development led to various types of vaccines, such as Inactivated vaccines, live attenuated vaccines, Ribonucleic acid (RNA) and Deoxyribonucleic acid (DNA) vaccines, viral vector vaccines, and Protein Subunit Vaccines for COVID-19. But the process of vaccine development and technology transfer is lined with various risks and challenges. Through risk assessment, we found some major potential risks involved in product development; this leads to a smoother and more efficient method to develop safe vaccines available for public health. CONCLUSIONS: This review will explain the significance of technology collaboration for the faster development of various formulations of vaccines globally.