Advances In Vaccine Development Research Articles

Advancing vaccine development: Evaluation of a mannose-modified lipid nanoparticle-based candidate for African swine fever p30 mRNA vaccine eliciting robust immune response in mice.

The African swine fever virus (ASFV) continues to pose significant economic and pandemic risks. Consequently, discovering new, efficient vaccines is crucial. Messenger RNA (mRNA) vaccines have emerged as promising candidates, providing minimal risk of insertional mutagenesis, high safety profiles, effectiveness, rapid scalability in production, and cost-effectiveness. In this study, we have developed an ASF p30 mRNA vaccine candidate (mRNA/Man-LNP) employing mannose-modified lipid nanoparticles (LNPs). The mRNA/Man-LNP exhibited effective antigen presentation and facilitated dendritic cells (DCs) maturation. Notably, it elicited strong IgG titers and activated CD4+ and CD8+ T-cells in immunized mice, all while adhering to stringent biosafety standards. This investigation demonstrates that mRNA/Man-LNP can trigger both humoral and cellular immune responses, suggesting its potential as a potent and promising vaccine candidate for controlling African swine fever (ASF).

Harnessing T-Cells for Enhanced Vaccine Development against Viral Infections

Despite significant strides in vaccine research and the availability of vaccines for many infectious diseases, the threat posed by both known and emerging infectious diseases persists. Moreover, breakthrough infections following vaccination remain a concern. Therefore, the development of novel vaccines is imperative. These vaccines must exhibit robust protective efficacy, broad-spectrum coverage, and long-lasting immunity. One promising avenue in vaccine development lies in leveraging T-cells, which play a crucial role in adaptive immunity and regulate immune responses during viral infections. T-cell recognition can target highly variable or conserved viral proteins, and memory T-cells offer the potential for durable immunity. Consequently, T-cell-based vaccines hold promise for advancing vaccine development efforts. This review delves into the latest research advancements in T-cell-based vaccines across various platforms and discusses the associated challenges.

Analysis and Characterization of the Extracellular Vesicles Released in Non-Cancer Diseases Using Matrix-Assisted Laser Desorption Ionization/Mass Spectrometry.

The extracellular vesicles (EVs) released by cells play a crucial role in intercellular communications and interactions. The direct shedding of EVs from the plasma membrane represents a fundamental pathway for the transfer of properties and information between cells. These vesicles are classified based on their origin, biogenesis, size, content, surface markers, and functional features, encompassing a variety of bioactive molecules that reflect the physiological state and cell type of origin. Such molecules include lipids, nucleic acids, and proteins. Research efforts aimed at comprehending EVs, including the development of strategies for their isolation, purification, and characterization, have led to the discovery of new biomarkers. These biomarkers are proving invaluable for diagnosing diseases, monitoring disease progression, understanding treatment responses, especially in oncology, and addressing metabolic, neurological, infectious disorders, as well as advancing vaccine development. Matrix-Assisted Laser Desorption Ionization (MALDI)/Mass Spectrometry (MS) stands out as a leading tool for the analysis and characterization of EVs and their cargo. This technique offers inherent advantages such as a high throughput, minimal sample consumption, rapid and cost-effective analysis, and user-friendly operation. This review is mainly focused on the primary applications of MALDI-time-of-flight (TOF)/MS in the analysis and characterization of extracellular vesicles associated with non-cancerous diseases and pathogens that infect humans, animals, and plants.

Fully automated high-throughput immuno-µPlaque assay for live-attenuated tetravalent dengue vaccine development.

Dengue fever has remained a continuing global medical threat that impacts half of the world's population. Developing a highly effective dengue vaccine, with live-attenuated tetravalent vaccines as leading candidates, remains essential in preventing this disease. For the development of live virus vaccines (LVVs), potency measurements play a vital role in quantifying the active components of vaccine drug substance as well as drug product during various stages of research, development, and post-licensure evaluations. Traditional plaque-based assays are one of the most common potency test methods, but they generally take up to weeks to complete. Less labor and time-intensive potency assays are thus called for to aid in the acceleration of vaccine development, especially for multivalent LVVs. Here, we introduce a fully automated, 96-well format µPlaque assay that has been optimized as a high-throughput tool to evaluate process and formulation development of a live-attenuated tetravalent dengue vaccine. To the best of our knowledge, this is the first report of a miniaturized viral plaque method for dengue with full automation via an integrated robotic system. Compared to the traditional manual plaque assay, this newly developed method substantially reduces testing time by approximately half and allows for the evaluation of over ten times more samples per run. The fully automated workflow, from cell culture to plaque counting, significantly minimizes analyst hands-on time and improves assay repeatability. The study presents a pioneering solution for the rapid measurement of LVV viral titers, offering promising prospects for advancing vaccine development through high-throughput analytics.

Vaccines to Treat Substance Use Disorders: Current Status and Future Directions.

Addiction, particularly in relation to psychostimulants and opioids, persists as a global health crisis with profound social and economic ramifications. Traditional interventions, including medications and behavioral therapies, often encounter limited success due to the chronic and relapsing nature of addictive disorders. Consequently, there is significant interest in the development of innovative therapeutics to counteract the effects of abused substances. In recent years, vaccines have emerged as a novel and promising strategy to tackle addiction. Anti-drug vaccines are designed to stimulate the immune system to produce antibodies that bind to addictive compounds, such as nicotine, cocaine, morphine, methamphetamine, and heroin. These antibodies effectively neutralize the target molecules, preventing them from reaching the brain and eliciting their rewarding effects. By obstructing the rewarding sensations associated with substance use, vaccines aim to reduce cravings and the motivation to engage in drug use. Although anti-drug vaccines hold significant potential, challenges remain in their development and implementation. The reversibility of vaccination and the potential for combining vaccines with other addiction treatments offer promise for improving addiction outcomes. This review provides an overview of anti-drug vaccines, their mechanisms of action, and their potential impact on treatment for substance use disorders. Furthermore, this review summarizes recent advancements in vaccine development for each specific drug, offering insights for the development of more effective and personalized treatments capable of addressing the distinct challenges posed by various abused substances.

Nanotechnology Platform for Advancing Vaccine Development against the COVID-19 Virus.

The COVID-19 pandemic has had a profound impact on societies, public health, healthcare systems, and the world economy. With over 771 million people infected worldwide and a staggering death toll exceeding 6,960,783 as of 4 October 2023 (according to the World Health Organization), the urgency for a solution was paramount. Since the outbreak, the demand for immediate treatment for COVID-19 viral infection, as well as for effective vaccination against this virus, was soaring, which led scientists, pharmaceutical/biotech companies, government health agencies, etc., to think about a treatment strategy that could control and minimize this outbreak as soon as possible. Vaccination emerged as the most effective strategy to combat this infectious disease. For vaccination strategies, any conventional vaccine approach using attenuated live or inactivated/engineered virus, as well as other approaches, typically requires years of research and assessment. However, the urgency of the situation promoted a faster and more effective approach to vaccine development against COVID-19. The role of nanotechnology in designing, manufacturing, boosting, and delivering vaccines to the host to counter this virus was unquestionably valued and assessed. Several nanoformulations are discussed here in terms of their composition, physical properties, credibility, and applications in past vaccine development (as well as the possibility of using those used in previous applications for the generation of the COVID-19 vaccine). Controlling and eliminating the spread of the virus and preventing future recurrence requires a safe, tolerable, and effective vaccine strategy. In this review, we discuss the potential of nanoformulations as the basis for an effective vaccine strategy against COVID-19.

Genomic epidemiology of Streptococcus pneumoniae serotype 16F lineages.

Due to the emergence of non-vaccine serotypes in vaccinated populations, Streptococcus pneumoniae remains a major global health challenge despite advances in vaccine development. Serotype 16F is among the predominant non-vaccine serotypes identified among vaccinated infants in South Africa (SA). To characterize lineages and antimicrobial resistance in 16F isolates obtained from South Africa and place the local findings in a global context, we analysed 10 923 S. pneumoniae carriage isolates obtained from infants recruited as part of a broader SA birth cohort. We inferred serotype, resistance profile for penicillin, chloramphenicol, cotrimoxazole, erythromycin and tetracycline, and global pneumococcal sequence clusters (GPSCs) from genomic data. To ensure global representation, we also included S. pneumoniae carriage and disease isolates from the Global Pneumococcal Sequencing (GPS) project database (n=19 607, collected from 49 countries across 5 continents, 1995-2018, accessed 17 March 2022). Nine per cent (934/10923) of isolates obtained from infants in the Drakenstein community in SA and 2 %(419/19607) of genomes in the GPS dataset were serotype 16F. Serotype 16F isolates were from 28 different lineages of S. pneumoniae, with GPSC33 and GPSC46 having the highest proportion of serotype 16F isolates at 26 % (346/1353) and 53 % (716/1353), respectively. Serotype 16F isolates were identified globally, but most isolates were collected from Africa. GPSC33 was associated with carriage [OR (95 % CI) 0.24 (0.09-0.66); P=0.003], while GPSC46 was associated with disease [OR (95 % CI) 19.9 (2.56-906.50); P=0.0004]. Ten per cent (37/346) and 15 % (53/346) of isolates within GPSC33 had genes associated with resistance to penicillin and co-trimoxazole, respectively, and 18 % (128/716) of isolates within GPSC46 had genes associated with resistance to co-trimoxazole. Resistant isolates formed genetic clusters, which may suggest emerging resistant lineages. Serotype 16F lineages were common in southern Africa. Some of these lineages were associated with disease and resistance to penicillin and cotrimoxazole. We recommend continuous genomic surveillance to determine the long-term impact of serotype 16F lineages on vaccine efficacy and antimicrobial therapy globally. Investing in vaccine strategies that offer protection over a wide range of serotypes/lineages remains essential. This paper contains data hosted by Microreact.

Control strategies for 2.3.4.4 highly pathogenic avian influenza virus - From vaccines to host disease resistance. Proceeding of The First International Avian Influenza Summit, University of Arkansas- October 16-17, 2023"

Avian influenza virus (AIV) is a highly contagious and lethal disease that can have major impacts on the global poultry industry and food supply. While more frequent in Asia and Europe, highly pathogenic avian influenza virus (HPAIV) outbreaks have traditionally been rare in the U.S. However, in recent years, the U.S. has seen an increase in the incidence of HPAIV outbreaks in wild birds and commercial poultry. In 2014/2015 and in 2021/2022, outbreaks of HPAIV subtype H5NX clade 2.3.4.4 resulted in the death and destruction of over 50 million birds, each costing billions of dollars to the U.S. economy. Here, we present a comprehensive overview of control strategies against the 2.3.4.4 HPAI virus, encompassing both vaccination approaches and host-driven disease resistance mechanisms. The first section outlines the advancements in vaccine development tailored specifically for the 2.3.4.4 HPAI subtype. Through a critical analysis of experimental studies and field trials, we discuss the efficacy, safety, and cross-protection capabilities of various vaccine formulations, including inactivated whole-virus vaccines, vector-based platforms, and novel recombinant technologies. Furthermore, this section explores the challenges associated with vaccine design, including strain diversity, antigenic differences, and logistical hurdles in large-scale vaccination campaigns. The second section delves into host-centric strategies aimed at enhancing natural resistance against 2.3.4.4 HPAI virus infections. Because vaccines are not currently approved for use in the U.S., control strategies for HPAIV are dependent on biosecurity and culling of infected flocks. New strategies for HPAIV control based on gene editing of poultry species could offer solutions for disease control. Two different strategies for improving disease resistance to HPAIV are based on enhancing the innate immunity of the bird and targeting the viral RNA genome inside the cell. By harnessing genetic engineering techniques, including CRISPR/Cas-9 or -13, natural resistance to avian influenza can be achieved in poultry. Taken together, we will examine the current basis of control strategies for the 2.3.4.4 HPAI virus, offering insights into the strengths and limitations of both vaccination and novel gene-editing technologies to enhance host disease resistance to HPAI. By expanding our toolbox, this work contributes to the ongoing efforts to mitigate the impact of 2.3.4.4 HPAI on global poultry industries and public health.

Diagnosis, Treatment and Prevention of Pediatric Lyme disease

Lyme disease remains a significant public health challenge in the United States, particularly in the Northeast and Midwest regions, and is likely to increase in the coming years with population growth to suburban areas and warmer weather. Lyme disease is a bacterial infection caused by the spirochete, Borrelia burgdorferi, that is transmitted to humans through deer ticks. The presentation of Lyme disease can involve multiple systems with dermatologic, neurologic, rheumatologic, and cardiac symptoms commonly described. However, there is substantial variation in the presentation of Lyme disease, creating a challenge to diagnosis and treatment. The standard treatment for Lyme disease is administration of antibacterial agents. Although the majority of pediatric patients achieve symptom resolution with treatment, a subset continues to experience fatigue, pain, and psychological disturbances known as post-treatment Lyme disease syndrome. Prevention of Lyme disease largely relies on behavioral measures such as wearing long sleeves and pants and checking for ticks given the absence of an effective vaccine. Prophylactic antibiotic treatment is also highly effective for children who have experienced a Ixodes tick bite, occurring in an endemic region with tick attachment for at least 36 hours. Although Lyme disease disproportionately impacts children, the existing literature primarily focuses on its presentation in adults. In this review, we summarize the latest literature surrounding the diagnosis, treatment, and prevention of Lyme disease with a specific emphasis on pediatric populations and the recent advancements in vaccine development.

Meta-Analysis of COVID-19 Metabolomics Identifies Variations in Robustness of Biomarkers.

The global COVID-19 pandemic resulted in widespread harms but also rapid advances in vaccine development, diagnostic testing, and treatment. As the disease moves to endemic status, the need to identify characteristic biomarkers of the disease for diagnostics or therapeutics has lessened, but lessons can still be learned to inform biomarker research in dealing with future pathogens. In this work, we test five sets of research-derived biomarkers against an independent targeted and quantitative Liquid Chromatography-Mass Spectrometry metabolomics dataset to evaluate how robustly these proposed panels would distinguish between COVID-19-positive and negative patients in a hospital setting. We further evaluate a crowdsourced panel comprising the COVID-19 metabolomics biomarkers most commonly mentioned in the literature between 2020 and 2023. The best-performing panel in the independent dataset-measured by F1 score (0.76) and AUROC (0.77)-included nine biomarkers: lactic acid, glutamate, aspartate, phenylalanine, β-alanine, ornithine, arachidonic acid, choline, and hypoxanthine. Panels comprising fewer metabolites performed less well, showing weaker statistical significance in the independent cohort than originally reported in their respective discovery studies. Whilst the studies reviewed here were small and may be subject to confounders, it is desirable that biomarker panels be resilient across cohorts if they are to find use in the clinic, highlighting the importance of assessing the robustness and reproducibility of metabolomics analyses in independent populations.

Structure guided mimicry of an essential P. falciparum receptor-ligand complex enhances cross neutralizing antibodies

Invasion of human erythrocytes by Plasmodium falciparum (Pf) merozoites relies on the interaction between two parasite proteins: apical membrane antigen 1 (AMA1) and rhoptry neck protein 2 (RON2). While antibodies to AMA1 provide limited protection against Pf in non-human primate malaria models, clinical trials using recombinant AMA1 alone (apoAMA1) yielded no protection due to insufficient functional antibodies. Immunization with AMA1 bound to RON2L, a 49-amino acid peptide from its ligand RON2, has shown superior protection by increasing the proportion of neutralizing antibodies. However, this approach relies on the formation of a complex in solution between the two vaccine components. To advance vaccine development, here we engineered chimeric antigens by replacing the AMA1 DII loop, displaced upon ligand binding, with RON2L. Structural analysis confirmed that the fusion chimera (Fusion-FD12) closely mimics the binary AMA1-RON2L complex. Immunization studies in female rats demonstrated that Fusion-FD12 immune sera, but not purified IgG, neutralized vaccine-type parasites more efficiently compared to apoAMA1, despite lower overall anti-AMA1 titers. Interestingly, Fusion-FD12 immunization enhanced antibodies targeting conserved epitopes on AMA1, leading to increased neutralization of non-vaccine type parasites. Identifying these cross-neutralizing antibody epitopes holds promise for developing an effective, strain-transcending malaria vaccine.

Crimean-Congo Hemorrhagic Fever Virus: Progress in Vaccine Development.

Crimean-Congo hemorrhagic fever virus (CCHFV), a member of the Nairoviridae family and Bunyavirales order, is transmitted to humans via tick bites or contact with the blood of infected animals. It can cause severe symptoms, including hemorrhagic fever, with a mortality rate between 5 to 30%. CCHFV is classified as a high-priority pathogen by the World Health Organization (WHO) due to its high fatality rate and the absence of effective medical countermeasures. CCHFV is endemic in several regions across the world, including Africa, Europe, the Middle East, and Asia, and has the potential for global spread. The emergence of the disease in new areas, as well as the presence of the tick vector in countries without reported cases, emphasizes the need for preventive measures to be taken. In the past, the lack of a suitable animal model susceptible to CCHFV infection has been a major obstacle in the development of vaccines and treatments. However, recent advances in biotechnology and the availability of suitable animal models have significantly expedited the development of vaccines against CCHF. These advancements have not only contributed to an enhanced understanding of the pathogenesis of CCHF but have also facilitated the evaluation of potential vaccine candidates. This review outlines the immune response to CCHFV and animal models utilized for the study of CCHFV and highlights the progress made in CCHFV vaccine studies. Despite remarkable advancements in vaccine development for CCHFV, it remains crucial to prioritize continued research, collaboration, and investment in this field.

A Continuing Global Threat of a Neglected Tropical Disease: Dengue

Dengue fever is one of the most important mosquito borne neglected tropical disease of major public health concern. The disease may be asymptomatic or may give rise to undifferentiated fever, dengue fever, dengue haemorrhagic fever, or dengue shock syndrome. This review outlines the current knowledge of the dengue virus, mosquito vector, transmission, immune pathogenesis, clinical manifestations, diagnosis, and the treatment and management and prevention and control of these infections and recent advances in vaccine development.

Assessing the Integration of AI Technologies in Enhancing Patient Care Delivery in U.S. Hospitals

The healthcare industry's integration of artificial intelligence (AI) has been significantly accelerated by the COVID-19 pandemic. The urgency for swift diagnosis and treatment, coupled with the rise in demand for remote care and monitoring, has prompted a concentrated effort towards AI-driven solutions aimed at enhancing healthcare delivery and patient outcomes. Various AI-powered technologies including predictive analytics, natural language processing, and computer vision have been harnessed to facilitate screening and diagnosis, expedite drug discovery, and advance vaccine development. Furthermore, AI-driven chatbots and virtual assistants have been deployed for patient triage and remote care provision. While the incorporation of AI in healthcare has yielded substantial benefits, it also poses inherent challenges. This paper delves into the adoption, advantages, and obstacles of AI in the healthcare sector, illuminating AI's potential to revolutionize healthcare delivery while emphasizing the imperative of conscientious implementation and ethical considerations. Additionally, this study presents five case studies of leading U.S. hospitals leveraging AI for various purposes.

Megalocytivirus and Other Members of the Family Iridoviridae in Finfish: A Review of the Etiology, Epidemiology, Diagnosis, Prevention and Control.

Aquaculture has expanded to become the fastest growing food-producing sector in the world. However, its expansion has come under threat due to an increase in diseases caused by pathogens such as iridoviruses commonly found in aquatic environments used for fish farming. Of the seven members belonging to the family Iridoviridae, the three genera causing diseases in fish comprise ranaviruses, lymphocystiviruses and megalocytiviruses. These three genera are serious impediments to the expansion of global aquaculture because of their tropism for a wide range of farmed-fish species in which they cause high mortality. As economic losses caused by these iridoviruses in aquaculture continue to rise, the urgent need for effective control strategies increases. As a consequence, these viruses have attracted a lot of research interest in recent years. The functional role of some of the genes that form the structure of iridoviruses has not been elucidated. There is a lack of information on the predisposing factors leading to iridovirus infections in fish, an absence of information on the risk factors leading to disease outbreaks, and a lack of data on the chemical and physical properties of iridoviruses needed for the implementation of biosecurity control measures. Thus, the synopsis put forth herein provides an update of knowledge gathered from studies carried out so far aimed at addressing the aforesaid informational gaps. In summary, this review provides an update on the etiology of different iridoviruses infecting finfish and epidemiological factors leading to the occurrence of disease outbreaks. In addition, the review provides an update on the cell lines developed for virus isolation and culture, the diagnostic tools used for virus detection and characterization, the current advances in vaccine development and the use of biosecurity in the control of iridoviruses in aquaculture. Overall, we envision that the information put forth in this review will contribute to developing effective control strategies against iridovirus infections in aquaculture.

Plant-Produced Nanoparticles Based on Artificial Self-Assembling Peptide Bearing the Influenza M2e Epitope.

Despite advances in vaccine development, influenza remains a persistent global health threat and the search for a broad-spectrum recombinant vaccine against influenza continues. The extracellular domain of the transmembrane protein M2 (M2e) of the influenza A virus is highly conserved and can be used to develop a universal vaccine. M2e is a poor immunogen by itself, but it becomes highly immunogenic when linked to an appropriate carrier. Here, we report the transient expression of a recombinant protein comprising four tandem copies of M2e fused to an artificial self-assembling peptide (SAP) in plants. The hybrid protein was efficiently expressed in Nicotiana benthamiana using the self-replicating potato virus X-based vector pEff. The protein was purified using metal affinity chromatography under denaturing conditions. The hybrid protein was capable of self-assembly in vitro into spherical particles 15-30 nm in size. The subcutaneous immunization of mice with M2e-carrying nanoparticles induced high levels of M2e-specific IgG antibodies in serum and mucosal secretions. Immunization provided mice with protection against a lethal influenza A virus challenge. SAP-based nanoparticles displaying M2e peptides can be further used to develop a recombinant "universal" vaccine against influenza A produced in plants.

Bacterial Pathogenesis in Various Fish Diseases: Recent Advances and Specific Challenges in Vaccine Development.

Aquaculture is a fast-growing food sector but is plagued by a plethora of bacterial pathogens that infect fish. The rearing of fish at high population densities in aquaculture facilities makes them highly susceptible to disease outbreaks, which can cause significant economic loss. Thus, immunity development in fish through vaccination against various pathogens of economically important aquaculture species has been extensively studied and has been largely accepted as a reliable method for preventing infections. Vaccination studies in aquaculture systems are strategically associated with the economically and environmentally sustainable management of aquaculture production worldwide. Historically, most licensed fish vaccines have been developed as inactivated pathogens combined with adjuvants and provided via immersion or injection. In comparison, live vaccines can simulate a whole pathogenic illness and elicit a strong immune response, making them better suited for oral or immersion-based therapy methods to control diseases. Advanced approaches in vaccine development involve targeting specific pathogenic components, including the use of recombinant genes and proteins. Vaccines produced using these techniques, some of which are currently commercially available, appear to elicit and promote higher levels of immunity than conventional fish vaccines. These technological advancements are promising for developing sustainable production processes for commercially important aquatic species. In this review, we explore the multitude of studies on fish bacterial pathogens undertaken in the last decade as well as the recent advances in vaccine development for aquaculture.

Going Viral-RSV as the Neglected Adult Respiratory Virus.

Human respiratory syncytial virus (RSV) is increasingly recognized as a significant viral pathogen in adults with acute respiratory illness, particularly in the elderly, the immunocompromised, and those with underlying cardiopulmonary disease. Although long acknowledged as one of the most common causes of upper respiratory tract infections (URI) in children since its discovery in 1956, the true burden of disease in adults is likely significantly under-recognized. The emerging evidence of RSV as a driver of morbidity and mortality in elderly and immunocompromised patients has sparked advances in vaccine development and renewed interest in quantifying the true burden of disease. This review attempts to summarize the findings of the most recent evidence investigating the burden of RSV related disease in adults and to highlight where future research is needed.

Correlates with Vaccine Protective Capacity and COVID-19 Disease Symptoms Identified by Serum Proteomics in Vaccinated Individuals.

In the last two years, the coronavirus disease 19 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a scientific and social challenge worldwide. Vaccines have been the most effective intervention for reducing virus transmission and disease severity. However, genetic virus variants are still circulating among vaccinated individuals with different disease symptomatology. Understanding the protective- or disease-associated mechanisms in vaccinated individuals is relevant to advances in vaccine development and implementation. To address this objective, serum-protein profiles were characterized by quantitative proteomics and data-analysis algorithms in four cohorts of uninfected and SARS-CoV-2-infected vaccinated individuals with asymptomatic, non-severe, and severe disease symptomatology. The results show that immunoglobulins were the most overrepresented proteins in infected cohorts when compared to PCR-negative individuals. The immunoglobulin profile varied between different infected cohorts and correlated with protective- or disease-associated capacity. Overrepresented immunoglobulins in PCR-positive individuals correlated with protective response against SARS-CoV-2, other viruses, and thrombosis in asymptomatic cases. In non-severe cases, correlates of protection against SARS-CoV-2 and HBV together with risk of myasthenia gravis and allergy and autoantibodies were observed. Patients with severe symptoms presented risk for allergy, chronic idiopathic thrombocytopenic purpura, and autoantibodies. The analysis of underrepresented immunoglobulins in PCR-positive compared to PCR-negative individuals identified vaccine-induced protective epitopes in various coronavirus proteins, including the spike receptor-binding domain RBD. Non-immunoglobulin proteins were associated with COVID-19 symptoms and biological processes. These results evidence host-associated differences in response to vaccination and the possibility of improving vaccine efficacy against SARS-CoV-2.

Advances in vaccine development and the immune response against toxoplasmosis in sheep and goats.

Toxoplasmosis is a zoonotic, parasitic infection caused by the intracellular, apicomplexan parasite Toxoplasma gondii, which infects all homeothermic animals including humans. The parasite has a major economic impact on the livestock industry. This is especially true for small ruminants (sheep, goats) as it is one of the most likely reasons for reproductive disorders in these animals. Primary infection in sheep and goats can result in a fetus that is mummified or macerated, fetal embryonic death, abortion, stillbirth, or the postnatal death of neonates, all of which threaten sheep and goat rearing globally. Humans can also become infected by ingesting bradyzoite-containing chevon or mutton, or the contaminated milk of sheep or goats, highlighting the zoonotic significance of this parasite. This article reviews the advances in vaccine development over recent decades and our current understanding of the immune response to toxoplasmosis in small ruminants (sheep, and goats).