Vaccinia Virus Vectors Research Articles

Efficiency of NHEJ-CRISPR/Cas9 and Cre-LoxP Engineered Recombinant Turkey Herpesvirus Expressing Pasteurella multocida OmpH Protein for Fowl Cholera Prevention in Ducks.

Fowl cholera is caused by the bacterium Pasteurella multocida, a highly transmissible avian ailment with significant global implications, leading to substantial economic repercussions. The control of fowl cholera outbreaks primarily relies on vaccination using traditional vaccines that are still in use today despite their many limitations. In this research, we describe the development of a genetically engineered herpesvirus of turkeys (HVT) that carries the OmpH gene from P. multocida integrated into UL 45/46 intergenic region using CRISPR/Cas9-NHEJ and Cre-Lox system editing. The integration and expression of the foreign cassettes were confirmed using polymerase chain reaction (PCR), indirect immunofluorescence assays, and Western blot assays. The novel recombinant virus (rHVT-OmpH) demonstrated stable integration of the OmpH gene even after 15 consecutive in vitro passages, along with similar in vitro growth kinetics as the parent HVT virus. The protective efficacy of the rHVT-OmpH vaccine was evaluated in vaccinated ducks by examining the levels of P. multocida OmpH-specific antibodies in serum samples using ELISA. Groups of ducks that received the rHVT-OmpH vaccine or the rOmpH protein with Montanide™ (SEPPIC, Paris, France) adjuvant exhibited high levels of antibodies, in contrast to the negative control groups that received the parental HVT or PBS. The recombinant rHVT-OmpH vaccine also provided complete protection against exposure to virulent P. multocida X-73 seven days post-vaccination. This outcome not only demonstrates that the HVT vector possesses many characteristics of an ideal recombinant viral vaccine vector for protecting non-chicken hosts, such as ducks, but also represents significant research progress in identifying a modern, effective vaccine candidate for combatting ancient infectious diseases.

T- and B-cell Immune Response to COVID Vaccination in Liver Transplant Recipients Based on Interferon-gamma Release Assay and Serum Antibody Levels

Background and Aim: This study aimed to assess T- and B-cell-mediated immune response following administration of two doses of COVID-19 vaccine in liver transplant (LT) recipients. Subjects and Methods: Twenty-eight liver transplant recipients and seven healthy volunteers without prior history of COVID-19 infection were enrolled. All individuals received two doses of COVID-19 vaccine (either Covishield or Covaxin), with the LT recipients receiving them at least 3 months after LT. The results of humoral (COVID-specific IgG) and cell-mediated immune response (interferon [INF]-gamma assay) following vaccination in the LT recipient group were compared with the control group. Results: Both LT recipients and control individuals developed COVID-specific antibodies following vaccination. The LT recipient group showed marginally higher INF-gamma levels with an average of 61.3 pg/ml compared to the control group 42.7 pg/ml (P = 0.051). There was no difference in the immunological response between patients who received the vaccination before or after 6 months posttransplant. There was no difference in response between the two vaccines. Conclusion: LT recipients mounted an immunological response comparable to the control group with both inactivated and viral vector vaccines for COVID-19, when vaccinated with an interval period of 3 months from transplant.

Immunological correlates of protection afforded by PHV02 live, attenuated recombinant vesicular stomatitis virus vector vaccine against Nipah virus disease.

Immune correlates of protection afforded by PHV02, a recombinant vesicular stomatitis (rVSV) vector vaccine against Nipah virus (NiV) disease, were investigated in the African green monkey (AGM) model. Neutralizing antibody to NiV has been proposed as the principal mediator of protection against future NiV infection. Two approaches were used to determine the correlation between neutralizing antibody levels and outcomes following a severe (1,000 median lethal doses) intranasal/intratracheal (IN/IT) challenge with NiV (Bangladesh): (1) reduction in vaccine dose given 28 days before challenge and (2) challenge during the early phase of the antibody response to the vaccine. Reduction in vaccine dose to very low levels led to primary vaccine failure rather than a sub-protective level of antibody. All AGMs vaccinated with the nominal clinical dose (2 × 107 pfu) at 21, 14, or 7 days before challenge survived. AGMs vaccinated at 21 days before challenge had neutralizing antibodies (geometric mean titer, 71.3). AGMs vaccinated at 7 or 14 days before challenge had either undetectable or low neutralizing antibody titers pre-challenge but had a rapid rise in titers after challenge that abrogated the NiV infection. A simple logistic regression model of the combined studies was used, in which the sole explanatory variable was pre-challenge neutralizing antibody titers. For a pre-challenge titer of 1:5, the predicted survival probability is 100%. The majority of animals with pre-challenge neutralizing titer of ≥1:20 were protected against pulmonary infiltrates on thoracic radiograms, and a majority of those with titers ≥1:40 were protected against clinical signs of illness and against a ≥fourfold antibody increase following challenge (indicating sterile immunity). Controls receiving rVSV-Ebola vaccine rapidly succumbed to NiV challenge, eliminating the innate immunity stimulated by the rVSV vector as a contributor to survival in monkeys challenged as early as 7 days after vaccination. It was concluded that PHV02 vaccine elicited a rapid onset of protection and that any detectable level of neutralizing antibody was a functional immune correlate of survival.

Investigation of Reported Anaphylaxis Post COVID-19 Vaccination in Subjects with History of Allergies and Anaphylaxis

Background: Two mRNA COVID-19 vaccines, Pfizer-BioNTech and Moderna, are currently approved in the United States, and one viral-vector vaccine, J&J/Janssen, is authorized for limited use. The Vaccine Adverse Event Reporting System (VAERS) database gathers reports of adverse effects, including anaphylaxis. Objective: In this manuscript, we provide a summary of reported incidence of anaphylaxis rates following administration of the two mRNA and one viral-vector COVID-19 vaccine. Methods: A detailed investigation of the relative risk of anaphylaxis for recipients with or without a prior history of allergy and/or anaphylaxis is also described. Results: Overall reported incidence of anaphylaxis is 4.49 [95% CI: 0.25 – 8.73] cases per million doses administered. Conclusion: The reported risk of anaphylaxis is 1.83 times greater for recipients with prior allergies and no anaphylaxis but 17.70 times greater for recipients with prior allergies and anaphylaxis.

Retinal Vein Occlusion Amongst People Vaccinated by mRNA- and Viral Vector- COVID-19 Vaccines: A Systematic Review.

Vaccines are highly effective in lowering the mortality due to COVID-19. Although several suspected adverse events or side effects after vaccination including retinal vein occlusion (RVO) have been reported. We conducted a systematic review using PRISMA methods to analyze the occurrence of RVO among people vaccinated by COVID-19 mRNA- vs viral vector- vaccines on 4 databases from 1-1-2021 to 31-12-2022 using specified MeSH terms. All included studies were assessed using JBI critical appraisal tools for eligibility. The final included studies are 31 studies (n=78 cases from 75 patients; 3 of these patients suffered twice). The median age of the patients was 61 years (28 to 96 years old) and most of them were female (52.00%). Thirty-nine patients received the mRNA vaccine (52.00%), while 36 patients received the viral vector vaccine (48.00%) before the event. The RVO diagnoses are based on physical examination confirmed by Fluorescein Angiography (FA), and/or Optical Coherence Tomography (OCT). The median time interval between vaccination and RVO was 6 days in the mRNA vaccine group and 4 days in the viral vector vaccine group. Central retinal vein occlusion (CRVO) and Branch Retinal Vein Occlusion (BRVO) were tied as the most common diagnosis in the mRNA vaccine group (20.51% and 20.51%), whilst in the viral vector vaccine group CRVO was the most common diagnosis (17.94%). Most of these cases had good outcomes with improved visual impairment in one or both eyes. From this review, we could not ascertain that the RVO occurs due to the type of COVID-19 vaccines because of the detailed data on the dosage and the history of illness of each patient. However, the awareness that the RVO could develop after COVID-19 vaccination must be taken into consideration, even though it is rare.

Association of seizure with COVID-19 vaccines in persons with epilepsy: A systematic review and meta-analysis.

Seizure aggravation following coronavirus disease 2019 (COVID-19) vaccines is a major cause behind vaccine hesitancy among persons with epilepsy (PwE), resulting in lower immunization rates. We systematically reviewed seizure-activity-related events in PwE following COVID-19 vaccination. We systematically searched PubMed, Web of Science, Scopus, and Cochrane Library, until January 31, 2023, and included articles reporting seizure activity-related events in PwE receiving COVID-19 vaccination. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses were followed. The protocol was registered with PROSPERO (CRD42022312475). Outcomes included pooled incidence proportions of (a) increased seizure frequency, (b) status epilepticus (SE), and (c) change in seizure type. Of the 2207 studies, 16 entered the meta-analysis. The pooled incidence proportion of increased seizure frequency (16 studies-3245 PwE) was 5% (95% CI: 3%-7%, I2 = 52%). Regarding increased seizure frequency, no significant difference was observed between mRNA and viral vector (OR: 1.11, 95% CI: 0.49-2.52, I2 = 0%), and between mRNA and inactivated virus (OR: 1.60, 95% CI: 0.27-9.37; I2 = 0%). The pooled incidence proportion of SE (15 studies-2387 PwE) was 0.08% (95% CI: 0.02%-0.33%, I2 = 0%). Ultimately, the pooled incidence proportion of change in seizure type (7 studies-1172 PwE) was 1% (95% CI: 1%-2%, I2 = 0%). The meta-analysis revealed post-COVID-19-vaccination increased seizure frequency in 5% of PwE, with no difference between mRNA and viral vector or inactivated virus vaccines. Furthermore, we found 0.08% and 1% incidence proportions for postvaccination SE and change in seizure type, respectively. While noteworthy, these values are far less than reports for COVID-19 infection, emphasizing vaccination importance in preventing COVID-19 consequences in PwE.

Timeline kinetics of protective immunity to SARS-CoV-2 upon primary vaccination and humoral response to variants after booster dose

New variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have emerged, imposing the need for periodic booster doses. However, whether booster doses should be applied to the entire population or groups, and the booster doses interval, remains unclear. In this study, we evaluated humoral reactivity kinetics from before the first dose to 180 days after the third booster dose in different schedules in a well-controlled health worker cohort. Among the 2,506 employees, the first 500 vaccinated health workers were invited to participate. The third booster dose was administered 8 months after the first dose. Among the invited participants, 470 were included in the study; 258 received inactivated vaccine CoronaVac (VAC group) and 212 received viral vector vaccine ChAdOx1 (AZV group). The groups were homogeneous in terms of age and sex. 347 participants were followed up after the booster dose with AZV or BNT162b2 (Pfizer, BNT group): 63 with VAC/AZV, 117 with VAC/BNT, 72 with the AZV/AZV and 95 with AZV/BNT schedules. Blood samples were collected immediately before, 28 days after each dose and 180 days after the primary vaccination and booster dose. Anti-SARS-CoV-2 antibodies were measured by chemiluminescence and plaque reduction neutralization test (PRNT). Plasma immune mediators were quantified using a multiplex immunoassay. Geometric mean of antibodies increased 28 days after the second dose with 100 % seroconversion rate in both groups and decreased 180 days after the first dose. In the baseline-seropositive VAC group, the levels of plasma immune mediators increased after the second dose. Booster dose was applied at 4–6 months after the primary vaccination. Heterologous booster in VAC or AZV primary vaccinees were effective maintaining the titers of anti-SARS-CoV-2 antibodies even after 6 months of follow-up. The heterologous schedule induced higher and stable antibody reactivity, even after 180 days, protecting to ancestral (Wuhan), Delta, and Omicron variants.

Management and Characteristics of Embolism and Thrombosis After COVID-19 Vaccination: Scoping Review.

This scoping review aims to 1) identify characteristics of participants who developed embolism and/or thrombotic event(s) after COVID-19 vaccination and 2) review the management during the new vaccine development of the unexpected event(s).This review was conducted following PRISMA for scoping review guidelines. Peer-reviewed articles were searched for studies involving participants with embolism and/or thrombotic event(s) after COVID-19 vaccination with the management described during the early phase after the approval of vaccines. The 12 studies involving 63 participants were included in this review. The majority of participants' ages ranged from 22 to 49 years. The embolism and/or thrombotic event(s) often occur within 30 days post-vaccination. Five of the included studies reported the event after receiving viral vector vaccines and suggested a vaccine-induced immune thrombotic thrombocytopenia as a plausible mechanism. Cerebral venous sinus thrombosis was the most frequently reported post-vaccination thrombosis complication. In summary, the most frequently reported characteristics and management from this review were consistent with international guidelines. Future studies are recommended to further investigate the incidence and additional potential complications to warrant the benefit and safety after receiving COVID-19 vaccine and other newly developed vaccines.

Comparison of heterologous prime-boost immunization strategies with DNA and recombinant vaccinia virus co-expressing GP3 and GP5 of European type porcine reproductive and respiratory syndrome virus in pigs

Vaccination is principally used to control and treat porcine reproductive and respiratory syndrome virus (PRRSV) infection. This study investigated immunogenicity and protective efficacy of heterologous prime-boost regimens in pigs, including recombinant DNA and vaccinia virus vectors coexpressing PRRSV European genotype (EU) isolate GP3 and GP5: group A, pVAX1-EU-GP3-GP5 prime and rddVTT-EU-GP3-GP5 boost; group B, rddVTT-EU-GP3-GP5 prime and pVAX1-EU-GP3-GP5 boost; group C, empty vector pVAX1; group D, E3L gene-deleted vaccinia virus E3L− VTT. Vaccine efficacy was tested in an EU-type PRRSV (Lelystad virus strain) challenge pig model based on evaluating PRRSV-specific antibody responses, neutralizing antibodies, cytokines, T lymphocyte proliferation, CD4+ and CD8+ T lymphocytes, clinical symptoms, viremia and tissue virus loads. Plasmid DNA was delivered as chitosan-DNA nanoparticles, and Quil A (Quillaja) was used to increase vaccine efficiency. All piglets were boosted 21 days post the initial inoculation (dpi) and then challenged 14 days later. At 14, 21, 28 and 35 dpi, groups A and B developed significantly higher PRRSV-specific antibody responses compared with control groups C and D. Two weeks after the boost, significant differences in neutralizing antibody and IFN-γ levels were observed between groups A, C, D and B. At 49 dpi, groups A and B had markedly increased peripheral blood CD3+CD4+ T cell levels. Following virus challenge, group A showed viremia, but organ virus loads were lower than those in other groups. Thus, a heterologous prime-boost vaccine regimen (rddVTT-EU-GP3-GP5 prime, pVAX1-EU-GP3-GP5 boost) can improve humoral- and cell-mediated immune responses to provide resistance to EU-type PRRSV infection in vivo.

Rhesus macaques show increased resistance to repeated SHIV intrarectal exposure following a heterologous regimen of rVSV vector vaccine expressing HIV antigen

ABSTRACT Despite the human immunodeficiency virus (HIV) pandemic continuing worldwide for 40 years, no vaccine to combat the disease has been licenced for use in at risk populations. Here, we describe a novel recombinant vesicular stomatitis virus (rVSV) vector vaccine expressing modified HIV envelope glycoproteins and Ebola virus glycoprotein. Three heterologous immunizations successfully prevented infection by a different clade SHIV in 60% of non-human primates (NHPs). No trend was observed between resistance and antibody interactions. Resistance to infection was associated with high proportions of central memory T-cell CD69 and CD154 marker upregulation, increased IL-2 production, and a reduced IFN-γ response, offering insight into correlates of protection.

Urticaria exacerbations and adverse reactions in patients with chronic urticaria receiving COVID-19 vaccination: Results of the UCARE COVAC-CU study

Concern about disease exacerbations and fear of reactions after coronavirus disease 2019 (COVID-19) vaccinations are common in chronic urticaria (CU) patients and may lead to vaccine hesitancy. We assessed the frequency and risk factors of CU exacerbation and adverse reactions in CU patients after COVID-19 vaccination. COVAC-CU is an international multicenter study of Urticaria Centers of Reference and Excellence (UCAREs) that retrospectively evaluated the effects of COVID-19 vaccination in CU patients aged ≥18 years and vaccinated with ≥1 dose of any COVID-19 vaccine. We evaluated CU exacerbations and severe allergic reactions as well as other adverse events associated with COVID-19 vaccinations and their association with various CU parameters. Across 2769 COVID-19-vaccinated CU patients, most (90%) received at least 2 COVID-19 vaccine doses, and most patients received CU treatment and had well-controlled disease. The rate of COVID-19 vaccination-induced CU exacerbation was 9%. Of 223 patients with CU exacerbation after the first dose, 53.4% experienced recurrence of CU exacerbation after the second dose. CU exacerbation most often started <48 hours after vaccination (59.2%), lasted for a few weeks or less (70%), and was treated mainly with antihistamines (70.3%). Factors that increased the risk for COVID-19 vaccination-induced CU exacerbation included female sex, disease duration shorter than 24 months, having chronic spontaneous versus inducible urticaria, receipt of adenovirus viral vector vaccine, having nonsteroidal anti-inflammatory drug/aspirin intolerance, and having concerns about getting vaccinated; receiving omalizumab treatment and Latino/Hispanic ethnicity lowered the risk. First-dose vaccine-related adverse effects, most commonly local reactions, fever, fatigue, and muscle pain, were reported by 43.5% of CU patients. Seven patients reported severe allergic reactions. COVID-19 vaccination leads to disease exacerbation in only a small number of CU patients and is generally well tolerated.

Superior antibody immunogenicity of a viral-vectored RH5 blood-stage malaria vaccine in Tanzanian infants as compared to adults

RH5 is a leading blood-stage candidate antigen for a Plasmodium falciparum vaccine; however, its safety and immunogenicity in malaria-endemic populations are unknown. A phase 1b, single-center, dose-escalation, age-de-escalation, double-blind, randomized, controlled trial was conducted in Bagamoyo, Tanzania (NCT03435874). Between 12th April and 25th October 2018, 63 healthy adults (18-35 years), young children (1-6 years), and infants (6-11months) received a priming dose of viral-vectored ChAd63 RH5 or rabies control vaccine. Sixty participants were boosted with modified vaccinia virus Ankara (MVA) RH5 or rabies control vaccine 8weeks later and completed 6months of follow-up post priming. Primary outcomes were the number of solicited and unsolicited adverse events post vaccination and the number of serious adverse events over the study period. Secondary outcomes included measures of the anti-RH5 immune response. Vaccinations were well tolerated, with profiles comparable across groups. No serious adverse events were reported. Vaccination induced RH5-specific cellular and humoral responses. Higher anti-RH5 serum immunoglobulin G (IgG) responses were observed post boost in young children and infants compared to adults. Vaccine-induced antibodies showed growth inhibition activity (GIA) invitro against P.falciparum blood-stage parasites; their highest levels were observed in infants. The ChAd63-MVA RH5 vaccine shows acceptable safety and reactogenicity and encouraging immunogenicity in children and infants residing in a malaria-endemic area. The levels of functional GIA observed in RH5-vaccinated infants are the highest reported to date following human vaccination. These data support onward clinical development of RH5-based blood-stage vaccines to protect against clinical malaria in young African infants. Medical Research Council, London, UK.

The most common gastrointestinal alterations in patients with post-COVID syndrome

Post-COVID syndrome may affect the gastrointestinal tract. However, risk factors of post-COVID syndrome are still unknown. We aimed to identify the most common gastrointestinal symptoms, abnormal laboratory findings and risk factors relevant to post-COVID syndrome. In this retrospective study, we included 79 patients admitted to Semmelweis University Department of Surgery, Transplantation and Gastroenterology between October 2020 and September 2022. We investigated clinical data, laboratory findings and determined the major risk factors. Most of the patients were women (46/79), their mean age was 47.6 years and patients were overweight (BMI: 26.3 kg/m2). The most common comorbidities were cardiovascular diseases (21/79), hypertension (20/79), diabetes (11/79) and malignant diseases (9/79). Typical indications for gastroscopy were dyspepsia (16/79) and epigastric pain (10/79). The most common indications for colonoscopy were diarrhea (29/79) and weight loss (28/79). Among abnormal laboratory findings, liver enzymes levels (GOT: 83.5 U/L, GPT: 85 U/L, GGT: 70 U/L) and ferritin (351.5 ng/mL) were higher in post-COVID patients. Typical conditions diagnosed by gastroscopy, colonoscopy and abdominal ultrasound were gastroesophageal reflux disease (11/26), irritable bowel syndrome (2/19) and diffuse hepatic lesions, respectively. The number of unvaccinated patients was higher compared to those receiving any COVID-19 vaccines (58% vs. 29%). Of the vaccinated patients, 12 patients received mRNA vaccines (10 Pfizer-BioNTech, 2 Moderna) and 6 patients received viral vector vaccines (2 AstraZeneca, 4 Sputnik V). We identified female gender, obesity, cardiovascular diseases, cancer, hypertension and diabetes as major risk factors of post-COVID syndrome. Vaccinated status may prevent post-COVID gastrointestinal symptoms. Orv Hetil. 2023; 164(31): 1206-1212.

Tracing down the Updates on Dengue Virus-Molecular Biology, Antivirals, and Vaccine Strategies.

Nearly half of the world is at risk of developing dengue infection. Dengue virus is the causative agent behind this public healthcare concern. Millions of dengue cases are reported every year, leading to thousands of deaths. The scientific community is working to develop effective therapeutic strategies in the form of vaccines and antiviral drugs against dengue. In this review, a methodological approach has been used to gather data from the past five years to include the latest developments against the dengue virus. Different therapeutics and antiviral targets against the dengue virus are at different stages of development, but none have been approved by the FDA. Moreover, various vaccination strategies have also been discussed, including attenuated virus vaccines, recombinant subunit vaccines, viral vector vaccines, DNA vaccines, nanotechnology, and plant-based vaccines, which are used to develop effective vaccines for the dengue virus. Many dengue vaccines pass the initial phases of evaluation, but only two vaccines have been approved for public use. DENGVAXIA is the only FDA-approved vaccine against all four stereotypes of the dengue virus, but it is licensed for use only in individuals 6-16 years of age with laboratory-confirmed previous dengue infection and living in endemic countries. Takeda is the second vaccine approved for use in the European Union, the United Kingdom, Brazil, Argentina, Indonesia, and Thailand. It produced sustained antibody responses against all four serotypes of dengue virus, regardless of previous exposure and dosing schedule. Other dengue vaccine candidates at different stages of development are TV-003/005, TDENV PIV, V180, and some DNA vaccines. There is a need to put more effort into developing effective vaccines and therapeutics for dengue, as already approved vaccines and therapeutics have limitations. DENGVAXIA is approved for use in children and teenagers who are 6-16 years of age and have confirmed dengue infection, while Takeda is approved for use in certain countries, and it has withdrawn its application for FDA approval.

Post-genomic era in agriculture and veterinary science: successful and proposed application of genetic targeting technologies.

Gene editing tools have become an indispensable part of research into the fundamental aspects of cell biology. With a vast body of literature having been generated based on next generation sequencing technologies, keeping track of this ever-growing body of information remains challenging. This necessitates the translation of genomic data into tangible applications. In order to address this objective, the generated Next Generation Sequencing (NGS) data forms the basis for targeted genome editing strategies, employing known enzymes of various cellular machinery, in generating organisms with specifically selected phenotypes. This review focuses primarily on CRISPR/Cas9 technology in the context of its advantages over Zinc finger proteins (ZNF) and Transcription activator-like effector nucleases (TALEN) and meganucleases mutagenesis strategies, for use in agricultural and veterinary applications. This review will describe the application of CRISPR/Cas9 in creating modified organisms with custom-made properties, without the undesired non-targeted effects associated with virus vector vaccines and bioactive molecules produced in bacterial systems. Examples of the successful and unsuccessful applications of this technology to plants, animals and microorganisms are provided, as well as an in-depth look into possible future trends and applications in vaccine development, disease resistance and enhanced phenotypic traits will be discussed.

Vaccination is the most effective and best way to avoid the disease of COVID-19.

Most of the vaccines that are effective against SARS-CoV-2 have used the following functional strategies: inactivated viruses, live attenuated viruses, viral vector-based vaccines, subunit vaccines, recombinant proteins, and DNA/RNA vaccines. Among the vaccines that stimulate the host's immune system with the help of DNA are: undergoing Phase 2/3 trials including INO-4800 (International Vaccine Institute; Inovio Pharmaceuticals), Symvivo, Canada-COVID19 (AnGes, Inc.); GX-19 (Genexine, Inc.). BNT162b2and mRNA-1273 vaccines were made by BioNTech/Pfizer/Fosun Pharma group and Moderna/NIAID group, respectively, which are considered as types of RNA vaccines. Vaccines that are based on the viral vector are AstraZeneca, Sputonium, and Johnson-Jensen. Among the inactive viral vaccines, the following can be mentioned: CoronaVac (Sinovac) WIBP vaccine (Wuhan Institute of Biological Products, Sinopharm), BBIBPCorV (Beijing Institute of Biological Products, Sinopharm), BBV152/Covaxin (Bharat Biotech, ICMR, National Institute of Virology) And among the protein-based/subunit vaccines, the following can be counted: NVX-CoV2373: (Novavax); SCB-2019 vaccine (Clover Biopharmaceuticals AUS Pty Ltd.); Covax-19 (GeneCure Biotechnologies; Vaxine Pty Ltd.) mRNA vaccines, viral vector vaccines, and protein subunit vaccines cannot cause disease because these vaccines stimulate the immune system to produce antibodies against virus proteins instead of the virus itself (or its antigen). MRNA vaccines increase SARS-CoV-2 proteins and ultimately stimulate the production of T and B lymphocytes. The epidemic of HCoVs and their destructive and harmful effects on life has caused the scientific community to seek the production of an effective and efficient vaccine before its catastrophic release. We all need to know that none of us will be healed until the other is healed. The purpose of this review article is to present a selection of existing knowledge in the field of fighting and preventing the coronavirus.

Next-Generation TB Vaccines: Progress, Challenges, and Prospects.

Tuberculosis (TB), caused by Mycobacterium tuberculosis (MTB), is a prevalent global infectious disease and a leading cause of mortality worldwide. Currently, the only available vaccine for TB prevention is Bacillus Calmette-Guérin (BCG). However, BCG demonstrates limited efficacy, particularly in adults. Efforts to develop effective TB vaccines have been ongoing for nearly a century. In this review, we have examined the current obstacles in TB vaccine research and emphasized the significance of understanding the interaction mechanism between MTB and hosts in order to provide new avenues for research and establish a solid foundation for the development of novel vaccines. We have also assessed various TB vaccine candidates, including inactivated vaccines, attenuated live vaccines, subunit vaccines, viral vector vaccines, DNA vaccines, and the emerging mRNA vaccines as well as virus-like particle (VLP)-based vaccines, which are currently in preclinical stages or clinical trials. Furthermore, we have discussed the challenges and opportunities associated with developing different types of TB vaccines and outlined future directions for TB vaccine research, aiming to expedite the development of effective vaccines. This comprehensive review offers a summary of the progress made in the field of novel TB vaccines.

Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection

BackgroundThere is limited data directly comparing the effectiveness of different COVID-19 vaccines. MethodsWe compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14–63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics. ResultsAs a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82–1.30), 1.19 (0.95–1.49), 1.70 (1.46–1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00–1.04), 1.20 (1.10–1.32), 1.39 (1.20–1.60). ConclusionsOur findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.

NVX-CoV2373-induced T- and B-cellular immunity in immunosuppressed people with multiple sclerosis that failed to respond to mRNA and viral vector SARS-CoV-2 vaccines.

Immunological response to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccination is important, especially in people with multiple sclerosis (pwMS) on immunosuppressive therapies. This study aims to determine whether adjuvanted protein-based vaccine NVX-CoV2373 is able to induce an immune response to SARS-CoV-2 in pwMS with inadequate responses to prior triple mRNA/viral vector vaccination. We conducted a single-center, prospective longitudinal cohort study at the MS Center in Dresden, Germany. In total, 65 participants were included in the study in accordance with the following eligibility criteria: age > 18 years, immunomodulatory treatment, and insufficient T-cellular and humoral response to prior vaccination with at least two doses of SARS-CoV-2 mRNA (BNT162b2, mRNA-1273) or viral vector vaccines (AZD1222, Ad26.COV2.S). Intramuscular vaccination with two doses of NVX-CoV2373 at baseline and 3 weeks of follow-up. The development of SARS-CoV-2-specific antibodies and T-cell responses was evaluated. For the final analysis, data from 47 patients on stable treatment with sphingosine-1-phosphate receptor (S1PR) modulators and 17 on ocrelizumab were available. The tolerability of the NVX-CoV2373 vaccination was overall good and comparable to the one reported for the general population. After the second NVX-CoV2373 vaccination, 59% of S1PR-modulated patients developed antispike IgG antibodies above the predefined cutoff of 200 binding antibody units (BAU)/ml (mean, 1,204.37 [95% CI, 693.15, 2,092.65] BAU/ml), whereas no clinically significant T-cell response was found. In the subgroup of the patients on ocrelizumab treatment, 23.5% developed antispike IgG > 200 BAU/ml (mean, 116.3 [95% CI, 47.04, 287.51] BAU/ml) and 53% showed positive spike-specific T-cellular responses (IFN-gamma release to antigen 1: mean, 0.2 [95% CI, 0.11, 0.31] IU/ml; antigen 2: mean, 0.24 [95% CI, 0.14, 0.37]) after the second vaccination. Vaccination with two doses of NVX-CoV2373 was able to elicit a SARS-CoV-2-specific immune response in pwMS lacking adequate immune responses to previous mRNA/viral vector vaccination. For patients receiving S1PR modulators, an increase in anti-SARS-CoV-2 IgG antibodies was detected after NVX-CoV2373 vaccination, whereas in ocrelizumab-treated patients, the increase of antiviral T-cell responses was more pronounced. Our data may impact clinical decision-making by influencing the preference for NVX-CoV2373 vaccination in pwMS receiving treatment with S1PR modulation or anti-CD20 treatment.

COVID-19 inactivated and non-replicating viral vector vaccines induce regulatory training phenotype in human monocytes under epigenetic control.

Trained immunity is the enhanced innate immune response resulting from exposure to pathogens or vaccines against an unrelated pathogen stimulus. Certain vaccines induce a memory like response in monocytes and NK cells, leading to modulation in cytokine production, metabolic changes, and modifications in histone patterns. Here, we hypothesized that vaccination against SARS-CoV-2 could induce the training of monocytes in addition to stimulating the adaptive immune response. Therefore, we aimed to investigate the immunophenotyping, cytokine and metabolic profile of monocytes from individuals who were completely immunized with two doses of inactivated COVID-19 vaccine or non-replicating viral vector vaccine. Subsequently, we investigated the epigenetic mechanisms underlying monocyte immune training. As a model of inflammatorychallenge, to understand if the monocytes were trained by vaccination and how they were trained, cells were stimulated in vitro with the endotoxin LPS, an unrelated stimulus that would provoke the effects of training. When challenged in vitro, monocytes from vaccinated individuals produced less TNF-α and those who received inactivated vaccine produced less IL-6, whereas vaccination with non-replicating viral vector vaccine induced more IL-10. Inactivated vaccine increased classical monocyte frequency, and both groups showed higher CD163 expression, a hallmark of trained immunity. We observed increased expression of genes involved in glycolysis and reduced IRG1 expression in vaccinated subjects, a gene associated with the tolerance phenotype in monocytes. We observed that both vaccines reduced the chromatin accessibility of genes associated with the inflammatory response, the inactivated COVID-19 vaccine trained monocytes to a regulatory phenotype mediated by histone modifications in the IL6 and IL10 genes, while the non-replicating viral vector COVID-19 vaccine trained monocytes to a regulatory phenotype, mediated by histone modifications in the IL6, IL10, TNF, and CCL2 genes. Our findings support the recognized importance of adopting vaccination against SARS CoV-2, which has been shown to be effective in enhancing the adaptive immune response against the virus and reducing mortality and morbidity rates. Here, we provide evidence that vaccination also modulates the innate immune response by controlling the detrimental inflammatory response to unrelated pathogen stimulation.