Prospects of lassa fever candidate vaccines

Background: Lassa fever is an acute viral haemorrhagic disease caused by the Lassa virus (LASV). It is endemic in West Africa and infects about 300,000 people each year, leading to approximately 5000 deaths annually. The development of the LASV vaccine has been listed as a priority by the World Health Organization since 2018. Considering the accelerated development and availability of vaccines against COVID-19, we set out to assess the prospects of LASV vaccines and the progress made so far. Materials and Methods: We reviewed the progress made on twenty-six vaccine candidates listed by Salami et al. (2019) and searched for new vaccine candidates through Google Scholar, PubMed, and DOAJ from June to July 2021. We searched the articles published in English using keywords that included "vaccine" AND "Lassa fever" OR "Lassa virus" in the title/. Results: Thirty-four candidate vaccines were identified - 26 already listed in the review by Salami et al. and an additional 8, which were developed over the last seven years. 30 vaccines are still in the pre-clinical stage while 4 of them are currently undergoing clinical trials. The most promising candidates in 2019 were vesicular stomatitis virus-vectored vaccine and live-attenuated MV/LASV vaccine;both had progressed to clinical trials. Conclusions: Despite the focus on COVID-19 vaccines since 2020, LASV vaccine is under development and continues to make impressive progress, hence more emphasis should be put into exploring further clinical studies related to the most promising types of vaccines identified.

Prospect of Vaccinia virus vector vaccine for wildlife

Against a pandemic of emerged infectious disease, COVID-19, new generation vaccines based on nucleic acids or recombinant viruses, which had not been used as vaccines in humans, have been inoculated and shown to be successful. They are, however, heat-labile and need a cold-chain including deep-freezers for storage and transportation. Vaccinia virus (VAC) vector vaccine (VACV) is a pioneer of new generation of vaccines constructed by using molecular biological technology. VACV, which has contributed to eradication of smallpox, has excellent characteristics of vaccinia virus such as a high heat-stability and long-lasting immunological effects. It is possible to distinguish the immunological responses of vaccination from those of natural infections. We started our developmental researches 35 years ago, using attenuated VAC strains established in Japan. In this article, we first describe the early researches of VACVs;development of two VACVs for Bovine leukemia virus and Rinderpest morbillivirus antigens and their protective immunity in large mammals, sheep and cows. Second, application of VACV is described;Rabies-VACV, which has already been licensed, used in the field in Europe and USA, and resulted in a prominent decrease of rabies. Then, current status of VACV research is described;non-replicating VACVs in mammalian cells have been developed as new-generation and ultimately-safe vaccines. We discuss the possibility of future application of VACV for wildlife.

Vaccination in children with immune-mediated disorders.

OBJECTIVE: To present an updated review of recommendations for the vaccination of children with immune-mediated diseases, with an emphasis on rheumatic and inflammatory diseases. SOURCE OF DATA: Studies published in the PubMed and Scielo databases between 2002 and 2022, Guidelines of Brazilian Scientific Societies, Manuals and Technical Notes of the Ministry of Health of Brazil, on current immunization schedules for special populations. DATA SYNTHESIS: Immunosuppressive drugs and biological agents reduce the immunogenicity of vaccines and favor susceptibility to infections. The safety and efficacy of immunogens are important points for vaccination in children with immune-mediated diseases. The safety threshold of a vaccine applied to immunocompromised individuals can be reduced when compared to healthy individuals. Very often, the recommendations for the immunization of children with immune-mediated diseases follow the recommendations for immunocompromised patients. Vaccination against COVID-19, on the other hand, should ideally occur when the disease is stabilized and in the absence of a low degree of immunosuppression. The patients should be informed about the possibility that the immunization may fail during treatment with immunosuppressants. Specific vaccination schedules should be considered to ensure better protection. CONCLUSIONS: Recent studies have allowed updating the recommendations on the safety and immunogenicity of vaccination in children with immune-mediated diseases, especially for live attenuated vaccines. There is a scarcity of data on the safety and efficacy of COVID-19 vaccines in patients, particularly pediatric patients, with rheumatic diseases. The completion of ongoing studies is expected to help guide recommendations on COVID-19 vaccines in this group of patients.

Propagation of SARS-CoV-2 in a Closed Cell Culture Device: Potential GMP Compatible Production Platform for Live-Attenuated Vaccine Candidates under BSL-3 Conditions?

Live-attenuated SARS-CoV-2 vaccines present themselves as a promising approach for the induction of broad mucosal immunity. However, for initial safety assessment in clinical trials, virus production requires conditions meeting Good Manufacturing Practice (GMP) standards while maintaining biosafety level 3 (BSL-3) requirements. Since facilities providing the necessary complex ventilation systems to meet both requirements are rare, we here describe a possibility to reproducibly propagate SARS-CoV-2 in the automated, closed cell culture device CliniMACS Prodigy® in a common BSL-3 laboratory. In this proof-of-concept study, we observed an approximately 300-fold amplification of SARS-CoV-2 under serum-free conditions with high lot-to-lot consistency in the infectious titers obtained. With the possibility to increase production capacity to up to 3000 doses per run, this study outlines a potential fast-track approach for the production of live-attenuated vaccine candidates based on highly pathogenic viruses under GMP-like conditions that may contribute to pandemic preparedness.

Safety of the live at attenuated vaccine avishield IB GI-13 against infectious bronchitis in SPF chickens during laying period

Avian infectious bronchitis (IB) is an economically important, highly contagious, acute disease of Chickens caused by a single-stranded positive RNA Virus that belongs to the Coronaviridae family. The Virus can replicate in the oviduct and cause permanent damage in young hens resulting in the false layer occurrence. In laying hens, infectious bronchitis Virus (IBV) infections can cause a severe decline in egg production and a number of effects on egg quality and reduced hatchability. The most effective means of controlling IB in poultry is vaccination. In the areas with increased pressure of circulating field challenge Virus, live attenuated vaccines are also used during the laying period with the intention of keeping local protection of the respiratory tract at a high level. The vaccine strain IB V-173/11 contained in Avishield IB GI-13 vaccine is a strain that genetically (S1 gene) belongs to GI-13 lineage and antigenically to 793B IBV serotype. Viral infections of this serotype occur frequently in Europe and therefore most vaccination programs in broilers, layers and breeders along a live IBV vaccine of the Massachusetts serotype also include a live vaccine of the 793B serotype, GI-I3 lineage. In this paper, results of a safety evaluation of live attenuated IB vaccine strain V-173/11, when administered by spray method in a ten-fold maximum dose repeated by one maximum dose in 28-week-old specific pathogen free (SPF) layer Chickens are presented. As a control, non-vaccinated SPF layer chickens were included in the study. The vaccine is considered to be safe when used in laying period because no vaccinated chicken showed abnormal local or systemic reactions or signs of IB related disease, no chicken died from the causes attributable to the vaccine, egg quality was not altered, and there was no statistically significant difference in. egg production between the vaccinated and non-vaccinated group.

Intranasal administration of cold-adapted live-attenuated SARS-CoV-2 candidate vaccine confers protection against SARS-CoV-2.

With the COVID-19 pandemic globally, the ongoing threat of new challenges of mucosal infections was once again reminded human beings. Hence, access to the next-generation vaccine to elicit mucosal immunity is required to reduce virus shedding. SARS-CoV-2 retains a unique polybasic cleavage motif in its spike protein, recognized by the host furin protease. The proteolytic furin cleavage site at the junction of S1/S2 glycoprotein plays a key role in the pathogenesis of SARS-CoV-2. Here, we examined the protective immunity of a double-deleted PRRA/GTNGTKR motifs cold-adapted live-attenuated candidate vaccines as a called "KaraVac." using a hamster animal model of infected attenuated SARS-CoV-2. The KaraVac vaccinated hamsters were challenged against the wild-type (WT) SARS-CoV-2. No apparent bodyweight loss and histopathological lesions were observed in the hamsters. The establishment of sterilizing immunity was induced via stimulating a robust neutralizing antibody (NAb) response in a hamster model. Consequently, deletions in the spike sequence and inoculation into hamsters provide resistance to the subsequent challenge with WT SARS-CoV-2. We have suggested that deletion of the furin cleavage site and GTNGTKR motifs in the spike sequence attenuates the virus from the parental strain and can be used as a potent immunogen.

Prevention and Control of Porcine Epidemic Diarrhea: The Development of Recombination-Resistant Live Attenuated Vaccines.

Porcine epidemic diarrhea (PED), causing up to 100% mortality in neonatal pigs, is a highly contagious enteric disease caused by PED virus (PEDV). The highly virulent genogroup 2 (G2) PEDV emerged in 2010 and has caused huge economic losses to the pork industry globally. It was first reported in the US in 2013, caused country-wide outbreaks, and posed tremendous hardship for many pork producers in 2013-2014. Vaccination of pregnant sows/gilts with live attenuated vaccines (LAVs) is the most effective strategy to induce lactogenic immunity in the sows/gilts and provide a passive protection via the colostrum and milk to suckling piglets against PED. However, there are still no safe and effective vaccines available after about one decade of endeavor. One of the biggest concerns is the potential reversion to virulence of an LAV in the field. In this review, we summarize the status and the major obstacles in PEDV LAV development. We also discuss the function of the transcriptional regulatory sequences in PEDV transcription, contributing to recombination, and possible strategies to prevent the reversion of LAVs. This article provides insights into the rational design of a promising LAV without safety issues.

Vaccinations in pregnancy.

Vaccinations are a cost-effective means of preventing disease. They may be recommended primarily for maternal benefit or for prevention of intrauterine fetal or early neonatal infection. Data from the International Network of Obstetric Survey Systems relating to the COVID-19 pandemic showed that for all countries studied (the UK, the Netherlands, Norway, Denmark, Finland and Italy), at least 80% of pregnant women admitted to critical care were unvaccinated. In the UK this figure was 98%. The MBRRACE-UK 2014 report, covering 2009-2012 during the H1N1 epidemic, demonstrated that one in eleven maternal mortalities were directly from influenza virus: more than half could have been prevented by the flu vaccine in pregnancy. Research is ongoing to develop additional vaccines for infections that cause detrimental effects to pregnant women and their infants. Theoretical concerns regarding adverse effects to the fetus and lack of efficacy have, in general, not been confirmed by clinical evidence. Nevertheless, live attenuated vaccines remain contraindicated due to risk of fetal infection. As with any clinical decision, advice on antenatal vaccination should be based on the balance of risks and benefits to mother and fetus. This article aims to guide such decisions by discussing the issues surrounding commonly used vaccines and presenting current UK guidelines.

Overview of COVID-19 vaccine development strategy

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was identified as the cause of coronavirus disease 20019 (COVID19) pandemic which first emerged in December 2019 in Wuhan city, China. Currently, a vaccine is urgently needed to control the COVID-19 pandemic. Several vaccine candidates are under development and some are in the final stage of clinical trials. The COVID-19 vaccination aims to reduce morbidity and mortality rates, achieve herd immunity to prevent and protect the society, strengthen the health system, maintain productivity and minimize social and economic impacts. Before approval, vaccines have to undergo several clinical trials to ensure its safety profile, efficacy, duration of immune system resistance, and adverse effect. Various strategies have been used in the development of vaccines including viral vector vaccines, nucleic acid vaccines, inactivated virus, live attenuated virus, subunit protein, and virus-like particle vaccine. Each strategy has its own advantages and disadvantages.

COVID-19 vaccine and hematopoietic stem cell transplantation

In the pandemic era of coronavirus disease 2019 (COVID-19), vaccines have been developed and approved to control the pandemic that might reduce the COVID-19 mortality. Transplant recipients are among the high-risk groups and are more susceptible to COVID-19 infection. According to the available data about COVID-19 vaccines, some platform technologies include vector-based, inactivated, protein subunit, virus-like particles, mRNA, and DNA vaccines (1). There are several guidelines about vaccination in immunocompromised individuals for both non-live- and live vaccines. However, there are still limited evidence-based data about COVID-19 vaccines in the hematopoietic stem cell transplantation (HSCT), and establishing a proper recommendation for vaccination in these patients would be challenging (2, 3). Transplant recipients may have shown lesser responses to the vaccines compared with the general population, and it is unknown to what extent the vaccine is effective in this group of patients. Also, in many countries, the vaccination schedule is not adjustable by the patients or physicians, and selecting a particular time window for the best efficacy of immunization is impossible. In this regard, the main concern in the patients treated with immunosuppressive drugs is not worsening symptoms and disease following vaccination. The most critical issue is determining the best time for vaccination to increase its efficacy. Here are some considerations about vector-based, inactivated, and mRNA- nanoparticle vaccines, but most evidence is not based on the results of cohort or clinical trial studies. Before HSCT, patients could receive the COVID-19 vaccine if they are not already immunosuppressed. According to evidence about other inactivated vaccines, such as the influenza vaccine, the interval to start the conditioning regimen could be considered 2 - 4 weeks following the vaccination (4). In autologous HSCT patients, COVID-19 vaccination can be considered 1 - 3 months after transplantation if there has been a community outbreak. If acquiring or transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was well controlled, vaccination could be withheld after six months of transplantation. In the current pandemic, COVID-19 vaccination in allogeneic HSCT patients could be considered at least three months after transplantation. If transmission of SARS-CoV-2 was controlled, vaccination could be withheld after six months of transplantation (4-6). Vaccination of patients with chronic graft versus host disease (cGVHD) receiving less than 20 mg/day prednisolone (or equivalent) for less than 2 weeks, can be considered similar to the HSCT recipients with no GVHD (5). Vaccines in HSCT recipients with active SARS-CoV-2 infection are not effective thus, receiving the vaccine is not recommended. If an HSCT recipient has received the COVID-19 vaccine before HSCT, re-vaccination after transplantation is suggested (6). The administration of the vaccine is considered when the immune system acquired functional competence. Transplant donation should not be delayed due to the vaccination of the donor to protect the patients in case the transplant is urgent (6). It was reported that recipients who have received anti-B cell antibodies might get the vaccine at 3 - 6 months after the administration and four weeks before the next course of B cell-depleting therapy. If this time window was not possible, vaccination can be regarded under B-cell depleting therapy, considering a suboptimal response to the vaccine (7). It should be noted that the effects of rituximab may last for six months or even a year. Also, the decision to order vaccines following the use of rituximab should be based on the level of immunoglobulins and CD19. There is no strong evidence for the short duration of vaccination following the use of rituximab (such as 3 to 6 months). However, despite the low efficacy of the vaccine in such conditions, it is recommended to get the vaccine whenever available. It is reasonable that recipients who have received therapy with antithy

Molecular biology and genetic studies in combating the new coronavirus (COVID-19) outbreak

The new type of coronavirus (SARS-CoV-2), which is transmitted from person to person and causes Severe Acute Respiratory Distress Syndrome (SARS), emerged in Wuhan, China in December 2019. The definitive diagnosis of the coronavirus, which is transmitted from person to person through droplets, is given through PCR-based tests. The continuation of the COVID-19 pandemic has made it necessary to develop an effective vaccine against SARS-CoV-2. Vaccines developed against COVID-19 can be classified as inactivated/live virus vaccines, recombinant protein vaccines/vectored vaccines or RNA/DNA vaccines. This review aims to give information about the molecular structure and genetic features of SARSCoV- 2 virus, laboratory diagnostic methods, potential therapeutic drugs and vaccine studies.

Adult Bacille Calmette-Gu..rin vaccination during the pandemic of COVID-19 in India

The pandemic of coronavirus disease 2019 (COVID-19) has impacted many health service systems including tuberculosis (TB) control in India. As of October 19, 2020, India has the second highest number of COVID cases globally, amounting to 7.55 million reported COVID-19 cases and 114,640 deaths. Indian Council of Medical Research's Bacille Calmette-Gu..rin vaccine study among elderly individuals in COVID-19 hotspots involves the following strategy such as COVID screening by antibody testing and real-time reverse-transcriptase-polymerized chain reaction, TB screening by symptom and chest X-ray, and those who are tested positive will be linked to the national tuberculosis elimination programme for the management, this could be a sustainable new strategy in combating the two pandemic diseases, especially in India with high TB and COVID-19 disease burden. To ensure no one is left behind, the paradigm shift of screening for TB and COVID should be in place to sustain the progress made toward TB elimination.

Enhanced High Mutation Rate and Natural Selection to Produce Attenuated Viral Vaccine with CRISPR Toolkit in RNA Viruses especially SARS-CoV-2.

The best and most effective way to combat pandemics is to use effective vaccines and live attenuated vaccines are among the most effective vaccines. However, one of the major problems is the length of time it takes to get the attenuated vaccines. Today, the CRISPR toolkit (Clustered Regularly Inerspaced Short Palindromic Repeats) has made it possible to make changes with high efficiency and speed. Using this toolkit to make point mutations on the RNA virus's genome in a coculture of permissive and nonpermissive cells and under controlled conditions can accelerate changes in the genome and accelerate natural selection to obtain live attenuated vaccines.

Effectiveness of Booster Measles-Mumps-Rubella Vaccination in Lower COVID-19 Infection Rates: A Retrospective Cohort Study in Turkish Adults.

OBJECTIVE: The aim of this study was to investigate the effectiveness of booster vaccination of adults with measles-mumps-rubella in the COVID-19 infection rates. METHODS: In order to investigate this hypothesis, we tested COVID-19 positivity rate through PCR assay on the participants (n=245; male), who had to share the same student accommodation together with the same dining hall to provide governmental service. Participants were divided into two groups based on their booster vaccination status with measles-mumps-rubella: the non-vaccinated group (n=207) and the vaccinated group (n=38). The rate of COVID-19 seropositivity, age, body mass index (BMI), active smoking and presence of comorbidity were also measured and recorded. RESULTS: All of the participants were healthy, and age distribution, comorbidity rates, active smoking status and BMI did not vary significantly among the two groups (p=0.305, p=0.594, p=0.280, and p=0.922, respectively). About 36.7% (n=90) of the participants were found to be COVID-19 positive by PCR among which the non-vaccinated cases had higher rates of COVID-19 seropositivity than the vaccinated cases (40.6% vs 15.8%) (OR=3.6, 95%CI: 1.5-9.0, p=0.004). CONCLUSION: Based on these results, we cautiously predict that immunity produced by MMR vaccination boosters may provide some degree of protection against COVID-19 in the adult population.

Could "trained immunity" be induced by live attenuated vaccines protect against COVID-19? Review of available evidence.

Coronavirus disease 2019 (COVID-19) represents a severe global public health threat. Caused by SARS-Cov-2, COVID-19 is characterized by high transmission rate that correlates with high viral load. The full clinical spectrum of the illness, the prevalence rates of mild symptomatic and asymptomatic cases, and the case fatality rates are still poorly understood, highlighting the importance of early preventive measures. Unfortunately, appropriate vaccination against SARS-Cov-2 is not yet available. Unless a target vaccine is developed, COVID-19 impacts will be devastating. "Trained immunity" (TI), which could be induced by live attenuated vaccines (LAVs), is a potential public health preventive approach to boost the host immune system. Trained innate immune cells demonstrated phenotypical and functional changes leading them to acquire immunological memory and amplify their responses against subsequent infections. This phenomenon could have important public health preventive implications by harnessing the early immune responses against COVID-19, restricting its progression, and suppressing its infectivity. Some LAVs have induced a broad, nonspecific, protection against unrelated pathogens and decreased mortality from conditions other than the targeted infectious diseases. This review summarizes the relevant literature and 1) emphasizes the role of available LAVs as potential stimulants for TI and 2) proposes this phenomenon as a potential preventive approach against COVID-19 that needs thoughtful consideration and further investigation. Clinical trials in this field are then urgently needed in line of vaccine and treatment unavailability. This is specifically true when considering two evolving scenarios; the virus spread may not diminish with warm weather, and that it will erupt a second-hit severe outbreak next winter.

New Points of Departure for More Global Influenza Vaccine Use.

Each year, influenza causes a significant acute respiratory disease burden. In addition, influenza pandemics periodically occur. Annual vaccination is the best tool for influenza prevention, but its effectiveness can vary from year to year. The narrow specificity of conventional vaccines and the drug resistance of currently circulating viruses reduce the effectiveness of prophylaxis and treatment and require the development of new broad-spectrum preparations. Furthermore, the challenge of creating a highly effective universal influenza vaccine takes on renewed intensity in the face of the COVID-19 pandemic.

Could an Unrelated Live Attenuated Vaccine Serve as a Preventive Measure To Dampen Septic Inflammation Associated with COVID-19 Infection?

We propose the concept that administration of an unrelated live attenuated vaccine, such as MMR (measles, mumps, rubella), could serve as a preventive measure against the worst sequelae of coronavirus disease 2019 (COVID-19). There is mounting evidence that live attenuated vaccines provide nonspecific protection against lethal infections unrelated to the target pathogen of the vaccine by inducing "trained" nonspecific innate immune cells for improved host responses against subsequent infections. Mortality in COVID-19 cases is strongly associated with progressive lung inflammation and eventual sepsis. Vaccination with MMR in immunocompetent individuals has no contraindications and may be especially effective for health care workers who can easily be exposed to COVID-19. Following the lead of other countries conducting clinical trials with the live attenuated Mycobacterium bovis BCG (BCG) vaccine under a similar concept, a clinical trial with MMR in high-risk populations may provide a "low-risk-high-reward" preventive measure in saving lives during this unprecedented COVID-19 pandemic.