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.

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.

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.

The Mycobacterium tuberculosis PhoPR virulence system regulates expression of the universal second messenger c-di-AMP and impacts vaccine safety and efficacy.

Cyclic (di)nucleotides act as universal second messengers endogenously produced by several pathogens. Specifically, the roles of c-di-AMP in Mycobacterium tuberculosis immunity and virulence have been largely explored, although its contribution to the safety and efficacy of live tuberculosis vaccines is less understood. In this study, we demonstrate that the synthesis of c-di-AMP is negatively regulated by the M. tuberculosis PhoPR virulence system. Accordingly, the live attenuated tuberculosis vaccine candidate M. tuberculosis vaccine (MTBVAC), based on double phoP and fadD26 deletions, produces more than 25- and 45-fold c-di-AMP levels relative to wild-type M. tuberculosis or the current vaccine bacille Calmette-Guérin (BCG), respectively. Secretion of this second messenger was exclusively detected in MTBVAC but not in M. tuberculosis or in BCG. We also demonstrate that c-di-AMP synthesis during in vitro cultivation of M. tuberculosis is a growth-phase- and medium-dependent phenotype. To uncover the role of this metabolite in the vaccine properties of MTBVAC, we constructed and validated knockout and overproducing/oversecreting derivatives by inactivating the disA or cnpB gene, respectively. All MTBVAC derivatives elicited superior interleukin-1ß (IL-1ß) responses compared with BCG during an in vitro infection of human macrophages. However, both vaccines failed to elicit interferon ß (IFNß) activation in this cellular model. We found that increasing c-di-AMP levels remarkably correlated with a safer profile of tuberculosis vaccines in the immunodeficient mouse model. Finally, we demonstrate that overproduction of c-di-AMP due to cnpB inactivation resulted in lower protection of MTBVAC, while the absence of c-di-AMP in the MTBVAC disA derivative maintains the protective efficacy of this vaccine in mice.

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.

Old vaccines for new infections: Exploiting innate immunity to control COVID-19 and prevent future pandemics.

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