Biodegradable Polyester Nanoparticle Vaccines Deliver Self-Amplifying mRNA in Mice at Low Doses

Delivery of self-amplifying mRNA (SAM) has high potential for infectious disease vaccination due to its self-adjuvanting and dose-sparing properties. Yet a challenge is the susceptibility of SAM to degradation and the need for SAM to reach the cytosol fully intact to enable self-amplification. Lipid nanoparticles are successfully deployed at incredible speed for mRNA vaccination, but aspects such as cold storage, manufacturing, efficiency of delivery, and the therapeutic window can benefit from further improvement. To investigate alternatives to lipid nanoparticles, a class of >200 biodegradable end-capped lipophilic poly(beta-amino ester)s (PBAEs) that enable efficient delivery of SAM in vitro and in vivo as assessed by measuring expression of SAM encoding reporter proteins is developed. The ability of these polymers to deliver SAM intramuscularly in mice is evaluated, and a polymer-based formulation that yields up to 37-fold higher intramuscular (IM) expression of SAM compared to injected naked SAM is identified. Using the same nanoparticle formulation to deliver a SAM encoding rabies virus glycoprotein, the vaccine elicits superior immunogenicity compared to naked SAM delivery, leading to seroconversion in mice at low RNA injection doses. These biodegradable nanomaterials may be useful in the development of next-generation RNA vaccines for infectious diseases.Copyright © 2023 The Authors. Advanced Therapeutics published by Wiley-VCH GmbH.

A Review of mRNA Vaccines with the Aid of Lipid Nanoparticles

This review article highlights the importance of messenger ribonucleic acid (mRNA) vaccines and how it has been developed to fight against various diseases such as, human immunodeficiency virus (HIV), rabies, cancer treatments, and coronavirus (Covid-19). During the past two years, covid-19 has become a worldwide pandemic, and the mRNA has played a major role in the manufacturing of its vaccine. We have highlighted the technology behind the development of mRNA vaccine, synthesis, and working of the lipid nanoparticles (LNPs). This mRNA vaccine produces a duplicate of a molecule that corresponds to a viral protein for producing an immune response, and these are given to us in a series of shots designed to protect us from developing a disease. The LNPs which carry the mRNA protein prevent the degradation of it and maintain more constant serum levels. In addition, this review article specifically mentions HIV, rabies, cancer, covid-19 and how these are important in the treatment of these diseases. This review article further highlights the mRNA vaccines for the survival of human beings against various deadly diseases in the near future. © 2023, The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

Influence of the COVID-19 pandemic on dog ownership and rabies vaccination in Metropolitan Lima.

The aim of this study was to determine the possible influence of the COVID-19 pandemic on dog ownership and anti-rabies vaccination practices in Metropolitan Lima (Peru), taking as a source of information the National Survey of Budgetary Programmes (ENAPRES) carried out by the Instituto Nacional de Estadistica e Informatica (INEI) in the period 2017-2021. The proportion of respondents who owned at least one dog per household had an increasing trend, reaching the highest proportions in the pandemic years (2020: 47.5%;2021: 50.8%). The districts of Lima Sur and Lima Centro presented the highest (52.1-58%) and lowest (31.6-42.4%) proportion of respondents with dogs, respectively. According to the socioeconomic stratum (ESE), dog ownership had an inverse relationship (rs=-0.95), with a higher proportion in sector E (51.5-60.7%) and lower in sector A (32.5-43.1%). The proportion of vaccinated animals had a decreasing trend, reaching the lowest coverage during the pandemic years (2020: 84.8%;2021: 82.4%). The highest proportion of vaccinated dogs was found in Lima Centro (88.1-95.9%). According to ESE, the relationship was direct (rs=0.813). The highest proportion of vaccinated animals during the pre-pandemic and pandemic years occurred in ESE A (90.3-95%) and B (87.8-94.8%). In all the years of the study, the lowest proportions of vaccinated animals were in ESE E (75-80.2%). The study shows that dog ownership and rabies vaccination coverage were affected by the COVID-19 pandemic. The results can be used to assess the sanitary measures implemented to keep the capital free of urban rabies.Copyright © 2023 Universidad Nacional Mayor de San Marcos. All rights reserved.

It's Worth a Shot

The presentation contained information about the virus, how it spreads, the vaccine, who should and should not take it, when it is recommended to be taken, how it invokes an immune response on a cellular level, and what role protein synthesis plays in the vaccine. Students and their partners were given one of seven viruses to research: measles, mumps, rubella, influenza, hepatitis B, rabies, or COVID-19. Students researched the disease and its vaccine type using credible sources, such as the Centers for Disease Control and Prevention (CDC), the World Health Organization (WHO), Johns Hopkins University, etc. Students answered the following questions: * How does the virus spread? * What are the symptoms of the virus? * How common is the virus? (statistical number) * What does the virus look like? (include picture with antigens shown) * When is the vaccine recommended by the CDC? * How often does the booster for the vaccine need to be taken? * Who should not receive the vaccine? * How does the vaccine work on a cellular level? (Be specific about the type of vaccine and how it invokes an immune response) * What role does protein synthesis play in the vaccine? * What is the vaccine efficacy or effectiveness? * Does the vaccine do any of the following: * Change the host cell's DNA? * Give the person the disease?

Monoclonal antibodies for prophylaxis and therapy of respiratory syncytial virus, SARS-CoV-2, human immunodeficiency virus, rabies and bacterial infections: an update from the World Association of Infectious Diseases and Immunological Disorders and the Italian Society of Antinfective Therapy.

Monoclonal antibodies (mABs) are safe and effective proteins produced in laboratory that may be used to target a single epitope of a highly conserved protein of a virus or a bacterial pathogen. For this purpose, the epitope is selected among those that play the major role as targets for prevention of infection or tissue damage. In this paper, characteristics of the most important mABs that have been licensed and used or are in advanced stages of development for use in prophylaxis and therapy of infectious diseases are discussed. We showed that a great number of mABs effective against virus or bacterial infections have been developed, although only in a small number of cases these are licensed for use in clinical practice and have reached the market. Although some examples of therapeutic efficacy have been shown, not unlike more traditional antiviral or antibacterial treatments, their efficacy is significantly greater in prophylaxis or early post-exposure treatment. Although in many cases the use of vaccines is more effective and cost-effective than that of mABs, for many infectious diseases no vaccines have yet been developed and licensed. Furthermore, in emergency situations, like in epidemics or pandemics, the availability of mABs can be an attractive adjunct to our armament to reduce the impact. Finally, the availability of mABs against bacteria can be an important alternative, when multidrug-resistant strains are involved.

Organ transplantation and vaccination

Organ transplant recipients are at a high risk of infection with high hospitalization rate, critical rate and fatality, due to low immune function caused by taking immunosuppressants for a period of long time after organ transplantation. Currently, vaccination is recognized as an effective approach to prevent infection. Organ transplant recipients may be vaccinated according to individual conditions. However, the sensitivity to vaccines may decline in organ transplant recipients. The types, methods and timing of vaccination have constantly been the hot spots of clinical trials. In this article, the general principles, specific vaccines and SARS-CoV-2 vaccines of vaccination in organ transplant recipients were briefly reviewed, aiming to provide reference for the vaccination of organ transplant recipients. Moreover, current status of SARS-CoV-2 vaccination for organ transplant recipients was illustrated under the global outbreak of novel coronavirus pneumonia pandemic.Copyright © 2022 Journal of Zhongshan University. All Rights Reserved.

NIH restarts halted bat virus grant

In January, a federal audit found that EcoHealth had misreported nearly $90,000 in expenses for several grants dating to 2014 and that NIH had erred by not justifying its termination (later changed to a suspension) of the 2019 grant. Three years after then-President Donald Trump pressured the U.S. National Institutes of Health (NIH) to shut down a research grant to a group studying how bat coronaviruses jump to people, the agency has restarted the award. [Extracted from the article] Copyright of Science is the property of American Association for the Advancement of Science and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

Overview on Mrna Vaccines Beyond Covid-19

COVID-19 mRNA vaccines: COVID-19 pandemic has made an extraordinary impact on global vaccine technology platform developments. Never in human history have there at least 6 vaccine platforms including: inactivated, protein subunit, VLP and other 3 new platforms i.e., mRNA, viral vector, and DNA, with more than 160 vaccine candidates being developed and tested in clinical trials. Nonetheless, among these several vaccine platforms, mRNA vaccine has been proven to be one of the most effective vaccines against COVID-19. There are two mRNA vaccines authorized for emergency use within a year and currently more than 20 mRNA vaccines are in clinical trials. The main advantages of mRNA vaccines are that they are speedily to design and develop, induce strong antibody and T-cell responses, manufacturing faster and at a lower cost. However, one of the major limitations is that it must be stored in cold temperatures. Currently more than billion doses of COVID-19 mRNA vaccines have been given globally. mRNA vaccines will be a key platform for next pandemics preparedness, it is therefore establishing this platform in various regions and LMICs is critical. Beyond COVID-19: A number of viral and cancer mRNA vaccines have been developing even before COVID-19. At least 12 mRNA vaccines against various infectious diseases are now in clinical evaluation, including Chikungunya virus, Cytomegalovirus, Epstein-Barr virus, Human metapneumovirus and parainfluenza virus type3, HIV, Influenza, Nipah, Rabies, Lasa, RSV, Zika, Varicella-zoster virus. Only few are entering phase 3 such as a CMV vaccine, RSV, seasonal influenza. Current mRNA cancer vaccines development, including brain, breast, melanoma, esophagus, lung, ovarian, prostate and solid tumors. Most are aimed for personalized therapy. By 2023, at least 1 viral mRNA vaccine may get approval, whereas a cancer vaccine might take much longer time. Nevertheless, the remaining challenge at the global level is how to truly overcome the vaccine inequity issues in a sustainable way.Copyright © 2023

Rabies in a postpandemic world: resilient reservoirs, redoubtable riposte, recurrent roadblocks, and resolute recidivism.

Rabies is an ancient disease. Two centuries since Pasteur, fundamental progress occurred in virology, vaccinology, and diagnostics-and an understanding of pathobiology and epizootiology of rabies in testament to One Health-before common terminological coinage. Prevention, control, selective elimination, and even the unthinkable-occasional treatment-of this zoonosis dawned by the twenty-first century. However, in contrast to smallpox and rinderpest, eradication is a wishful misnomer applied to rabies, particularly post-COVID-19 pandemic. Reasons are minion. Polyhostality encompasses bats and mesocarnivores, but other mammals represent a diverse spectrum of potential hosts. While rabies virus is the classical member of the genus, other species of lyssaviruses also cause the disease. Some reservoirs remain cryptic. Although global, this viral encephalitis is untreatable and often ignored. As with other neglected diseases, laboratory-based surveillance falls short of the notifiable ideal, especially in lower- and middle-income countries. Calculation of actual burden defaults to a flux within broad health economic models. Competing priorities, lack of defined, long-term international donors, and shrinking local champions challenge human prophylaxis and mass dog vaccination toward targets of 2030 for even canine rabies impacts. For prevention, all licensed vaccines are delivered to the individual, whether parenteral or oral-essentially 'one and done'. Exploiting mammalian social behaviors, future 'spreadable vaccines' might increase the proportion of immunized hosts per unit effort. However, the release of replication-competent, genetically modified organisms selectively engineered to spread intentionally throughout a population raises significant biological, ethical, and regulatory issues in need of broader, transdisciplinary discourse. How this rather curious idea will evolve toward actual unconventional prevention, control, or elimination in the near term remains debatable. In the interim, more precise terminology and realistic expectations serve as the norm for diverse, collective constituents to maintain progress in the field.

Trend Analysis of Animal Bite Cases: A Retrospective Study at Anti-Rabies Clinic of a Tertiary Care Hospital of Kashmir

Background: Rabies which is 100 fetal but preventable is caused by bite of rabid animals particularly dogs. Animal bites cases are major public health problem in India and also in the UT of Jammu & Kashmir. Objective(s): To study the trend and seasonal Variation of animal bite cases attending the Anti Rabies clinic (from 2009 to 2022), run by Department of Community Medicine, Government Medical College Srinagar at SMHS Hospital. Material(s) and Method(s): The retrospective Cross sectional study conducted at Anti-Rabies Clinic of SMHS Hospital, a tertiary care associated Hospital of Government Medical College Srinagar. Data was collected from the record of Animal bite register at Anti rabies clinic after proper permission from the incharge of the clinic. Data was entered and analyzed on Excel soft ware. Result(s): More than 70,000 number of animal bites cases were reported at the Anti-Rabies clinic from the year 2009 to 2022. there has been a rise of cases from the year 2009 to 2018 with a slight decrease in the year 2019-20. About 97% of all animal bites were dog bites. Majority of the cases (>60%) were category of three (3) exposure. One year analysis for seasonal variation shows that incidence was more in March and May-June. Conclusion(s): the present study showed that animal bites cases were rising with little decrease in the year 2019-20 as may be due to lesser animal human interaction due to Covid-19 restrictions. Keeping in view the present trend it is expected that the Animal bite cases will show rising trend in coming years. Multidisciplinary approach is advocated to control the increasing trend.

Design and characterization of chimeric Rabies-SARS-CoV-2 virus-like particles for vaccine purposes.

Due to the high number of doses required to achieve adequate coverage in the context of COVID-19 pandemics, there is a great need for novel vaccine developments. In this field, there have been research approaches that focused on the production of SARS-CoV-2 virus-like particles. These are promising vaccine candidates as their structure is similar to that of native virions but they lack the genome, constituting a biosafe alternative. In order to produce these structures using mammal cells, it has been established that all four structural proteins must be expressed. Here we report the generation and characterization of a novel chimeric virus-like particle (VLP) that can be produced by the expression of a single novel fusion protein that contains SARS-CoV-2 spike (S) ectodomain fused to rabies glycoprotein membrane anchoring region in HEK293 cells. This protein is structurally similar to native S and can autonomously bud forming enveloped VLPs that resemble native virions both in size and in morphology, displaying S ectodomain and receptor binding domain (RBD) on their surface. As a proof of concept, we analyzed the immunogenicity of this vaccine candidate in mice and confirmed the generation of anti-S, anti-RBD, and neutralizing antibodies. KEY POINTS: • A novel fusion rabies glycoprotein containing S ectodomain was designed. • Fusion protein formed cVLPs that were morphologically similar to SARS-CoV-2 virions. • cVLPs induced anti-S, anti-RBD, and neutralizing antibodies in mice.

Biosafety Practices When Working with Bats: A Guide to Field Research Considerations.

Introduction: Field work with bats is an important contribution to many areas of research in environmental biology and ecology, as well as microbiology. Work with bats poses hazards such as bites and scratches, and the potential for exposure to infectious pathogens such as rabies virus. It also exposes researchers to many other potential hazards inherent to field work, such as environmental conditions, delayed emergency responses, or challenging work conditions. Methods: This article discusses the considerations for a thorough risk assessment process around field work with bats, pre- and post-occupational health considerations, and delves into specific considerations for areas related to biosafety concerns-training, personal protective equipment, safety consideration in field methods, decontamination, and waste. It also touches on related legal and ethical issues that sit outside the realm of biosafety, but which must be addressed during the planning process. Discussion: Although the focal point of this article is bat field work located in northern and central America, the principles and practices discussed here are applicable to bat work elsewhere, as well as to field work with other animal species, and should promote careful considerations of how to safely conduct field work to protect both researchers and animals.

Infectious disease Roundup 2022

This paper describes the epidemiology, prevalence, transmission, prevention and control of some infectious diseases in companion animals, livestock, wild animals and humans in Ontario, Canada, in 2022, including SARS-CoV-2;Echinococcus multilocularis, Leishmania spp. and SARS-CoV-2;antimicrobial stewardship resources;2 cases of rabid dogs imported from Iran (July 2021 and January 2022);prevalence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriacea, Dirofilaria immitis, Brucella canis, canine parainfluenza and adeno- and herpes viruses in dogs recently imported from Asia;Paragonimus kellicotti lung flukes and Streptococcus equi subsp. zooepidemicus in dogs;African swine fever in pet pigs, backyard pigs and wild pigs and blastomycosis in dogs and humans.

Mad Dogs and Other New Yorkers: Rabies, Medicine, and Society in an American Metropolis, 1840-1920. Jessica Wang

I greatly admire how Wang covers shifting medical and popular knowledge around rabies, illustrating how different and conflicting knowledges structured responses to the threat of mad dogs at the individual, social, and governmental levels. Rabies was never as common or as deadly as this pandemic, but fear of the disease shaped lives and public health policy in New York City in countless ways between 1840 and 1920. Wang did not write for this moment, but the book has much to offer to students and scholars trying to make sense of a multitude of issues surrounding Covid-19 and public health. [Extracted from the article] Copyright of Journal of the History of Medicine & Allied Sciences is the property of Oxford University Press / USA and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full . (Copyright applies to all s.)

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.

Construction and immunogenicity of recombinant rabies virus expressing S gene of SARS-CoV-2

[Background] The coronavirus disease 2019（COVID-19） pandemic has lasted for nearly three years in the globe, which has not only caused serious harm to humans but also affected companion animals. The COVID-19 vaccines for human have been used globally, while those for animals are rarely reported. [Objective] To develop a bivalent vaccine against both severe acute respiratory syndrome coronavirus 2（SARS-CoV-2） and rabies virus（RABV） for animal use. [Methods] We cloned the S and S1 genes of SARS-CoV-2 into the region between G and L genes of the attenuated RABV vaccine strain rHEP-Flury to construct the recombinant plasmids pHEP-nCOV-S and pHEP-nCOV-S1, respectively.The two plasmids were respectively co-transfected into BHK-21 cells with the helper plasmids and finally the recombinant viruses rHEP-nCOV-S and rHEP-nCOV-S1 were rescued. The recombinant viruses were confirmed by RT-PCR and direct fluorescent antibody staining against RABV N protein.Western blotting was employed to detect the expression of S and S1 proteins in the cells infected with the recombinant viruses. The growth curves, pathogenicity, and immunogenicity of recombinant viruses were confirmed in NA cells and mice. [Results] The rescued recombinant viruses rHEP-nCOV-S and rHEP-nCOV-S1 respectively carrying the S and S1 genes of SARS-CoV-2 were confirmed by direct fluorescent antibody assay based on the green fluorescence from the supernatants 7 days post infection.rHEP-nCOV-S1 rather than rHEP-nCOV-S showed stronger proliferation and diffusion abilities than the parental virus rHEP-Flury in NA cells. The specific bands at 72 kDa and 144 kDa in the Western blotting confirmed the efficient expression of S and S1 in the recombinant viruses, respectively. The mice vaccinated with the recombinant viruses did not show significant changes in the body weight compared with those vaccinated with rHEP-Flury, and the recombinant viruses induced the production of neutralizing antibody against RABV in mice. [Conclusion] The production of the recombinant RABV carrying the S/S1 gene of SARS-CoV-2 provides a foundation for the development of the bivalent vaccine against both SARS-CoV-2 and rabies virus for animal use.

Campus travel health services

Travel and students are inextricably linked. The college years are a time when students want to explore the unfamiliar and learn more about the outside world. The benefits of travel are enormous and something any campus would want to encourage. At the same time, however, colleges have a responsibility to protect the health and safety of students as well as the broader community from any negative consequences of travel. It can be quite challenging to develop travel health programs as various models exist and planning requires addressing issues such as staffing levels and training, budget, coordination with various stakeholders, and community resources. Providing appropriate pre- and post-travel care mandates a comprehensive risk analysis and evidenced-based risk mitigation strategies performed by trained travel health staff. © Springer Nature Switzerland AG 2021.

Time series analysis of animal bite cases attending anti-rabies clinic.

Background: Rabies is a disease transmitted mostly through animal bites in humans, and seasonal variation in animal bites has been reported by different studies. There has been no study in India using time series analysis for studying monthly variation in animal bite cases. Aim: (a) To find out long-term trends and monthly variations in new animal bite cases. (b) To make projections for new animal bite cases. (c) To find out the difference between actual and projected new animal bite cases following the COVID-19 pandemic. Methodology: A retrolective, record-based study was conducted in a tertiary care facility, Jaipur, and data of new Category II and Category III animal bite cases were taken from January 2007 to December 2021. A multiplicative model was used for conducting time series analysis. The projected monthly number of cases was estimated using the line of best fit based on the least square method. Result: An increasing trend in the annual number of animal bite cases was observed from 7,982 in 2007 to 10,134 in 2019. The monthly index was lowest for the months July to November (0.88 to 0.95), peaked in January (1.14), remained higher from January to June, and fell in July (0.95). The monthly number of new animal bite cases from April 2020 to December 2021 was significantly lower than the projected number (P-value < 0.001). Conclusion: Because the monthly index of animal bite cases was high from January onward, information education and communication (IEC) activities should be increased in the preceding months (November onward) for making people aware of immediate care to be provided to animal bite cases and seek prompt medical care.

Increase in rabies cases during COVID-19 pandemic: Is there a connection?

Increase in rabies cases during COVID-19 pandemic: Is there a connection?