Vaccine development: Current trends and technologies.

Despite the effectiveness of vaccination in reducing or eradicating diseases caused by pathogens, there remain certain diseases and emerging infections for which developing effective vaccines is inherently challenging. Additionally, developing vaccines for individuals with compromised immune systems or underlying medical conditions presents significant difficulties. As well as traditional vaccine different methods such as inactivated or live attenuated vaccines, viral vector vaccines, and subunit vaccines, emerging non-viral vaccine technologies, including viral-like particle and nanoparticle vaccines, DNA/RNA vaccines, and rational vaccine design, offer new strategies to address the existing challenges in vaccine development. These advancements have also greatly enhanced our understanding of vaccine immunology, which will guide future vaccine development for a broad range of diseases, including rapidly emerging infectious diseases like COVID-19 and diseases that have historically proven resistant to vaccination. This review provides a comprehensive assessment of emerging non-viral vaccine production methods and their application in addressing the fundamental and current challenges in vaccine development.

[Recent advances in the development of vaccines against hemorrhagic fevers caused by arenaviruses]. / Les fièvres hémorragiques causées par les arénavirus : de récentes avancées vaccinales.

Arenaviruses are a global threat, causing thousands of deaths each year in several countries around the world. Despite strong efforts in the development of vaccine candidates, vaccines against Lassa fever or Bolivian and Venezuelan hemorrhagic fevers are yet to be licensed for a use in humans. In this synthesis, we present the arenaviruses causing fatal diseases in humans and the main vaccine candidates that have been developed over the past decades with an emphasis on the measles-Lassa vaccine, the first Lassa vaccine ever tested in humans, and on the MOPEVAC platform that can potentially be used as a pan-arenavirus vaccine platform.

Title: Les fièvres hémorragiques causées par les arénavirus : de récentes avancées vaccinales. Abstract: Le développement de vaccins contre les arénavirus est un enjeu global. En effet, plusieurs milliers de personnes meurent chaque année de la fièvre de Lassa en Afrique occidentale et les virus Machupo, Guanarito ou Chapare continuent de ré-émerger en Amérique du Sud. Pourtant, il n'existe à ce jour aucun vaccin validé pour une utilisation dans l'espèce humaine pour lutter contre ces arénavirus. Dans cette synthèse, nous présentons les différents arénavirus causant des maladies mortelles chez l'espèce humaine et les principaux candidats vaccins développés au cours des dernières décennies contre ces virus. Nous décrivons plus particulièrement le vaccin rougeole-Lassa, premier vaccin contre la fièvre de Lassa à avoir été testé dans l'espèce humaine, et la plateforme MOPEVAC qui permet de générer avec succès des vaccins mono- ou multivalents contre potentiellement tous les arénavirus pathogènes connus.

Zika-specific neutralizing antibodies targeting inter-dimer envelope epitopes.

Zika virus (ZIKV) is an emerging pathogen that causes devastating congenital defects. The overlapping epidemiology and immunologic cross-reactivity between ZIKV and dengue virus (DENV) pose complex challenges to vaccine design, given the potential for antibody-dependent enhancement of disease. Therefore, classification of ZIKV-specific antibody targets is of notable value. From a ZIKV-infected rhesus macaque, we identify ZIKV-reactive B cells and isolate potent neutralizing monoclonal antibodies (mAbs) with no cross-reactivity to DENV. We group these mAbs into four distinct antigenic groups targeting ZIKV-specific cross-protomer epitopes on the envelope glycoprotein. Co-crystal structures of representative mAbs in complex with ZIKV envelope glycoprotein reveal envelope-dimer epitope and unique dimer-dimer epitope targeting. All four specificities are serologically identified in convalescent humans following ZIKV infection, and representative mAbs from all four groups protect against ZIKV replication in mice. These results provide key insights into ZIKV-specific antigenicity and have implications for ZIKV vaccine, diagnostic, and therapeutic development.

Molecular characterisation of the current high prevalence of the new CPV-2c variants in the Southern Vietnamese dogs signifies a widespread in the worldwide dog population.

BACKGROUND: Canine parvovirus type 2 (CPV-2) is known as the primary etiological agent cause of acute gastroenteritis, myocarditis and death of canids worldwide. In Vietnam, although CPV-2 infection and its outbreaks are the most important risk factors of the canine's health concern, lack of available information about the molecular epidemiology of the CPV-2. OBJECTIVES: In this study, the complete coding sequences of 10 CPV-2 strains collected from dogs vaccinated with CPV-2 vaccination were analysed to better understand the genomic characteristics of the current circulating CPV-2 in Vietnam. METHODS: Ten CPV-specific PCR-positive rectal swab samples were collected from dogs with acute symptoms of haemorrhagic diarrhoea and vomiting in Vietnam in 2019. The complete coding sequences of these CPV strains were analysed to determine their phylogeny and genetic relationship with other available CPV strains globally. RESULTS: Analysis of the VP2 gene sequences demonstrated that the studied strains belonged to the new CPV-2c variants with the unique mutations at amino acids 5Ala-Gly and 447Iso-Met . Phylogenetic tree analysis indicated that the studied strains share a common evolutionary origin with the current CPV-2c strains circulating in dogs in Asia countries, including China, Thailand, Taiwan and Mongolia, in recent years. Low sequence identity between the studied strains and commercial vaccine strains was observed. CONCLUSIONS: This study provides deep insights into the molecular characteristics, genetic diversity, and evolution of circulating CPV-2 strains in Vietnam. We recommend more studies to estimate the effectiveness of the CPV vaccine and the need to continue developing other effective vaccination essential to better control the widespread of these new CPV-2 variants.

Viral vectored vaccines: design, development, preventive and therapeutic applications in human diseases.

Human diseases, particularly infectious diseases and cancers, pose unprecedented challenges to public health security and the global economy. The development and distribution of novel prophylactic and therapeutic vaccines are the prioritized countermeasures of human disease. Among all vaccine platforms, viral vector vaccines offer distinguished advantages and represent prominent choices for pathogens that have hampered control efforts based on conventional vaccine approaches. Currently, viral vector vaccines remain one of the best strategies for induction of robust humoral and cellular immunity against human diseases. Numerous viruses of different families and origins, including vesicular stomatitis virus, rabies virus, parainfluenza virus, measles virus, Newcastle disease virus, influenza virus, adenovirus and poxvirus, are deemed to be prominent viral vectors that differ in structural characteristics, design strategy, antigen presentation capability, immunogenicity and protective efficacy. This review summarized the overall profile of the design strategies, progress in advance and steps taken to address barriers to the deployment of these viral vector vaccines, simultaneously highlighting their potential for mucosal delivery, therapeutic application in cancer as well as other key aspects concerning the rational application of these viral vector vaccines. Appropriate and accurate technological advances in viral vector vaccines would consolidate their position as a leading approach to accelerate breakthroughs in novel vaccines and facilitate a rapid response to public health emergencies.

Lassa fever vaccine candidates: A scoping review of vaccine clinical trials.

OBJECTIVE: Lassa fever (LF) is caused by a viral pathogen with pandemic potential. LF vaccines have the potential to prevent significant disease in individuals at risk of infection, but no such vaccine has been licensed or authorised for use thus far. We conducted a scoping review to identify and compare registered phase 1, 2 or 3 clinical trials of LF vaccine candidates, and appraise the current trajectory of LF vaccine development. METHOD: We systematically searched 24 trial registries, PubMed, relevant conference abstracts and additional grey literature sources up to 27 October 2022. After extracting key details about each vaccine candidate and each eligible trial, we qualitatively synthesised the evidence. RESULTS: We found that four LF vaccine candidates (INO-4500, MV-LASV, rVSV∆G-LASV-GPC, and EBS-LASV) have entered the clinical stage of assessment. Five phase 1 trials (all focused on healthy adults) and one phase 2 trial (involving a broader age group from 18 months to 70 years) evaluating one of these vaccines have been registered to date. Here, we describe the characteristics of each vaccine candidate and trial and compare them to WHO's target product profile for Lassa vaccines. CONCLUSION: Though LF vaccine development is still in early stages, current progress towards a safe and effective vaccine is encouraging.

Lassa Virus Countermeasures.

Lassa Fever (LF) is a viral hemorrhagic fever endemic in West Africa. LF begins with flu-like symptoms that are difficult to distinguish from other common endemic diseases such as malaria, dengue, and yellow fever making it hard to diagnose clinically. Availability of a rapid diagnostic test and other serological and molecular assays facilitates accurate diagnosis of LF. Lassa virus therapeutics are currently in different stages of preclinical development. Arevirumab, a cocktail of monoclonal antibodies, demonstrates a great safety and efficacy profile in non-human primates. Major efforts have been made in the development of a Lassa virus vaccine. Two vaccine candidates, MeV-NP and pLASV-GPC are undergoing evaluation in phase I clinical trials.

COVID-19: Clinical status of vaccine development to date.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced COVID-19 is a complicated disease. Clinicians are continuously facing difficulties to treat infected patients using the principle of repurposing of drugs as no specific drugs are available to treat COVID-19. To minimize the severity and mortality, global vaccination is the only hope as a potential preventive measure. After a year-long global research and clinical struggle, 165 vaccine candidates have been developed and some are currently still in the pipeline. A total of 28 candidate vaccines have been approved for use and the remainder are in different phases of clinical trials. In this comprehensive report, the authors aim to demonstrate, classify and provide up-to-date clinical trial status of all the vaccines discovered to date and specifically focus on the approved candidates. Finally, the authors specifically focused on the vaccination of different types of medically distinct populations.

SARS-CoV-2 Vaccines: Types, Working Principle, and Its Impact on Thrombosis and Gastrointestinal Disorders.

In the current scenario of the coronavirus pandemic caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), considerable efforts have been made to control the pandemic by the development of a strong immune system through massive vaccination. Just after the discovery of the genetic sequences of SARS-CoV-2, the development of vaccines became the prime focus of scientists around the globe. About 200 SARS-CoV-2 candidate vaccines have already been entered into preclinical and clinical trials. Various traditional and novel approaches are being utilized as a broad range of platforms. Viral vector (replicating and non-replicating), nucleic acid (DNA and RNA), recombinant protein, virus-like particle, peptide, live attenuated virus, an inactivated virus approaches are the prominent attributes of the vaccine development. This review article includes the current knowledge about the platforms used for the development of different vaccines, their working principles, their efficacy, and the impacts of COVID-19 vaccines on thrombosis. We provide a detailed description of the vaccines that are already approved by administrative authorities. Moreover, various strategies utilized in the development of emerging vaccines that are in the trial phases along with their mode of delivery have been discussed along with their effect on thrombosis and gastrointestinal disorders.

Evaluación de riesgo biológico en el control de calidad de vacunas virales / Biological risk evaluation in the quality control of viral vaccines

Las medidas de bioseguridad son el conjunto de conductas mínimas a ser adoptadas, a fin de reducir o eliminar los riesgos para el personal, la comunidad y el medio ambiente. Los laboratorios veterinarios manipulan materiales biológicos que pueden suponer riesgos biológicos tanto para los animales como para el hombre, por lo que los profesionales de estos laboratorios están expuestos a una variedad de riesgos relacionados con su trabajo que pueden afectar su salud. El objetivo de este trabajo fue evaluar el riesgo en el control de calidad de las vacunas virales mediante el uso del método BIOGAVAL, una forma cómoda y fiable de evaluar el riesgo de exposición a agentes biológicos. El estudio se realizó en la Unidad Empresarial de Base Control de la Calidad de la Empresa Productora de Vacunas Virales y Bacterianas el cual pertenece a LABIOFAM. La muestra de estudio estuvo conformada por 18 trabajadores, distribuidos en tres áreas. En los resultados obtenidos para valores superiores a 12 del nivel de acción biológica se requiere la adopción de medidas preventivas para reducir la exposición en el caso de Avulavirus, Pestivirus y Coronavirus, mientras que para Alphavirus se requieren acciones correctoras inmediatas ya que representa una situación de riesgo intolerable(AU)

Biosafety measures are the set of minimum behaviors to be adopted, in order to reduce or eliminate risks to personnel, the community and the environment. Veterinary laboratories handle biological materials that can pose biological risks for both animals and humans, so that professionals in these laboratories are exposed to a variety of risks to their health related to their work. The objective of this work was to evaluate the risk in the quality control of viral vaccines through the use of BIOGAVAL method, a convenient and reliable way to assess the risk of exposure to biological agents. The study was carried out in the Base Business Unit Quality Control of the Production Company of Viral and Bacterial Vaccines which belongs to LABIOFAM. The study sample consisted was 18 workers, dispersed in three areas. For values above 12 of the biological action level, preventive measures are required to reduce exposure to Avulavirus, Pestivirus and Coronavirus, while for Alphavirus immediate corrective measures actions are required as it represents an intolerable risk situation(AU)

[Progress on the development of the SARS-CoV-2 vaccine and antibody drugs].

The raging global epidemic of coronavirus disease 2019 (COVID-19) not only poses a major threat to public health, but also has a huge impact on the global health care system and social and economic development. Therefore, accelerating the development of vaccines and antibody drugs to provide people with effective protection and treatment measures has become the top priority of researchers and medical institutions in the field. At present, several vaccines and antibody drugs targeting SARS-Cov-2 have been in the stage of clinical research or approved for marketing around the world. In this manuscript, we summarized the vaccines and antibody drugs which apply genetic engineering technologies to target spike protein, including subunit vaccines, viral vector vaccines, DNA vaccines, mRNA vaccines, and several neutralizing antibody drugs, and discussed the trends of vaccines and antibody drugs in the future.