Innovation-driven trend shaping COVID-19 vaccine development in China / 医学前沿

Confronted with the Coronavirus disease 2019 (COVID-19) pandemic, China has become an asset in tackling the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission and mutation, with several innovative platforms, which provides various technical means in this persisting combat. Derived from collaborated researches, vaccines based on the spike protein of SARS-CoV-2 or inactivated whole virus are a cornerstone of the public health response to COVID-19. Herein, we outline representative vaccines in multiple routes, while the merits and plights of the existing vaccine strategies are also summarized. Likewise, new technologies may provide more potent or broader immunity and will contribute to fight against hypermutated SARS-CoV-2 variants. All in all, with the ultimate aim of delivering robust and durable protection that is resilient to emerging infectious disease, alongside the traditional routes, the discovery of innovative approach to developing effective vaccines based on virus properties remains our top priority.

Advances of human oral viral vaccine development / 生物工程学报

Development of a vaccine that can simultaneously induce effective mucosal immunity and systemic immunity is an ideal goal to prevent mucosal pathogenic infections. The digestive tract has many sites for inducing mucosal immunity, including the mouth, stomach and small intestine. An ideal oral viral vaccine can not only induce better local and distal mucosal immunity, but also produce better systemic immunity. The oral viral vaccine has also attracted much attention because of its painless vaccination, self-administration and other advantages. Due to the complexity of human digestive tract environment and mucosal immunity, only three oral attenuated live vaccines have been successfully marketed for human use. This review summarizes the characteristics of gastrointestinal mucosal immunity, the current types and research status of oral viral vaccines, and the challenges faced by oral viral vaccines, with the hope to facilitate the research and development of oral viral vaccines for human use in China.

A review of the recent advances on Lassa fever with special reference to molecular epidemiology and progress in vaccine development

Lassa fever, a viral hemorrhagic fever caused by the Lassa virus (LASV), is endemic in West Africa and is associated with high morbidity and mortality. At least three of the four proposed seven lineages of LASV are found in Nigeria, where the multimammate rat, Mastomys natalensis, serves as the primary reservoir. Endemic countries report approximately 200,000 infections and 5,000 deaths annually, with Nigeria experiencing thousands of infections and hundreds of deaths including healthcare workers. The aim of this review is to provide scientific information for better understanding of the evolutionary biology, molecular epidemiology, pathogenesis, diagnosis, and prevention of Lassa fever in Nigeria and other endemic regions worldwide, which can lead to improved control efforts and reduce morbidity and mortality from recurrent epidemics. To achieve this aim, observational studies such as case series, cross-sectional and cohort studies published between December 2017 and September 2022 were searched for on various online databases including Google Scholar, Africa Journals Online (AJOL), Research Gates, PubMed, PMIC, NCDC, and WHO websites. Although the origin and evolutionary history, and the transmission dynamics of Lassa virus have been revealed through recent. molecular epidemiological studies, the factors that drive the evolution of the virus remain unclear. Genetic changes in the viral genome may have enabled the virus to adapt to humans. Diagnosis of Lassa fever has also advanced from basic serological tests to more sophisticated methods such as quantitative real time polymerase chain reaction (qRT-PCR) and sequencing, which are particularly useful for identifying outbreak strains. Several vaccines, including recombinant vesicular stomatitis virus (rVSV), virus-like particle (VLP), and DNA-based vaccines, have shown promise in animal models and some have progressed to phase 2 clinical trials. Preventing and controlling Lassa fever is critical to safeguard the health and well-being of affected communities. Effective measures such as rodent control, improved sanitation, and early detection and isolation of infected individuals are essential for reducing transmission. Ongoing research into the genetic and ecological factors that drive the evolution of Lassa virus is necessary to reduce the impacts of Lassa fever.

A covid-19 como um analisador do sofrimento de enfermeiras: um ensaio teórico / Covid-19 as a suffering analyzer for female nurses: a theoretical essay / El covid-19 como analizador de sufrimiento de enfermeras: un ensayo teórico

Este ensaio propõe que a Covid-19 pode operar como um analisador, dentro da perspectiva da análise institucional, iluminando um determinado modo de organização social que promove profundas desigualdades e ameaça a vida em diversos níveis e revelando as condições sociais, institucionais e políticas de produção de sofrimento no corpo profissional de Enfermagem. A pandemia desvelou um conjunto de marcas relacionadas à profissão, agravadas pela crise sanitária, reforçando a naturalização das relações de cuidado atribuídas ao feminino, bem como um conjunto de clivagens e hierarquias internas à profissão a partir da sinergia de marcadores da diferença, como gênero, cor/raça, classe e geração. Além disso, este trabalho mostra a presença de uma necropolítica nas respostas à pandemia que banaliza a vida e permite morrer determinados grupos sociais. A ideia de "profissionais de linha de frente" é criticada em suas metáforas bélicas, mas tomada como figura de linguagem em sua potência para afirmar que existem corpos que, pelas marcas sociais e históricas e pela interdependência do cuidado, são mais presentes e exigidos e, portanto, mais vulneráveis à doença e ao sofrimento dela decorrente.(AU)

The essay proposes that Covid-19 can operate as an analyzer, within the perspective of institutional analysis, illuminating a certain mode of social organization that promotes profound inequalities and threatens life at various levels, revealing the social, institutional and political conditions for the production of suffering in the professional nursing body. The pandemic would unveil a set of marks related to the profession, aggravated by the sanitary crisis, reinforcing the naturalization of the care relations attributed to the feminine, as well as a set of cleavages and internal hierarchies to the profession from the synergy of markers of difference as gender, color/race, class and generation. The work shows the presence of necropolitics in responses to the pandemic, which trivializes life and allows certain social groups to die. The idea of "front-line professionals" is criticized in its war metaphors, but taken as a figure of speech in its potency to affirm that there are bodies that by social and historical marks, and by the interdependence of care, are more present and demanded, and therefore more vulnerable to disease and the resulting suffering.(AU)

El ensayo propone que el Covid-19 puede funcionar como analizador, desde la perspectiva del análisis institucional, revelando las condiciones sociales, institucionales y políticas de producción de sufrimiento de enfermeras. La pandemia revela algunas marcas relacionadas con la profesión, agravadas por la crisis de salud, reforzando la naturalización de la atribución del cuidado a lo femenino y un conjunto de jerarquías internas de la profesión. El trabajo también muestra la presencia de una necropolítica en las respuestas a la pandemia. La idea de "profesionales de primera línea" es criticada, pero tomada como una figura del lenguaje en su potencia para afirmar que hay cuerpos que, por las marcas sociales e históricas y por la interdependencia del cuidado, están más presentes y demandados, y por lo tanto más vulnerables a la enfermedad.(AU)

Protocolo de Revisão de Escopo: a experiência internacional no desenvolvimento e produção de vacina para COVID-19 / Protocol scoping review: the international experience in vaccine development and production for COVID-19

Este protocolo teve como objetivo estruturar as etapas de elaboração de um Scoping Review que pretende estudar as experiências de desenvolvimento e produção de vacinas em 5 países selecionados, comparando com o Brasil. Sendo assim, a introdução buscou contextualizar a questão de desenvolvimento e produção de vacinas no mundo. Posteriormente, foi apresentado o método do trabalho que, neste caso perpassa por uma explanação da escolha prévia dos 5 países selecionados, além de uma busca em 5 repositórios, seguida de busca manual. A pergunta de pesquisa e as palavras chaves foram apresentadas em conjunto com descrição dos critérios de inclusão e exclusão, que levaram a uma seleção final de 25 documentos completos. Por fim, foram apresentados os resultados esperados, quanto ao que se espera encontrar na análise de atores e ações realizadas nos países investigados

This protocol aimed to structure the steps of a Scoping Review that intends to study the experiences of vaccine development and production in 5 selected countries, comparing with Brazil. Thus, the introduction sought to contextualize the issue of vaccine development and production in the world. Afterwards, the method of the work was presented, which in this case involves an explanation of the previous choice of the 5 selected countries, besides a search in 5 repositories, followed by a manual search. The research question and the key words were presented together with a narrative of the inclusion and exclusion criteria, which led to a total selection of 25 full documents. Finally, the expected results were presented, which indicates what is expected to be found in the analysis of actors and actions taken in the countries in question

Producción de vacunas en el antiguo Instituto Bacteriológico de Chile / Vaccine production at the ancient Bacteriological Institute of Chile

Se relata el nacimiento, auge y decadencia, de la producción de vacunas en el antiguo Instituto Bacteriológico de Chile, desde su fundación en 1929 hasta su fin en 1980, por boca de quien fuera por diecisiete años primero encargado de la fabricación de vacunas bacterianas y luego director de la institución. Las vicisitudes de la vacuna BCG, la introducción del toxoide tetánico, el fin de la vacuna antivariólica y el triunfo de vacuna antirrábica de Fuenzalida y Palacios, se narran a menudo con comentarios de quienes participaron en estos hechos.

The birth, rise and decline, of vaccine production at the Bacteriological Institute of Chile is recounted by mouth of who was for seventeen years first in charge of manufacturing and then director of the institution. The vicissitudes of the BCG vaccine, the introduction of tetanus toxoid, the end of smallpox vaccine, and the triumph of the rabies vaccine are often related with comments from those who participated in the events.

A review on risk assessment of formulation development and technology transfer of COVID-19 vaccines / Una revisión sobre la evaluación de riesgos del desarrollo de formulaciones y la transferencia de tecnología de las vacunas COVID-19

Background: COVID-19 pandemic situation made the pharmaceutical companies develop the vaccine with different formulations in a short period. Objectives: The main objective of the review is to focus on different types of vaccine formulations available globally and the importance of technology transfer in vaccine development associated with potential risks. Results: Research on vaccine development led to various types of vaccines, such as Inactivated vaccines, Live Attenuated vaccines, Ribonucleic acid (RNA) and Deoxyribonucleic acid (DNA) vaccines, viral vector vaccines, and Protein Subunit Vaccines for COVID-19. But the process of vaccine development and technology transfer is lined with various risks and challenges. Through risk assessment, we found some major potential risks involved in product development; this leads to a smoother and more efficient method to develop safe vaccines available for public health. Conclusions: This review will explain the significance of technology collaboration for the faster development of various formulations of vaccines globally

Antecedentes: La situación de pandemia de COVID-19 hizo que las empresas farmacéuticas desarrollaran la vacuna con diferentes formulaciones en un corto período. Objetivos: El objetivo principal de la revisión es centrarse en los diferentes tipos de formulaciones de vacunas disponibles a nivel mundial y la importancia de la transferencia de tecnología en el desarrollo de vacunas asociado con los riesgos potenciales. Resultados: La investigación sobre el desarrollo de vacunas condujo al desarrollo de varios tipos de vacunas, como vacunas inactivadas, vacunas vivas atenuadas, vacunas de ácido ribonucleico (ARN) y ácido desoxirribonucleico (ADN), vacunas de vectores virales y vacunas de subunidades de proteínas para COVID-19. Pero el proceso de desarrollo de vacunas y transferencia de tecnología está lleno de varios riesgos y desafíos. A través de la evaluación de riesgos, encontramos algunos riesgos potenciales importantes involucrados en el desarrollo de productos, lo que conduce a un método más fluido y eficiente para desarrollar vacunas seguras disponibles para la salud pública. Conclusiones: Esta revisión dará una idea de la importancia de la colaboración tecnológica para el desarrollo más rápido de varias formulaciones de vacunas a nivel mundial

Strategies for syphilis vaccine development

Research to identify a syphilis vaccine began shortly after the isolation of the first Treponema pallidum subspecies pallidum (T. pallidum) strain in 1912 by Nichols and Hough and the identification of several possible animal models for the infection, with the rabbit being the best one. During the century following T. pallidum isolation, none of the numerous immunization/challenge experiments performed with preparations ranging from whole-inactivated T. pallidum cells to recombinant proteins yielded an effective vaccine, and the search for a vaccine languished. Recently, however, scientific communities have experienced a resurgence in interest in developing a syphilis vaccine due to 1. the awareness that syphilis constitutes a tremendous burden for maternal health, particularly in low- and middle-income nations; 2. the improved understanding of the immunological processes leading to pathogen clearance during natural infection and of the mechanisms this pathogen developed to persist in the host; 3. the availability of a near-complete list of T. pallidum genes encoding putative surface-exposed antigens, which represent the most likely vaccine candidates; and, last but not least, 4. the effort made to expand the knowledge on the genetic and antigenic diversity of these vaccine candidates in strains circulating worldwide. Thus far, the most recent vaccine designs based on a subset of the pathogen's surface-exposed antigens have provided immunized rabbits with a significant but incomplete protection upon infectious challenge. Nonetheless, the outcomes of these experiments help investigators refine strategies to achieve a formulation with the highest chances of moving from preclinical experimental settings to clinical trials. This editorial focuses on a subset of the strategies currently believed to be essential for vaccine development, namely, the improvement of our still limited understanding of the genomic diversity in T. pallidum strains from diverse geographical locations through the collection and isolation of modern syphilis strains and the identification of protective epitopes in potential vaccine targets by evaluating the ability of monoclonal antibodies to bind the target antigen and facilitate pathogen clearance. The use of genetic engineering of the syphilis spirochete to identify target surface proteins with an essential or near-essential role in T. pallidum biology to target in immunization/challenge experiments is also discussed.

Caracterização funcional de proteínas hipotéticas de Leptospira interrogans como adesinas e potenciais antígenos vacinais e para diagnóstico / Functional characterization of hypothetical proteins in Leptospira interrogans as adhesins and potential vaccine and diagnostic antigens

Leptospira spp. constitui um grupo de bactérias espiroquetas gram-negativas englobando espécies saprofíticas, intermediárias e patogênicas, sendo as últimas agentes causadores da leptospirose, doença zoonótica de alcance mundial e endêmica em regiões tropicais em desenvolvimento. O crescente número de espécies identificadas de leptospiras destaca ainda mais sua diversidade genética e mecanismos de virulência únicos, muitos deles com função ainda desconhecida. Esforços para o desenvolvimento de novas vacinas com proteção cruzada e efeito duradouro revelaram possíveis candidatos vacinais que necessitam ser adequadamente validados, sendo assim, há ainda uma urgente necessidade de uma vacina universal contra a leptospirose capaz de controlar e reduzir os surtos cada vez mais frequentes da doença. Adesinas são importantes fatores de virulência em diversos patógenos, constituindo antígenos promissores para o desenvolvimento de vacinas contra a leptospirose, assim como para o desenvolvimento de métodos diagnósticos mais rápidos e precisos. Previamente, foram identificadas três proteínas hipotéticas conservadas em L. interrogans pela técnica de phage display, denominadas arbitrariamente como LepA069, LepA962 e LepA388. A expressão do gene codificador da proteína LepA069 apresentou aumento de aproximadamente 70 % em animais infectados por leptospiras virulentas, representando a primeira evidência funcional desta proteína ainda desconhecida. Porções recombinantes da lipoproteína hipotética LepA962 (LepA962_Nt e LepA962_Phg) foram obtidos, sendo demonstrada a forte interação da proteína LepA962_Phg, contendo a sequência identificada por phage display, com laminina, fibronectina plasmática, colágeno I e fibrinogênio de maneira dose-dependente. Adicionalmente, LepA962_Phg apresentou ligação às células VERO e à sua matriz extracelular secretada, e o soro obtido a partir desta proteína recombinante foi capaz de se ligar à superfície de leptospiras virulentas, indicando que LepA962_Phg pode representar um importante domínio de interação entre as leptospiras e seu hospedeiro. Finalmente, a proteína LepA388 pertencente a uma extensa família de proteínas modificadoras de virulência com função desconhecida (DUF_61), presente apenas nas leptospiras patogênicas mais virulentas, apresentou aumento na expressão de seu gene codificador em animais infectados por leptospiras virulentas de acordo com dados na literatura. Além disso, porções recombinantes da região Nterminal desta proteína apresentaram ligação a laminina, colágenos I e IV, vitronectina e fibronectinas plasmática e celular, principalmente considerando a sequência identificada por phage display. Estes dados reforçam as predições de modelos tridimensionais da proteína LepA388 e de outros membros da família DUF_61, as quais identificam domínios semelhantes a toxinas (como abrina e CARDS) responsáveis pela ligação e internalização celulares nos hospedeiros. Dados recentes sugerem um possível papel citotóxico desempenhado pelas proteínas desta família em leptospiras, as quais podem também ser consideradas potenciais candidatas vacinais e para diagnóstico da leptospirose, devido à sua distribuição restrita em espécies e cepas patogênicas de importância para saúde humana.

Leptospira spp. constitutes a group of gram-negative spirochete bacteria comprising saprophytic, intermediate and pathogenic species, the last being causative agents of leptospirosis, a zoonotic disease of worldwide extent and endemic in developing tropical regions. The growing number of identified leptospiral species further highlights their genetic diversity and unique virulence mechanisms, many of them with unknown function. Efforts to develop new vaccines with cross-protection and long-lasting effect have revealed possible vaccine candidates that need to be properly validated. Therefore, there is still an urgent need for a universal vaccine against leptospirosis capable of controlling and reducing the increasing outbreaks of the disease. Adhesins are important virulence factors in several pathogens, constituting promising antigens for the development of vaccines against leptospirosis, as well as for the development of faster and more accurate diagnostic methods. Previously, three conserved hypothetical proteins in L. interrogans were identified by phage display technique, arbitrarily named as LepA069, LepA962 and LepA388. Expression of the LepA069 encoding gene showed an increase of approximately 70 % in animals infected by virulent leptospires, representing the first functional evidence of this still unknown protein. Recombinant portions of the hypothetical lipoprotein LepA962 (LepA962_Nt and LepA962_Phg) were obtained, demonstrating the strong interaction of the LepA962_Phg protein, containing the sequence identified by phage display, with laminin, plasma fibronectin, collagen I and fibrinogen in a dose-dependent manner. Furthermore, LepA962_Phg showed binding to VERO cells and its secreted extracellular matrix, and the serum obtained from this recombinant protein was able to bind to the surface of virulent leptospires, indicating that LepA962_Phg may represent an important domain of interaction between leptospires and its host. Finally, LepA388 protein belonging to an extensive family of virulence modifying proteins with unknown function (DUF_61), present only in the most virulent pathogenic leptospires, showed an increase in the expression of its encoding gene in animals infected by virulent leptospires according to data in literature. Moreover, recombinant portions of the N-terminal region of this protein showed binding to laminin, collagens I and IV, vitronectin and plasma and cell fibronectins, especially considering the sequence identified by phage display. These data support the predictions of three-dimensional models of the LepA388 protein and other members of the DUF_61 family, which identify toxin-like domains (such as abrin and CARDS) responsible for cellular binding and internalization in hosts. Recent data suggest a possible cytotoxic role played by proteins of this family in leptospires, which can also be considered potential vaccine candidates and antigens for diagnosis, due to their restricted distribution in pathogenic species and strains of importance to human health

Vacinas COVID-19 e reações imunoalérgicas / COVID-19 vaccines and immunoallergic reactions

A avaliação dos riscos e benefícios deve ser realizada para qualquer intervenção preventiva, diagnóstica ou terapêutica em Medicina. As vacinas, assim como qualquer imunobiológico, são consagradas pelas inúmeras vantagens inerentes à proteção da saúde, apesar dos potenciais riscos de eventos adversos que, na imensa maioria das vezes, são raros, leves e controláveis. O desenvolvimento de vacinas contra o novo SARS-CoV-2 representa um dos principais anseios da população mundial e representa extraordinário avanço da Ciência. Pacientes com histórico de alergias graves a algum componente das vacinas ou a uma dose prévia de alguma delas, devem ser avaliados com cautela pelo especialista para decidir se esta deverá ser contraindicada, aplicada com supervisão médica, ou se estará indicado protocolo de dessensibilização.

The assessment of risks and benefits must be carried out for any preventive, diagnostic, or therapeutic intervention in medicine. Vaccines, like any biologic, are recognized for the innumerable advantages in public health, despite the potential risks of adverse events that, in the vast majority of cases, are rare, mild, and controllable. The development of vaccines against the new SARSCoV- 2 represents one of the main wishes of the world population as well as an extraordinary advance in science. Patients with a history of severe allergies to any component of the vaccines or reaction to a previous dose of any of them should be carefully evaluated by the specialist to decide whether vaccination should be contraindicated or administered with medical supervision, or if a desensitization protocol will be indicated.