Immunogenicity and reactogenicity of heterologous immunization schedules with COVID-19 vaccines: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Data on the immunogenicity and safety of heterologous immunization schedules are inconsistent. This study aimed to evaluate the immunogenicity and safety of homologous and heterologous immunization schedules.@*METHODS@#Multiple databases with relevant studies were searched with an end date of October 31, 2021, and a website including a series of Coronavirus disease 2019 studies was examined for studies before March 31, 2022. Randomized controlled trials (RCTs) that compared different heterologous and homologous regimens among adults that reported immunogenicity and safety outcomes were reviewed. Primary outcomes included neutralizing antibodies against the original strain and serious adverse events (SAEs). A network meta-analysis (NMA) was conducted using a random-effects model.@*RESULTS@#In all, 11 RCTs were included in the systematic review, and nine were ultimately included in the NMA. Among participants who received two doses of CoronaVac, another dose of mRNA or a non-replicating viral vector vaccine resulted in a significantly higher level of neutralizing antibody than a third CoronaVac 600 sino unit (SU); a dose of BNT162b2 induced the highest geometric mean ratio (GMR) of 15.24, 95% confidence interval [CI]: 9.53-24.39. Following one dose of BNT162b2 vaccination, a dose of mRNA-1273 generated a significantly higher level of neutralizing antibody than BNT162b2 alone (GMR = 1.32; 95% CI: 1.06-1.64), NVX-CoV2373 (GMR = 1.60; 95% CI: 1.16-2.21), or ChAdOx1 (GMR = 1.80; 95% CI: 1.25-2.59). Following one dose of ChAdOx1, a dose of mRNA-1273 was also more effective for improving antibody levels than ChAdOx1 (GMR = 11.09; 95% CI: 8.36-14.71) or NVX-CoV2373 (GMR = 2.87; 95% CI: 1.08-3.91). No significant difference in the risk for SAEs was found in any comparisons.@*CONCLUSIONS@#Relative to vaccination with two doses of CoronaVac, a dose of BNT162b2 as a booster substantially enhances immunogenicity reactions and has a relatively acceptable risk for SAEs relative to other vaccines. For primary vaccination, schedules including mRNA vaccines induce a greater immune response. However, the comparatively higher risk for local and systemic adverse events introduced by mRNA vaccines should be noted.@*REGISTRATION@#PROSPERO; https://www.crd.york.ac.uk/PROSPERO/ ; No. CRD42021278149.

A survey of public perception, knowledge and factors influencing COVID-19 vaccine acceptability in five communities in Ghana

Objective: The present study assessed the public's perception and Knowledge about COVID-19 and factors that could affect vaccine acceptability in Ghana. Design: We carried out a cross-sectional population-based study. A structured questionnaire was used to capture data on socio-demographic information, knowledge, and the public's perception of COVID-19 infection, as well as COVID-19 vaccine acceptability from consented participants. Factors affecting vaccine acceptability in Ghana were explored. Robust ordinary least square linear regression analysis was adopted to assess factors associated with vaccine acceptability. Setting: Five communities (Labone, Lartebiorkoshie, Old Fadama, Chorkor, and Ashiyie) in Accra in the Greater Accra district were selected. Participants: WHO modified cluster-sampling method was applied to select households of 997 participants in the five communities. Results: Most respondents were males (57.6%), and the median age of participants was 30 years. The study participants demonstrated a good knowledge of COVID-19 and had high perceptions of the COVID-19 pandemic. The results revealed that the highest educational level, marital status, self-rated Knowledge of COVID-19, Knowledge of COVID-19 definition, Knowledge of COVID-19 symptoms, and perception of the COVID-19 pandemic were significantly associated with vaccine acceptability. Self-reported impact of COVID-19 lockdown/movement restrictions on agriculture and job as a source of livelihood was associated with vaccine acceptability. Conclusion: Higher subjective and objective knowledge of COVID-19 increases vaccine acceptability scores significantly thus, education on COVID-19 and the vaccination against SARS-CoV-2 infection must be intensified to improve vaccine acceptability in Ghana, especially among those with lower educational backgrounds

Vacinas COVID-19 e suas implicações imunológicas: uma revisão de literatura / COVID-19 vaccines and immunological implications: A literature review

A COVID-19 e seus mecanismos imunológicos são, atualmente, temas de grande relevância mundial. Suas manifestações clínicas e as perigosas complicações decorrentes da tempestade de citocinas motivaram a criação de vacinas contra o SARS-CoV-2 em um ritmo acelerado, gerando desconfianças e diferentes níveis de eficácia e segurança. Este estudo trata-se de um artigo de revisão que abordou pesquisas publicadas no período de 2020 e 2021, utilizando as bibliotecas eletrônicas SciELO (Scientific Electronic Library Online), PubMed, LILACS (Literatura Latino-Americana e do Caribe em Ciências da Saúde) e MEDLINE com o rastreamento específico por meio dos seguintes descritores: vacinas COVID-19, SARS-CoV-2, imunologia do COVID-19. Questões como o mecanismo imunológico, eficácia e efeitos adversos das vacinas disponíveis no mercado mundial atual foram amplamente discutidas.

COVID-19 and immunological mechanisms currently are topics of great worldwide relevance. Clinical manifestations and the dangerous complications resulting from a cytokine storm motivated the creation of vaccines against SARS-CoV-2 at an accelerated pace, generating suspicions and different levels of efficacy and safety. This is a review article addressing research published in 2020 and 2021. The electronic libraries SciELO (Scientific Electronic Library Online), PubMed, LILACS (Latin American and Caribbean Literature in Health Sciences), and MEDLINE were used for specific screening with the following descriptors: COVID- 19 vaccines, SARS-CoV-2, immunology of COVID-19. Issues such as the immunological mechanism, efficacy, and adverse effects of vaccines currently available on the world market are widely discussed.

Vacina COVID-19 em pacientes com urticária ­ Posicionamento do Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia (ASBAI) / COVID-19 vaccine in patients with urticaria ­ Position statement of the Scientific Department of Urticaria of the Brazilian Association of Allergy and Immunology (ASBAI)

Com o início do programa de vacinação contra a COVID-19 no Brasil, surgiu uma série de questionamentos relacionados ao uso dos imunizantes em pacientes com doenças imunoalérgicas. Neste documento, o Departamento Científico de Urticária da Associação Brasileira de Alergia e Imunologia (ASBAI) se posiciona revisando as principais dúvidas relacionadas à imunização para COVID-19 em pacientes com urticária.

As the COVID-19 vaccination program started in Brazil, many questions have arisen regarding the use of vaccines in patients with immune-allergic diseases. In this document, the Scientific Department of Urticaria of the Brazilian Association of Allergy and Immunology takes a stand by reviewing the main queries regarding COVID-19 immunization in patients with urticaria.

Vacinas COVID-19 e imunobiológicos / COVID-19 vaccines and immunobiological drugs

Os medicamentos imunobiológicos têm sido frequentemente utilizados no tratamento das doenças alérgicas e de natureza imunológica. Esses agentes regulam a resposta imunológica do tipo 2 nas doenças alérgicas ou atuam em diversas vias de ativação alteradas nos erros inatos da imunidade. Com o surgimento da pandemia COVID-19 um crescente número de pacientes em uso de imunobiológicos para essas condições deverão ser vacinados contra o vírus SARS-CoV-2. Dessa forma, existe a necessidade de avaliar a segurança e eficácia destas vacinas nos pacientes em uso de imunobiológicos para asma, dermatite atópica, rinossinusite crônica com pólipos nasais, urticária crônica e erros inatos da imunidade. Foi realizada uma busca de literatura recente relevante sobre imunobiológicos e vacinas COVID-19 no PubMed. Existe um consenso de manutenção desses agentes durante a pandemia COVID-19, embora nas doenças alérgicas os mesmos devam ser suspensos durante a infecção ativa. Por outro lado, dados disponíveis em relação à segurança e eficácia das vacinas contra a COVID-19 nesse grupo de pacientes são escassos. Existem relatos do uso de outras vacinas inativadas em associação com alguns imunobiológicos demonstrando serem eficazes e seguras. Portanto, considerando o risco potencial da infecção COVID-19, especialmente nos pacientes portadores de erros inatos da imunidade, recomendamos que as vacinas contra a COVID-19 sejam utilizadas nos pacientes em uso de imunobiológicos. Desta forma, existe uma necessidade de estudos que avaliem estas questões haja vista que a terapia com diversos imunobiológicos tem sido amplamente utilizada nos pacientes com doenças alérgicas e de natureza imunológica.

Immunobiological drugs have often been used to treat allergic and immunological diseases. These agents regulate the type 2 immune response in allergic diseases or act on different activation pathways altered in inborn errors of immunity. With the emergence of the COVID-19 pandemic, an increasing number of patients with these conditions using these agents should be vaccinated against the SARS-CoV-2 virus. Thus, there is a need to evaluate the safety and efficacy of these vaccines in patients using biologics for asthma, atopic dermatitis, chronic rhinosinusitis with nasal polyps, chronic urticaria, and inborn errors of immunity. A search for relevant recent literature on biologics and COVID-19 vaccines was conducted on PubMed. There is a consensus on maintaining the use of these agents during the COVID-19 pandemic, although in allergic diseases they must be suspended during active infection. Conversely, the available data regarding the safety and efficacy of the COVID-19 vaccines are scarce. There are reports of the use of other inactivated vaccines with some biologics proving to be effective and safe. Therefore, considering the potential risk of COVID-19 infection, especially in patients with inborn errors of immunity, we recommend that COVID-19 vaccines should be used in patients using biologics. Thus, there is a need for studies to assess these issues, given that therapy with several biologics has been widely used in patients with allergic and immunological diseases.

Reinfecções pelo SARS-CoV-2: fato ou fake ? Implicações para a resposta vacinal / Reinfection with SARS-CoV-2: fact or fake? Implications for vaccine response

Há evidências atuais de que a reinfecção pelo SARS-CoV-2 é uma realidade, mas na grande maioria das situações não houve investigação que permitisse sua perfeita caracterização, sendo confirmados poucos casos. Em situações de real reinfecção, esta ocorreu, em sua grande maioria, por variantes do vírus, com diversas mutações, usualmente na proteína da espícula viral, em profissionais de saúde altamente expostos, ou em portadores de imunodeficiências, tanto primárias quanto secundárias. Ressaltamos que as vacinas podem ser modificadas com relativa facilidade, mas a capacidade de fabricação e de distribuição pelo mundo será capaz de acompanhar a demanda por vacinação em massa de forma eficiente? Neste manuscrito, a comissão de estudo da COVID-19 da ASBAI analisa criticamente o conhecimento atual sobre a reinfecção pelo SARS-CoV-2.

There is current evidence that reinfection with SARS-CoV-2 is a reality, but there is also a lack of investigation that would allow its perfect characterization, and few cases have been confirmed. Real reinfections occurred mostly with variants of the virus, with several mutations, usually in the viral spike protein, in highly exposed health professionals or in patients with immunodeficiencies, both primary and secondary. We emphasize that vaccines can be modified relatively easily, but will the manufacturing and distribution capacity around the world be able to keep up with the demand for mass vaccination efficiently? The ASBAI COVID-19 study commission critically analyzes in this manuscript the current knowledge about SARS-CoV-2 reinfection.

Vacinação contra COVID-19 em pacientes portadores de angioedema hereditário: recomendações do Grupo de Estudos Brasileiro em Angioedema Hereditário (GEBRAEH) / COVID-19 vaccination in patients with hereditary angioedema: recommendations from the Brazilian Group for the Study on Hereditary Angioedema (GEBRAEH)

No curso da pandemia da COVID-19, o desenvolvimento rápido de vacinas seguras e eficazes é a principal estratégia de saúde pública para conter a propagação da doença. Nesse contexto, esclarecimentos em relação à prioridade e segurança da vacinação contra COVID-19 em pacientes portadores de angioedema hereditário (AEH), assim como de outras doenças, são necessários. Todos os pacientes devem receber a vacina seguindo a estratégia do Ministério da Saúde e manter as medidas de higiene, uso de máscaras e distanciamento social até o controle da pandemia.

During the COVID-19 pandemic, the rapid development of safe and effective vaccines is the main public health strategy to avoid the spread of the disease. In this context, clarifications regarding the priority and safety of vaccination against COVID-19 in patients with hereditary angioedema (HAE), as well as other diseases, are needed. All patients should receive the vaccine according to the Brazilian Ministry of Health strategy and adhere to measures such as maintaining general hygienic measures, wearing masks, and keeping social distance until the pandemic is controlled.

Vacinas contra a COVID-19 e os erros inatos da imunidade (ou imunodeficiências primárias) / COVID-19 vaccines and inborn errors of immunity (or primary immunodeficiencies)

Desde o início da pandemia de COVID-19 iniciou-se a corrida por uma imunização ativa, eficaz e segura. Todas as vacinas desenvolvidas até o momento vêm demostrando boa eficácia na prevenção de casos graves de COVID-19, de hospitalizações e mortes. Muitos pacientes com erros inatos da imunidade (EII) não terão capacidade de desenvolver uma resposta imune semelhante ao indivíduo imunocompetente. Esses pacientes foram incluídos nos grupos prioritários definidos pelo Ministério da Saúde, como pessoas entre 18 a 59 anos com uma ou mais das comorbidades, incluindo as imunodeficiências primárias. Eles podem e devem receber as vacinas em uso contra o SARS-CoV-2, mas nem sempre apresentarão uma resposta imunológica satisfatória e protetora, e, portanto, seus contactantes também devem ser vacinados.

Since the beginning of the COVID-19 pandemic, the race for an active, effective, and safe immunization has started. All vaccines developed to date have shown good efficacy in preventing serious cases of COVID-19, hospitalization, and death. Many patients with inborn errors of immunity will not be able to develop an immune response similar to that of immunocompetent individuals. These patients were included in the priority groups defined by the Brazilian Ministry of Health, as people between 18 and 59 years of age with one or more comorbidities, including primary immunodeficiencies. They can and should receive the vaccines in use against SARS-CoV-2, but they will not always have a satisfactory and protective immune response, and, therefore, those in direct contact with them should also be vaccinated.

Development of SARS-CoV-2 vaccines / Desarrollo de vacunas contra el SARS-CoV-2

Abstract Background: The coronavirus disease 2019 (COVID-19) pandemic has posed significant challenges globally. Continuous transmission of the virus is mostly due to insufficient infection control measures and a lack of vaccines. Therefore, this review aimed to identify and describe possible vaccines for the prevention of COVID-19. Methods: A systematic review of the scientific literature was performed through electronic searches of the main databases to identify published reports or studies on vaccines under development against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Websites from international organizations, institutes of health and research, Google, and references from identified studies were also reviewed. Studies examining the mechanisms of infection, immunopathology, and genomics were excluded. Results: A total of 141 vaccines in development against SARS-CoV-2 were identified. The technologies used include weakened and inactive viruses, viral vectors, nucleic acids, and proteins. So far, 13 vaccines (9.2%) are under clinical evaluation; only the AZD1222 vaccine is under clinical evaluation Phase II-III. Ad5-nCoV and mRNA-1273 vaccines showed to produce neutralizing antibodies and also to be safe. Conclusions: Despite efforts invested in developing SARS-CoV-2 vaccines, more research is still required. The vaccine developers, international health organizations, and the decision-makers of health policies must carry out conjunct cooperation to face the different challenges and guarantee the development of an effective vaccine.

Resumen Introducción: La pandemia de COVID-19 ha planteado grandes retos en todo el mundo. La transmisión continua del virus se debe, en gran parte, a las medidas deficientes para el control de infecciones y a la falta de vacunas. El objetivo de esta revisión fue identificar y describir las posibles vacunas para la prevención de la COVID-19. Métodos: Se realizó una revisión sistemática de la literatura científica mediante búsquedas en las principales bases de datos electrónicas, para identificar informes o estudios publicados sobre las vacunas en proceso de desarrollo contra el SARS-CoV-2. También se revisaron páginas web de organismos internacionales, institutos de salud e investigación, Google y las referencias de los estudios identificados. Se excluyeron los estudios que examinaron los mecanismos de infección, inmunopatológicos y de genómica. Resultados: En total se identificaron 141 vacunas en desarrollo contra el SARS-CoV-2. Las tecnologías utilizadas incluyen virus debilitados e inactivos, vectores virales, ácidos nucleicos y proteínas. Hasta el momento solo 13 vacunas (9.2%) se encuentran en proceso de evaluación clínica y solo la vacuna AZD1222 se encuentra en fase II-III. Las vacunas Ad5-nCoV y mRNA-1273 han mostrado producción de anticuerpos neutralizantes, además de ser seguras. Conclusiones: A pesar de los esfuerzos invertidos para el desarrollo de vacunas contra el SARS-CoV-2, aún se requiere más investigación. Es necesario que los desarrolladores de vacunas, los organismos internacionales de salud y los tomadores de decisiones de políticas sanitarias cooperen para afrontar los diferentes desafíos y garantizar el desarrollo de una vacuna eficaz.

Covid-19 vaccine management (Comirnaty and mrna-1273 Moderna) in a teaching hospital in Italy: a short report on the vaccination campaign

OBJECTIVES@#In this article, we aim to share our experience in the hospital reorganization made to conduct the SARS-CoV-2 vaccination campaign, based on the principles of flexibility and adaptability.@*STUDY DESIGN@#A descriptive study.@*METHODS@#The data concerning the organization of the vaccination campaign were taken from the operative protocol developed by the hospital dedicated task force, composed by experts in hygiene, public health, occupational medicine, pharmacists, nurses, hospital quality, and disaster managers. Data about the numbers of vaccine administered daily were collected by the Innovation and Development Operative Unit database.@*RESULTS@#Vaccinations against COVID-19 started across the EU on the 27th of December 2020. The first phase of the vaccination campaign carried out in our hospital was directed to healthcare workers immunization including medical residents, social care operators, administrative staff and technicians, students of medicine, and health professions trainees. The second phase was enlarged to the coverage of extremely fragile subjects. Thanks to the massive employment of healthcare workers and the establishment of dynamic pathways, it was possible to achieve short turnaround times and a large number of doses administered daily, with peaks of 870 vaccines per day. From the 27th of December up to the 14th of March a total of 26,341 doses of Pfizer have been administered. 13,584 were first doses and 12,757 were second doses. From the 4th to the 14th of March, 296 first doses of Moderna were dispensed. It was necessary to implement adequate spaces and areas adopting anti-contagion safety measures: waiting area for subjects to be vaccinated, working rooms for the dilution of the vaccine and the storage of the material, vaccination rooms, post-vaccination observation areas, room for observation, and treatment of any adverse reactions, with an emergency cart available in each working area.@*CONCLUSIONS@#The teaching hospital of Pisa faced the beginning of the immunization campaign readjusting its spaces, planning an adequate hospital vaccination area and providing an organization plan to ensure the achievement of the targets of the campaign. This represented a challenge due to limited vaccine doses supplied and the multisectoral teams of professionals to coordinate in the shortest time and the safest way possible. The organizational model adopted proved to be adequate and therefore exploited also for the second phase aimed to extremely fragile subjects.

Vacunas para COVID-19: Estado actual y perspectivas para su desarrollo / COVID-19 vaccines: current status and perspectives for its development

Resumen La pandemia por SARS-CoV-2 evidencia la importancia del trabajo conjunto para el desarrollo de vacunas contra el virus, estas incluyen virus completos, subunidades, vacunas atenuadas, vectores virales y ácidos nucleicos, la mayoría de propuestas están basadas en subunidades proteicas. De los más de 115 candidatos reportados hasta abril, 73 se encuentran en estudios preclínicos, a junio la opción más avanzada se ubica en fase II/II, una en fase II, dos en fase I/II y cuatro en fase I. Los candidatos más avanzados son AZD1222 (AstraZeneca) basada en adenovirus recombinante para la proteína S (fase II/III); PiCoVacc (Sinovac Biotech) basada en virus inactivado (fase I/II); mientras que mRNA-1273 (Moderna) basada en ARNm para la proteína S, INO-4800 (Inovio Pharmaceticals) basada en DNA plasmídico para proteína S, Ad5-nCoV (Cansino Biologicals) basada en adenovirus tipo 5 expresando la proteína S, LV-SMENP-DC basada en células dendríticas con lentivirus para dominios de proteínas virales y aAPC patógeno-específica, basada en células presentadoras de antígenos con lentivirus para dominios de proteínas virales (ambas de Shenzhen Geno-Immune Medical Institute, se encuentran en fase I). La finalidad de este trabajo contrarreloj se dirige hacia el único objetivo de lograr un candidato a vacuna que demuestre seguridad y efectividad en el control y prevención del virus sorpresivo que dejó al descubierto que no hay enemigo pequeño o que mientras más pequeño más peligroso, pues el causante de COVID-19 no solo atacó la salud humana sino la economía del planeta y las costumbres y actividades rutinarias que desarrollaba la humanidad.

ABSTRACT The SARS-CoV-2 pandemic shows the importance of joint work for the development of vaccines against the virus, these include complete viruses, subunits, attenuated vaccines, viral vectors and nucleic acids, most of the proposals are based on protein subunits. Of the more than 115 candidates reported until April, 73 are in preclinical studies, as of June the most advanced option is in phase II / II, one in phase II, two in phase I / II and four in phase I. The candidates more advanced are AZD1222 (AstraZeneca) based on recombinant adenovirus for protein S (phase II / III); PiCoVacc (Sinovac Biotech) based on inactivated virus (Phase I / II); while mRNA-1273 (Modern) based on mRNA for protein S, INO-4800 (Inovio Pharmaceticals) based on plasmid DNA for protein S, Ad5-nCoV (Cansino Biologicals) based on adenovirus type 5 expressing protein S, LV- SMENP-DC is based on dendritic cells with lentiviruses for viral protein domains and pathogen-specified aAPC, based on antigen-presenting cells with lentiviruses for viral protein domains (Shenzhen Institute of Genoimmune Medicine, are in phase I). The purpose of this work against the clock is directed towards the sole objective of achieving a vaccine candidate who demonstrates safety and determination in the control and prevention of the surprising virus that revealed that there is no small enemy or that the smaller the more dangerous, because the cause of COVID-19 not only attacked human health but the economy of the planet and the customs and routine activities that humanity develops.

SARS-CoV-2: previous coronaviruses, immune response, and development of vaccines / SARS-CoV-2: coronavirus previos, respuesta inmune y desarrollo de vacunas

Abstract Since the emergence of the new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China at the end of 2019, when its characteristics were practically unknown, one aspect was evident: its high contagion rate. This high infection rate resulted in the spread of the virus in China, Europe, and, eventually, the rest of the world, including Mexico. At present, around 9 million people are infected, and around 470,000 have died worldwide. In this context, the need to generate protective immunity, and especially the generation of a vaccine that can protect the world population against infection in the shortest possible time, is a challenge that is being addressed in different countries using different strategies in multiple clinical trials. This opinion article will present the evidence of the induction of immune response in some of the viruses of the coronavirus family before COVID-19, such as SARS-CoV and MERS-CoV (Middle East respiratory syndrome coronavirus). The information collected about the induction of an immune response by SARS-CoV-2 will be presented, as well as a description of the vaccine candidates reported to date in the various ongoing clinical trials. Finally, an opinion based on the evidence presented will be issued on the potential success of developing vaccine prototypes.

Resumen Desde el surgimiento del nuevo coronavirus SARS-CoV-2 (coronavirus tipo 2 del síndrome respiratorio agudo severo) en China a finales del año 2019, cuando todavía era desconocido prácticamente en todos los aspectos, una característica era evidente: el alto índice de contagio entre la población. Esto resultó en la expansión del virus en China, Europa y, finalmente, en el resto del mundo, incluyendo México. Actualmente, alrededor de 9 millones de personas están infectadas, y han muerto cerca de 500,000 en todo el mundo. En este contexto, la necesidad de generar inmunidad protectora y, sobre todo, el desarrollo de una vacuna que pueda proteger a la población mundial contra la infección en el menor tiempo posible, es un reto que se está abordando en distintos países utilizando diversas estrategias en múltiples ensayos clínicos. En este artículo de opinión se presentan las evidencias de la inducción de respuesta inmunitaria con algunos de los virus de la familia de coronavirus previos al SARS-CoV-2, como el SARS-CoV (coronavirus del síndrome respiratorio agudo severo) y el MERS-CoV (síndrome respiratorio por coronavirus de Oriente Medio). Además, se presenta lo reportado hasta el momento acerca de la inducción de respuesta inmunitaria por el SARS-CoV-2, así como una descripción de los candidatos a vacunas informados hasta el momento en los distintos ensayos clínicos en curso. Finalmente se emite una opinión, basada en las evidencias presentadas, acerca del éxito potencial de los prototipos de vacunas en desarrollo.