Nature sub-journal review: What needs attention to be paid to the late clinical development of the new crown vaccine?

Since the outbreak of the new crown outbreak, the development of a safe and effective new crown vaccine is one of the first strategies to control the outbreak.
with the efforts of global biomedical and biotechnology researchers, the development of new crown candidate vaccines can be considered "rapidly changing".
almost every day, candidate vaccine development projects are born, or new advances are announced before or during the clinical period.
, researchers from the Alliance for Innovation in Epidemiology Prevention (CEPI) released an inventory of the new crown vaccine development pipeline at the Nature Reviews Drug Discovery.
CEPI funded the early development of several candidate new crown vaccines in the early stages of the outbreak, many of which are already in clinical development.
is also an important member of the World Health Organization's (WHO) Vaccines Section of the Access to COVID-19 Tool Acceleration Program.
said today's new crown vaccine development pipeline has changed considerably compared with a preliminary analysis of vaccine pipelines conducted in April.
in this updated review, they will focus on candidate vaccines in the clinical development phase and provide some preliminary insights into their clinical development.
evolution of the new crown vaccine development landscape as of September 2, 2020, the global new crown vaccine research and development pipeline includes 321 candidate vaccines, an increase of more than 2.5 times compared to the April report.
, 32 vaccine candidates are in clinical trials and plan to recruit more than 280,000 subjects from at least 470 research centers in 34 different countries.
fastest-growing clinical candidate vaccine is currently in phase 3 clinical trials, and supporting the approval is expected later this year.
the fastest-growing candidate vaccines have already started mass production so that they can be distributed quickly when approved.
current new crown candidate vaccine pipelines for the technology platform and antigen type include a wide range of technology platforms, ranging from proven traditional methods to innovative methods that have not yet been approved for vaccines.
although encouraging antibodies and T-cell immune responses have been reported based on vaccines being used on several different platforms, it is too early to assess their relative potential.
adrenasts to strengthen the body's immune response in 11 clinical phases.
new crown candidate vaccine pipeline, a: exploratory and preclinical pipeline; b: clinical period pipeline.
Traditional methods include detoxification and inactivated vaccines; innovative methods include viral vectors, RNA, DNA, recombinant proteins, peptides, virus-like particles (Photo Source: Reference 1) Most candidates for vaccines currently in clinical trials use the new coronavirus protrusion (S) protein and its variants as major antigens.
, however, development projects are under way for candidate vaccines based on a variety of other antigens, including candidate vaccines targeting the N protein, detoxification vaccines, inactivated vaccines and peptide vaccines.
in the study of the new crown vaccine antigen type classification (photo source: reference: reference) vaccine research and development institutions since April, the overall new crown vaccine development institutions, the biggest change is the increasing participation of large multinational companies.
Eight of its current clinical candidates have been funded by the Alliance for Innovation in Epidemiology Prevention (CEPI) and are now included in COVAX's portfolio, a partnership led by CEPI, Gavi and WHO to provide 2 billion doses of vaccines for global distribution by 2021.
An overview of the New Crown Vaccine Development Agency, the "other industryy" category includes companies other than "transnational pharmaceutical companies" (Photo Source: Reference: Resources) the progress of the new crown vaccine for clinical development, which has been developed to provide insight into future new crown vaccine development efforts, and these experiences will also help to design vaccine development strategies to respond to future outbreaks of infectious diseases.
WHO has released a target product profile for the new crown vaccine and provided guidance for the design, implementation, evaluation and follow-up of clinical trials.
of the most important considerations for clinical development of new crown candidate vaccines are summarized below.
Clinical trials are designed in conventional clinical trials, and in order to calculate the number of participants, the researchers preferred to accurately estimate the occurrence of the primary clinical endpoint background of the placebo group participants (e.g., the rate of new coronavirus infection in unvaccinated cases, the rate of symptomatic COVID-19, etc.).
, however, the rapid changes in neo-crown outbreaks mean that predicting morbidity is challenging, and public health interventions such as social distance to control the spread of the virus may further complicate the predicted incidence.
refore, researchers should consider adaptive case-driven trial designs where the degree of certainty and accuracy of clinical trials is determined not by the size of the trial, but by the total number of COVID-19 cases at the main endpoint.
recruitment can be stopped when the minimum number of events is reached, resulting in more efficient and rapid clinical trials.
choose a clinical endpoint that reflects the expected public health benefits.
endpoints considered in clinical trials of the new crown vaccine include clinical diseases of varying severity and/or asymptomatic infections.
history, respiratory and other mucosal virus vaccines have been more effective against more serious diseases than milder ones and are less likely to affect asymptomatic infections.
addition, the use of asymptomatic new coronavirus infections as an endpoint can be operationally challenging and lead to a large number of false positive test results and may not even prove vaccine effectiveness.
, the use of clinical endpoints that require symptoms of pneumonia may lead to earlier proof of vaccine effectiveness.
therefore, when setting clinical endpoints, consideration should be given to the likely occurrence of major endpoints in the study population, the importance of vaccines in terms of endpoint impact, and the reliability of measuring endpoints.
, for example, Moderna's ongoing Phase 3 clinical trials use patients with COVID-19 who have tested positive for nucleic acid and are symptomatic as the primary clinical endpoint and have strictly defined symptoms (see figure below).
Photo Source: In the case of a pandemic caused by a new pathogen, it is important to maintain some flexibility in the definition of clinical endpoint due to limited knowledge of pathogen-specific disease manifestations and underlying pathophysiology.
this flexibility to collect clinical case data in early clinical trials, improve case definitions based on the knowledge gained in later trials, and determine vaccine efficacy with new pathological standards.
, however, viral infections or other disease endpoints not included in the main endpoints of clinical trials should be evaluated as secondary endpoints.
and protection capabilities, what protective immunity is for those infected with the new coronavirus has not yet been determined.
, however, the latest data suggest that both the antibody and cell-mediated immune responses are important in the immune responses of the new coronavirus, and that potential vaccines should induce both responses.
the target population to relax the selection criteria for clinical trials to broaden the trial population is essential for later trials of the new crown vaccine.
the study should represent a wider population that will use the vaccine and make every effort to demonstrate the effectiveness of the vaccine as early as possible in terms of participant recruitment strategies.
Therefore, participation in clinical trials should be encouraged to adequately represent populations at risk of new coronavirus infections and/or serious consequences, such as front-line health care workers, the elderly and people with potential health conditions, who may benefit most from safe and effective vaccines.
security considerations are critical to the regulatory approval and public acceptance of any new vaccine, especially those using new technology platforms.
to coordinate the safety data collection of candidate vaccines to maximize their comparability and value.
In this regard, the following tools are available to researchers, including a variety of tools recommended by the WHO: Standardized Case Definitions (AEFI) for 60 Post-Immunized Adverse Events;
the future, many uncertainties remain, given the lack of strong clinical data to date, despite the extraordinary pace at which new crown candidates are progressing to the late stages of clinical development.
the fastest-growing vaccine candidates will begin reporting critical clinical trial data in the coming months and, if the data are positive, will be used to support accelerated approval of the first new crown candidates.
data will also provide valuable insights into the entire field and provide information for future research and development activities.
research and development activities are aimed not only at controlling the current global pandemic, but also at providing effective long-term immunization strategies against the disease.
References: Le et al., (2020). Evolution of the COVID-19 vaccine development landscape. Nature Reviews Drug Discovery, doi: 10.1038/d41573-020-00151-8 . Retrieved September 6, 2020, from . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .