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

Scholars say 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 research and development landscape of new crown vaccines As of September 2, 2020, the global new crown vaccine development pipeline includes 321 candidate vaccines, an increase of more than 2.5 times over 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 data supporting approval are expected later this year.
the fastest-growing candidate vaccines have already started mass production so that they can be distributed quickly when approved.
technology platforms and antigen types Current new crown candidate vaccine pipelines include a wide range of technology platforms, ranging from proven traditional methods to innovative methods that have not yet been approved for any vaccine.
, although vaccines based on several different platforms in use have reported encouraging antibody and T-cell immune responses, it is too early to assess their relative potential.
11 clinical phase candidate vaccines were used to strengthen the body's immune response.
of new crown candidate vaccine pipelines, a: exploratory and preclinical pipelines;
Traditional methods include detoxification and inactivated vaccines, and innovative methods include viral vectors, RNA, DNA, recombinant proteins, peptides, virus-like particles (Photo Source: Resources) Most candidate vaccine candidates currently in clinical trials use the neocovirus pyrethroid (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 biggest change in the new crown vaccine development institutions is the increasing participation of large multinational companies.
Eight of its current clinical candidates have been funded by the Alliance for Epidemiological Prevention and Innovation (CEPI) and are now included in COVAX's portfolio, a collaboration led by CEPI, Gavi and WHO to provide 2 billion doses of vaccines for global distribution by 2021.
New Crown Vaccine Development Agency Profile, "Other Industries" category includes companies other than "Transnational Pharmaceutical Companies" (Photo Source: Reference: References) The progress of new crown vaccines entering the clinical phase of clinical development has been developed to provide insight into future new crown vaccine development efforts, which 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 Design In conventional clinical trials, in order to calculate the number of participants, researchers preferred to accurately estimate the occurrence of primary clinical endpoint background in placebo group participants (e.g., new coronavirus infection rates in unvaccinated cases, the rate of symptomatic COVID-19, etc.).
, however, rapid changes in the neo-crown outbreak 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 in which 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.
the choice of clinical endpoints is critical to selecting a relevant 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 that 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 vaccine impact on endpoints, and the reliability of measuring end points.
, for example, Moderna's ongoing Phase 3 clinical trials use patients with COVID-19 who test positive for nucleic acid and have symptoms as the primary clinical endpoint and have strictly defined symptoms (see figure below).
Photo Source: Moderna.com 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 that are not included in the main endpoints of clinical trials should be evaluated as secondary endpoints.
between the virus and the ability to protect those infected with the new coronavirus, what protective immunity is has not yet been determined.
, however, the latest data suggest that both the antibody and cell-mediated immune responses are important in the immune response of the new coronavirus, and that potential vaccines should induce both responses.
target populations to relax the selection criteria for clinical trials to broaden the trial population is essential for later trials of the new crown vaccine.
study should represent the wider population that will use the vaccine and should make every effort to demonstrate vaccine effectiveness 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.
safety considerations The development of adequate safety databases is 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 Although the new crown candidate vaccine is progressing at an extraordinary rate to the late stages of clinical development, many uncertainties remain in view of the lack of strong clinical data to date.
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 across the 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.
resources: (1) Le et al., (2020). Evolution of the COVID-19 vaccine development landscape. Nature Reviews Drug Discovery, doi: 10.1038/d41573-020-00151-8 s2 mRNA-1273 Clinical Development Program. Retrieved September 6, 2020, from.