Maternal immunization is a highly effective public health strategy. The administration of vaccines to pregnant women increases the level of specific transplacental maternal antibodies, thereby protecting the pregnant fetuses, newborns, and early-life infants from the corresponding pathogens. Currently, maternal immunization strategies for pertussis, influenza, etc. have been widely used worldwide, and positive results have been achieved in preventing respiratory syncytial virus infection in infants. This article reviews different designs of maternal vaccination clinical studies, including randomized controlled trials, cohort studies, case-control studies, and surveillance data studies. It summarizes the strengths and weaknesses of different study approaches and discusses the application of maternal immunization strategies to provide a reference for developing maternal immunization research in China.

The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

Multi-conjugate vaccine and polyvalent vaccine can reduce the number of vaccinations, improve vaccination efficiency, and provide wider protection against diseases, and can not only brings convenience to recipients but also reduce healthcare costs, making it a key focus in modern vaccine development. However, even if the components of the vaccine are derived from already approved monovalent vaccines, it must still be considered as a new vaccine and undergo randomized controlled clinical trials to evaluate their safety and efficacy in humans. Due to the inclusion of multiple antigens, clinical evaluation must consider the potential interactions between or among the components, as well as the impacts of adjuvants, preservatives, and other ingredients on the vaccines' safety and efficacy. These factors introduce certain specific challenges in the clinical evaluation of multi-conjugate vaccine and polyvalent vaccine. This article summarizes the key elements and methods of clinical study design for multi-conjugate vaccine and polyvalent vaccine in terms of safety, immunogenicity, and protective efficacy, and discuss the problems and challenges exisitng in vaccine clinical evaluation to provide reference for the standardization of clinical study design of multi-conjugate vaccine and polyvalent vaccine.

The impact of vaccines on public health and their effectiveness in controlling infectious diseases partly depends on their coverage rate, which refers to the proportion of individuals vaccinated within a specific population. Vaccination coverage is foundational data for vaccine immunization programs, a key parameter for evaluating and monitoring the implementation of vaccination plans, and an important data point in real-world post-market studies of vaccines. Additionally, research on vaccination coverage is becoming increasingly prevalent in vaccine evaluation, primarily used to establish the risk of disease incidence in populations with different vaccination coverage rates in order to assess the protective effectiveness of vaccines. This paper reviews the research methods used to assess vaccine coverage both domestically and internationally, as well as their applications in evaluating vaccine effectiveness. It also analyzes and compares the advantages and disadvantages of different research methods for measuring vaccination coverage and discusses the significance of monitoring and improving vaccine coverage rates. The goal is to promote research and application of vaccination coverage rates in China, providing a scientific basis for post-market vaccine studies and for local administrative departments to formulate immunization policies.

Maternal immunization is a highly effective public health strategy. The administration of vaccines to pregnant women increases the level of specific transplacental maternal antibodies, thereby protecting the pregnant fetuses, newborns, and early-life infants from the corresponding pathogens. Currently, maternal immunization strategies for pertussis, influenza, etc. have been widely used worldwide, and positive results have been achieved in preventing respiratory syncytial virus infection in infants. This article reviews different designs of maternal vaccination clinical studies, including randomized controlled trials, cohort studies, case-control studies, and surveillance data studies. It summarizes the strengths and weaknesses of different study approaches and discusses the application of maternal immunization strategies to provide a reference for developing maternal immunization research in China.

The master protocol design encompasses a comprehensive clinical trial protocol containing multiple sub-protocols, which can be used to evaluate the clinical intervention effects of various drugs or vaccines on various diseases. Particularly, this design strategy represents an efficient and innovative approach to trial design in the context of precision medicine. The master protocol design can be used for emerging infectious diseases and urgent vaccine development in complex situations. This review aims to outline the types and concepts of master protocol design, analyze the key points and details, and discuss its application scenarios in vaccine clinical evaluations. Additionally, it will explore potential challenges that may arise during implementation to provide references for optimizing emergency clinical trial designs of infectious disease vaccines in China.

Multi-conjugate vaccine and polyvalent vaccine can reduce the number of vaccinations, improve vaccination efficiency, and provide wider protection against diseases, and can not only brings convenience to recipients but also reduce healthcare costs, making it a key focus in modern vaccine development. However, even if the components of the vaccine are derived from already approved monovalent vaccines, it must still be considered as a new vaccine and undergo randomized controlled clinical trials to evaluate their safety and efficacy in humans. Due to the inclusion of multiple antigens, clinical evaluation must consider the potential interactions between or among the components, as well as the impacts of adjuvants, preservatives, and other ingredients on the vaccines' safety and efficacy. These factors introduce certain specific challenges in the clinical evaluation of multi-conjugate vaccine and polyvalent vaccine. This article summarizes the key elements and methods of clinical study design for multi-conjugate vaccine and polyvalent vaccine in terms of safety, immunogenicity, and protective efficacy, and discuss the problems and challenges exisitng in vaccine clinical evaluation to provide reference for the standardization of clinical study design of multi-conjugate vaccine and polyvalent vaccine.

The impact of vaccines on public health and their effectiveness in controlling infectious diseases partly depends on their coverage rate, which refers to the proportion of individuals vaccinated within a specific population. Vaccination coverage is foundational data for vaccine immunization programs, a key parameter for evaluating and monitoring the implementation of vaccination plans, and an important data point in real-world post-market studies of vaccines. Additionally, research on vaccination coverage is becoming increasingly prevalent in vaccine evaluation, primarily used to establish the risk of disease incidence in populations with different vaccination coverage rates in order to assess the protective effectiveness of vaccines. This paper reviews the research methods used to assess vaccine coverage both domestically and internationally, as well as their applications in evaluating vaccine effectiveness. It also analyzes and compares the advantages and disadvantages of different research methods for measuring vaccination coverage and discusses the significance of monitoring and improving vaccine coverage rates. The goal is to promote research and application of vaccination coverage rates in China, providing a scientific basis for post-market vaccine studies and for local administrative departments to formulate immunization policies.

The seamless phase Ⅱ/Ⅲ design integrates independent phase Ⅱ and phase Ⅲ clinical trials into a continuous, phased adaptive clinical trial design. Compared with traditional independent phase Ⅱ and phase Ⅲ clinical trials, the seamless design offers significant advantages in accelerating drug or vaccine development and improving clinical trial efficiency. Currently, the application of this design in anti-tumor drug research is becoming increasingly mature, and it is gradually expanding to clinical trials of vaccines, including the 9-valent human papillomavirus vaccine, sabin strain inactivated polio vaccine, and others. This paper aims to clarify the seamless phase Ⅱ/Ⅲ design concept and offer valuable insights into its implementation. It accomplishes this by presenting a clinical trial example featuring a phase Ⅱ/Ⅲ seamless design for a 9-valent human papillomavirus vaccine. The article delves into the specific considerations and potential challenges related to implementing the seamless design, aiming to provide valuable insights for optimizing vaccine clinical trials within our country.

Objective:To analyze the effects of SARS-CoV-2 infection and vaccination on virus mutation.Methods:The whole genome sequencing sequences of 2 659 local SARS-CoV-2 specimens from Jiangsu Province in 2023 were selected for analysis, and relevant information such as demographic and clinical characteristics were collected, and the effects of infection and vaccination on the genome-wide mutation rate and S gene′s selective pressure of the virus were analyzed by univariate and multivariate linear regression models.Results:The average age of these infected patients was 55.0 (31.0, 74.0) years, 1 150 cases (43.2%) in the age group of ≥60 years, 1 367 cases (51.4%) were males, 2 044 cases (76.9%) had a history of COVID-19 vaccination, and 1 629 cases (61.3%) had the first-time infection. The clinical symptoms of the infected patients were mainly mild, with a total of 2434 cases (91.5%), and 29 cases (1.1%) with severe symptoms or more. The average substitution rate of SARS-CoV-2 was 9.69 (9.38, 9.98)×10 -4 subs/site/year, and the dN/dS value of the S gene was 6.08 (5.56, 8.66), which was significantly greater than that of 1 ( P<0.001), indicating positive selection. The result of univariate and multivariate linear regression model analysis showed that the SARS-CoV-2 substitution rate was higher in those with vaccination history and reinfection, aged 20-30 years, ≥60 years, and the SARS-CoV-2 substitution rate was lower in males with moderate clinical symptoms and severe disease and above. Those with a history of vaccination and reinfection, aged 50-60 years old, ≥60 years old have smaller S gene dN/dS. Conclusions:Under the immune pressure exerted by vaccination and infection, the genome-wide mutation of SARS-COV-2 accelerated, but the non-synonymous mutation rate of the S gene decreased. The mechanism causing these phenomena needs further study.