Background The Sinovac enterovirus 71 (EV71) vaccine has been given to children aged 6–35 months with good safety, immunogenicity, and efficacy. Further exploration is needed for the application of Sinovac EV71 vaccine in older children. Methods A phase III, double-blind, single-center, randomized, controlled, non-inferiority, and bridging-designed trial enrolled 300 participants aged 6–35 months and 600 participants aged 36–71 months. Non-inferiority and superiority analyses were made to determine the immunogenicity of Sinovac EV71 vaccine in older children (Older-S group), comparing with that of control EV71 vaccine in the same age group (Older-C group), or comparing with that of Sinovac EV71 vaccine in younger children (Younger-S group). Results The seroconversion rate of anti-EV71 in Older-S group (95.5%) was superior to that of Older-C group (86.0%), and non-inferior to that of Younger-S group (98.5%). For baseline seronegative participants, the geometric mean titer of Older-S group (370.0) was non-inferior to that of Older-C group (296.2) and superior to that of Younger-S group (176.5). Incidence of adverse reactions in Older-S group (47.0%) was similar to that of Older-C group (44.8%), or Younger-S group (49.8%). Conclusions This study showed good safety and immunogenicity of Sinovac EV71 vaccine in children aged 36–71 months. Clinical Trials Registration NCT03909074 URL https://clinicaltrials.gov/ct2/show/NCT03909074?term=NCT03909074&draw=2&rank=1

Background: The Sabin-strain-based inactivated poliovirus vaccine (sIPV) plays an important role in poliomyelitis eradication in developing countries. As part of the phase III clinical development program, this study aimed to evaluate the safety, immunogenicity and lot-to-lot consistency of the sIPV in 2-month-old infants. Method: We conducted a phase III, randomized, double-blind, positive-controlled trial in which 1300 healthy infants were randomly assigned to four groups in a 1:1:1:1 ratio to receive one of the three lots of the sIPV or the control IPV at 2, 3 and 4 months of age. Serum samples were collected before the first dose and 30 days after the third dose of vaccination to assess the immunogenicity. Solicited local and systemic reactions were recorded within 7 days and unsolicited adverse events within 30 days after each vaccination. Results: Of the 1300 randomized infants, 1190 infants completed the study and were included in the per-protocol population. The seroconversion rates in the three lots of the sIPV were 95.67%, 97.03% and 95.59%, respectively, for type 1; 94.33%, 93.73% and 92.88%, respectively, for type 2; and 98.67%, 99.67% and 99.32%, respectively, for type 3. The ratios of GMTs for poliovirus types 1, 2 and 3 of each pair of lots were all between 0.67 and 1.50, therefore meeting the predefined immunological equivalence criteria. For the seroconversion rate of poliovirus types 1, 2 and 3, the pooled sIPV group was non-inferior to the IPV group. The incidence of solicited and unsolicited adverse reactions (ARs) was similar in the pooled sIPV lots and the IPV group, and most of them were mild to moderate in severity. Non-vaccine-related serious adverse events (SAEs) were reported. Conclusions: Three consecutive lots of sIPV demonstrated robust and consistent immunogenicity. The safety and tolerability of the sIPV was acceptable and similar to that of the IPV.

What is already known about this topic? Neutralization levels induced by inactivated vaccines rapidly wane after primary immunization, and a homologous booster can recall specific immune memory, resulting in a remarkable increase in antibody concentration. The optimal interval between primary and booster doses has yet to be determined. What is added by this report? Booster doses given at three months or more after the two-dose regimen of the CoronaVac COVID-19 vaccine in elderly individuals aged 60 years and older triggered good immune responses. The geometric mean titers of neutralizing antibody on Day 14 after the booster doses increased by 13.3–26.2 fold of baseline levels, reaching 105.45–193.59 in groups with different intervals (e.g., 3, 4, 5, and 6 months). What are the implications for public health practice? A 4- to 5-month interval between receiving the primary and booster series of CoronaVac could be an alternative to the 6-month interval in order to promote vaccine-induced immunity in elderly individuals. The findings support the optimization of booster immunization strategies.

Following the emergence of COVID-19, breakthrough SARS-CoV-2 infections have demonstrated substantial heterogeneity in both occurrence and clinical severity. This case–control study aimed to elucidate the factors associated with the incidence, duration, and severity of SARS-CoV-2 symptoms among Chinese adults during the Omicron wave. The analysis was based on data from a national COVID-19 surveillance program encompassing six provinces—Jiangsu, Chongqing, Shandong, Hunan, Anhui, and Yunnan—and included both laboratory-confirmed and clinically diagnosed cases. Data were systematically collected between February and April 2023. For each confirmed case, a matched control was selected through simple random sampling, matched on sex, age (±5 years), and province of residence. Multivariate logistic regression analyses were employed to assess a range of potential determinants, including demographic characteristics, lifestyle behaviors, and pre-existing medical conditions, in relation to the risk of infection, as well as the persistence and severity of symptoms following SARS-CoV-2 breakthrough infection. A total of 10,426 cases and 10,426 matched controls were included in the final analysis. Among the infected individuals, 963 (9.24%) reported persistent symptoms, while 773 (7.41%) experienced moderate-to-severe clinical manifestations. Occasional alcohol consumption, presence of comorbidities, tea and coffee intake, overweight status, and a longer interval since the last vaccination dose were all significantly associated with increased odds of infection (OR > 1, FDR < 0.05). Conversely, weekly alcohol consumption and smoking were associated with a decreased risk (OR < 1, FDR < 0.05). Female sex was significantly associated with both persistent and moderate-to-severe symptoms. Additional risk factors for prolonged or severe symptoms included older age, being underweight or overweight, a history of immunotherapy, coffee consumption, and the presence of comorbidities. These findings underscore the multifactorial nature of SARS-CoV-2 infection outcomes and highlight the interplay between host characteristics and behavioral factors. The results support the development of personalized prevention strategies aimed at reducing the clinical burden and long-term impact of COVID-19.

Since the introduction of Pasteur's rabies vaccine in 1885, rabies prophylaxis and post-exposure prophylaxis (PEP) have been widely administered globally under the recommendation of the World Health Organization (WHO). However, 124 documented cases of PEP failure had been reported worldwide between 1980 and 2023. Additionally, sporadic media reports from China had highlighted occasional PEP failures between 2017 and 2024. These incidents underscore the ongoing global challenge of ensuring the effectiveness of PEP. Rabies remains a serious public health problem in over 150 countries and regions. In this review, we summarize widely recognized PEP procedures recommended by the Advisory Committee on Immunization Practices (ACIP) and the WHO. We also analyze potential contributing factors to PEP failure, propose a concept of circulating antibodies, and discuss their roles in PEP. Furthermore, we summarize key guidelines for clinical trial design from U.S. Food and Drug Administration (FDA) and China’s Center for Drug Evaluation (CDE), and share the latest developments in monoclonal antibody (cocktail) therapies. Adherence to core PEP practices, such as wound cleansing, infiltration of wounds with immunoglobulin (mAbs), and administration of vaccines, is crucial for preventing rabies infection in most cases. For high-risk exposures or immunocompromised individuals, the provision of circulating antibodies through high-dose human rabies immune globulin (HRIG) or mAbs is of utmost importance to prevent PEP failure. Addressing rabies requires the involvement of the entire society. Only through collective efforts can we tackle this neglected disease and achieve the WHO’s goal of “zero by 30”.

Background: Since the introduction of Pasteur’s rabies vaccine in 1885, rabies prophylaxis and post-exposure prophylaxis (PEP) have been widely administered globally under the recommendation of the World Health Organization (WHO). However, 124 documented cases of PEP failure had been reported worldwide between 1980 and 2023. Additionally, sporadic media reports from China showed occasional PEP failures between 2017 and 2024. Rabies remains a serious public health problem in over 150 countries and regions. Methods: In this review, we summarize PEP procedures recommended by the Advisory Committee on Immunization Practices (ACIP) and the WHO. We also analyze potential contributing factors to PEP failure, propose a concept of circulating antibodies, and discuss their roles in PEP. Furthermore, we summarize key guidelines for clinical trial design from the U.S. Food and Drug Administration (FDA) and China’s Center for Drug Evaluation (CDE), as well as the latest developments in monoclonal antibody (cocktail) therapies. Results: Adherence to core PEP practices, such as wound cleansing, infiltration of wounds with immunoglobulin (mAbs), and administration of vaccines, and broader societal involvement are crucial for preventing rabies infection in most cases. For high-risk exposures or immunocompromised individuals, the provision of circulating antibodies through high-dose human rabies immune globulin (HRIG) or mAbs is of utmost importance for preventing PEP failure. Conclusions: Early, high-concentration circulating antibodies are important for preventing PEP failure. Addressing the global issue of rabies requires involvement of the entire society. Only through collective efforts can we tackle this neglected disease and achieve WHO’s goal of “zero by 30”.