Study on immune persistence of the CTN-1V strain rabies vaccine in humans.

This study is a single-arm, single-center phase IV clinical trial on a rabies vaccine that has been marketed in China. The Vero cells and CTN-1V strain are used in the rabies vaccine product. The purpose of this study was to investigate the safety, immunogenicity and immune persistence of this product. One hundred and forty-nine participants were enrolled to the study, all of whom were included in the safety analysis set (SS), among which 116 participants were included in the protocol analysis set (PPS), One hundred and fifteen participants were included in the 6-month immune persistence analysis set (IPS6) and 111 in the 12-month immune persistence analysis set IPS12. Results showed that: 1) In the SS analysis set, adverse reactions were mainly pyrexia and pain at the vaccination site, the severity of which were mostly grade 1, and concentrated in 0-3 days after vaccination. No grade 3 or above adverse events and serious adverse events (SAE) related to the experimental vaccine were observed. 2) In the PPS analysis set, the antibody positive conversion rate reached 100% at 14 days after full immunization of the pre-immunized negative population; The antibody geometric mean titer (GMT) (95% CI) was 14.82 (13.00, 16.90). 3) The positive rate of serum neutralizing antibody was 93.91 % and the GMT at 1.58 IU/ml at 6 months after full immunization. The positive rate of neutralizing antibody was 85.59 % and GMT at 1.30 IU/ml at 12 months after immunization. Our results show that the human rabies vaccine with the CTN-1V strain and Vero cells as matrix had good safety, immunogenicity and immune persistence in our study.

Immune-Boosting Effect of the COVID-19 Vaccine: Real-World Bidirectional Cohort Study.

BACKGROUND: As the SARS-CoV-2 attenuates and antibodies from the COVID-19 vaccine decline, long-term attention should be paid to the durability of primary booster administration and the preventive effect of the second or multiple booster doses of the COVID-19 vaccine. OBJECTIVE: This study aimed to explore the durability of primary booster administration and the preventive effect of second or multiple booster doses of the COVID-19 vaccine. METHODS: We established a bidirectional cohort in Guizhou Province, China. Eligible participants who had received the primary booster dose were enrolled for blood sample collection and administration of the second booster dose. A retrospective cohort for the time of administration was constructed to evaluate antibody attenuation 6-12 months after the primary booster dose, while a prospective cohort on the vaccine effect of the second booster dose was constructed for 4 months after the second administration. RESULTS: Between September 21, 2022, and January 30, 2023, a total of 327 participants were included in the final statistical analysis plan. The retrospective cohort revealed that approximately 6-12 months after receiving the primary booster, immunoglobulin G (IgG) slowly declined with time, while immunoglobulin A (IgA) remained almost constant. The prospective cohort showed that 28 days after receiving the second booster, the antibody levels were significantly improved. Higher levels of IgG and IgA were associated with better protection against COVID-19 infection for vaccine recipients. Regarding the protection of antibody levels against post-COVID-19 symptoms, the increase of the IgG had a protective effect on brain fog and sleep quality, while IgA had a protective effect on shortness of breath, brain fog, impaired coordination, and physical pain. CONCLUSIONS: The IgG and IgA produced by the second booster dose of COVID-19 vaccines can protect against SARS-CoV-2 infection and may alleviate some post-COVID-19 symptoms. Further data and studies on secondary booster administration are required to confirm these conclusions.

Immunogenicity and safety of an inactivated enterovirus 71 vaccine coadministered with trivalent split-virion inactivated influenza vaccine: A phase 4, multicenter, randomized, controlled trial in China.

Background: Few data exist on the immunogenicity and safety of an inactivated enterovirus 71 vaccine (EV71 vaccine) coadministered with trivalent split-virion inactivated influenza vaccine (IIV3) in infants. Methods: This trial was a phase 4, randomized, controlled trial. Infants aged 6-11 months were eligible, with no history of hand, foot and mouth disease (HFMD) and no history of EV71 vaccine or any influenza vaccine. Eligible infants were randomly assigned to EV71+IIV3 group, EV71 group or IIV3 group. Blood samples were collected on day 0 and 56. Results: Between September 2019 and June 2020, 1151 infants met eligibility criteria and 1134 infants were enrolled. 1045 infants were included in the per-protocol population, including 347 in the EV71+IIV3 group, 343 in the EV71 group, and 355 in the IIV3 group. The seroconversion rate (98.56% vs 98.54%; seroconversion rates difference of 0.02% [95% CI: 0.70-0.98]) and GMT (419.05 vs 503.72; GMT ratio of 0.83 [95% CI 0.70 - 0.98]) of EV71 neutralizing antibodies in the EV71+IIV3 group was not inferior to those in the EV71 group. The non-inferiority results for influenza virus antibodies (A/H1N1, A/H3N2 and B) showed that the seroconversion rates and GMTs of the EV71+IIV3 group were non-inferiority to those of the IIV3 group. Systemic and local adverse event rates were similar between groups. None of serious adverse events (SAEs) were related to vaccination. Conclusions: Coadministration of the EV71 vaccine with IIV3 was safe and did not interfere with immunogenicity. These findings support a viable immunization strategy for infants with the EV71 vaccine coadministered with IIV3 in China. This trial is registered with ClinicalTrials.gov, number NCT04091880.

Evaluation of Immunogenicity and Safety of Vero Cell-Derived Inactivated COVID-19 Vaccine in Older Patients with Hypertension and Diabetes Mellitus.

BACKGROUND: To evaluate the immunogenicity and safety of the COVID-19 vaccine (Vero cell), inactivated, in a population aged ≥60 years with hypertension or(/and) diabetes mellitus. METHODS: A total of 1440 participants were enrolled and divided into four groups, 330 in the hypertension group, 330 in the diabetes group, 300 in the hypertensive combined with diabetes group (combined disease group), and 480 in the healthy population group. Two doses of the COVID-19 vaccine (Vero cell), inactivated, were administered at a 21-day interval and blood samples were collected before vaccination and 28 days after the second dose to evaluate the immunogenicity. The adverse events and changes in blood pressure and blood glucose levels after vaccination were recorded. RESULTS: The seroconversion rate of the COVID-19 neutralizing antibodies was 100% for all participants. The post-inoculation geometric mean titer (GMT) in the four groups of the hypertension, diabetes, combined disease, and healthy populations were 73.41, 69.93, 73.84, and 74.86, respectively. The seroconversion rates and post-vaccination GMT in the hypertension, diabetes, and combined disease groups were non-inferior to the healthy population group. The rates of vaccine-related adverse reactions were 11.93%, 14.29%, 12.50%, and 9.38%, respectively. No serious adverse events were reported during the study. No apparent abnormal fluctuations in blood pressure and blood glucose values were observed after vaccination in participants with hypertension or(/and) diabetes. CONCLUSIONS: The COVID-19 vaccine (Vero cell), inactivated, showed good immunogenicity and safety in patients aged ≥60 years suffering from hypertension or(/and) diabetes mellitus.

Immunogenicity and safety of a live attenuated varicella vaccine in children 1-12 years of age: A randomized, blinded, controlled, non-inferiority phase 3 clinical trial.

OBJECTIVES: To evaluate the immunogenicity and safety of a live attenuated varicella vaccine produced using a cell factory process. METHODS: In this randomized, blinded, controlled, non-inferiority phase 3 clinical trial conducted in Guizhou, healthy children aged 1-12 years were randomly assigned in a 2: 1 ratio to receive one dose of experimental or control vaccine. Physical examination and first blood collection were performed preimmunization on day 0. Diary cards were collected after day 15. Contact cards and second blood samples were collected on day 30. The primary immunogenicity endpoint was the positive conversion rate of the anti-varicella virus antibody at 30 days postimmunization in susceptible children. Secondary endpoints were the fourfold increase rate, positive conversion rate, geometric mean titer, and geometric mean increase at 30 days after immunization in the total cohort. RESULTS: Of the 900 children assessed for eligibility, 894 received an experimental or control vaccine. Both the full analysis and safety analysis sets included 894 subjects. The seroconversion rate in the susceptible population was 95.84% in the experimental and 94.76% in the control group. The lower limit of the 95% confidence interval difference was -2.37%, which was greater than the non-inferiority margin set by the program (-10%). No significant difference in solicited adverse reactions was found between the groups. Within 6 months postimmunization, a total of 24 serious adverse events were reported, none related to the studied vaccine. CONCLUSION: The live attenuated varicella vaccine produced using a cell factory process was highly immunogenic, safe, and non-inferior to the product in the market. Further studies need to be implemented in the immune persistence, the epidemiological effectiveness and the rare adverse reactions.

Increasing vaccination coverage: The school entry vaccination record check program in Guizhou Province China, 2003-2018.

BACKGROUND: Guizhou Province of China implements a vaccination program specifying that children's vaccination records are to be checked upon entry to kindergarten and primary school; children missing one or more recommended vaccinations are to be offered the missed vaccinations; school-level vaccination coverage levels are assessed at the time of school enrollment and six months later to monitor compliance rates. METHODS: We obtained the number of doses of each vaccine in the national immunization schedule that were administered before and six months after kindergarten and school enrollment and reported to Guizhou Province during 2004 through 2018. We determined temporal trends in coverage of the second dose of measles-containing vaccine (MCV2) and other vaccines, incidence of measles, and number of school-based measles outbreaks. RESULTS: MCV2 coverage at kindergarten entry increased from 53% in 2004 to 98% in 2018. Among children missing one or more vaccinations, the six-month catch-up rate of MCV2 increased from 80% in 2004 to 99% in 2018. Among primary school children, coverage of MCV2 and other recommended vaccines had similar increases. The annual incidence of measles among Guizhou's total population declined from 280 per million in 2003 to 0.3 per million in 2018. There have been no measles outbreaks in kindergartens or schools since 2015. CONCLUSIONS: Checking vaccination record at kindergartens and primary schools and providing necessary catch-up vaccination was associated with increased coverage of measles and other vaccines, lower incidence of measles, and an apparent end to school-based measles outbreaks. Guizhou's experience of checking vaccination records at school enrollment led to implementation of this strategy in other provinces. In 2019, the kindergarten and school entry vaccination record check program was incorporated into China's national vaccine law.