Factors associated with neutralizing antibody levels induced by two inactivated COVID-19 vaccines for 12 months after primary series vaccination.

Background: BBIBP-CorV and CoronaVac inactivated COVID-19 vaccines are widely-used, World Health Organization-emergency-listed vaccines. Understanding antibody level changes over time after vaccination is important for booster dose policies. We evaluated neutralizing antibody (nAb) titers and associated factors for the first 12 months after primary-series vaccination with BBIBP-CorV and CoronaVac. Methods: Our study consisted of a set of cross-sectional sero-surveys in Zhejiang and Shanxi provinces, China. In 2021, we enrolled 1,527 consenting 18-59-year-olds who received two doses of BBIBP-CorV or CoronaVac 1, 3, 6, 9, or 12 months earlier and obtained blood samples and demographic and medical data. We obtained 6-month convalescent sera from 62 individuals in Hebei province. Serum nAb titers were measured by standard micro-neutralization cytopathic effect assay in Vero cells with ancestral SARS-CoV-2 strain HB01. We used the first WHO International Standard (IS) for anti-SARS-CoV-2 immunoglobulin (NIBSC code 20/136) to standardized geometric mean concentrations (IU/mL) derived from the nAb geometric mean titers (GMT over 1:4 was considered seropositive). We analyzed nAb titer trends using Chi-square and factors related to nAb titers with logistic regression and linear models. Results: Numbers of subjects in each of the five month-groupings ranged from 100 to 200 for each vaccine and met group-specific target sample sizes. Seropositivity rates from BBIBP-CorV were 98.0% at 1 month and 53.5% at 12 months, and GMTs were 25.0 and 4.0. Respective seropositivity rates from CoronaVac were 90.0% and 62.5%, and GMTs were 20.2 and 4.1. One-, three-, six-, nine-, and twelve-month GMCs were 217.2, 84.1, 85.7, 44.6, and 10.9 IU/mL in BBIBP-CorV recipients and 195.7, 94.6, 51.7, 27.6, and 13.4 IU/mL in CoronaVac recipients. Six-month convalescent seropositivity was 95.2%; GMC was 108.9 IU/mL. Seropositivity and GMCs were associated with age, sex, and time since vaccination. Conclusions: Neutralizing Ab levels against ancestral SARS-CoV-2 from BBIBP-CorV or CoronaVac vaccination were similar and decreased with increasing time since vaccination; over half of 12-month post-vaccination subjects were seropositive. Seropositivity and GMCs from BBIBP-CorV and CoronaVac six and nine months after vaccination were similar to or slightly lower than in six-month convalescent sera. These real-world data suggest necessity of six-month booster doses.

Immunogenicity and safety of an inactivated SARS-CoV-2 vaccine (Sinopharm BBIBP-CorV) coadministered with quadrivalent split-virion inactivated influenza vaccine and 23-valent pneumococcal polysaccharide vaccine in China: A multicentre, non-inferiority, open-label, randomised, controlled, phase 4 trial.

BACKGROUND: The safety and immunogenicity of the coadministration of an inactivated SARS-CoV-2 vaccine (Sinopharm BBIBP-CorV), quadrivalent split-virion inactivated influenza vaccine (IIV4), and 23-valent pneumococcal polysaccharide vaccine (PPV23) in adults in China is unknown. METHODS: In this open-label, non-inferiority, randomised controlled trial, participants aged ≥ 18 years were recruited from the community. Individuals were eligible if they had no history of SARS-CoV-2 vaccine or any pneumonia vaccine and had not received an influenza vaccine during the 2020-21 influenza season. Eligible participants were randomly assigned (1:1:1), using block randomization stratified, to either: SARS-CoV-2 vaccine and IIV4 followed by SARS-CoV-2 vaccine and PPV23 (SARS-CoV-2 + IIV4/PPV23 group); two doses of SARS-CoV-2 vaccine (SARS-CoV-2 vaccine group); or IIV4 followed by PPV23 (IIV4/PPV23 group). Vaccines were administered 28 days apart, with blood samples taken on day 0 and day 28 before vaccination, and on day 56. RESULTS: Between March 10 and March 15, 2021, 1152 participants were recruited and randomly assigned to three groups (384 per group). 1132 participants were included in the per-protocol population (375 in the SARS-CoV-2 + IIV4/PPV23 group, 380 in the SARS-CoV-2 vaccine group, and 377 in the IIV4/PPV23 group). The seroconversion rate (100 % vs 100 %) and GMT (159.13 vs 173.20; GMT ratio of 0.92 [95 % CI 0.83 to 1.02]) of SARS-CoV-2 neutralising antibodies in the SARS-CoV-2 + IIV4/PPV23 group was not inferior to those in the SARS-CoV-2 vaccine group. The SARS-CoV-2 + IIV4/PPV23 group was not inferior to the IIV4/PPV23 group in terms of seroconversion rates and GMT of influenza virus antibodies for all strains except for the seroconversion rate for the B/Yamagata strain. The SARS-CoV-2 + IIV4/PPV23 group was not inferior to the IIV4/PPV23 group regarding seroconversion rates and GMC of Streptococcus pneumoniae IgG antibodies specific to all serotypes. All vaccines were well tolerated. CONCLUSIONS: The coadministration of the inactivated SARS-CoV-2 vaccine and IIV4/PPV23 is safe with satisfactory immunogenicity. This study is registered with ClinicalTrials.gov, NCT04790851.

Immunogenicity and Safety of an Inactivated Enterovirus 71 Vaccine Administered Simultaneously with Hepatitis B Virus Vaccine, Group A Meningococcal Polysaccharide Vaccine, Measles-Rubella Combined Vaccine and Japanese Encephalitis Vaccine: A Multi-Center, Randomized, Controlled Clinical Trial in China.

BACKGROUND: The aim of this study was to investigate the immunogenicity and safety of the enterovirus 71 vaccine (EV71 vaccine) administered alone or simultaneously. METHODS: A multi-center, open-label, randomized controlled trial was performed involving 1080 healthy infants aged 6 months or 8 months from Shandong, Shanxi, Shaanxi, and Hunan provinces. These infants were divided into four simultaneous administration groups and EV71 vaccine separate administration group. Blood samples were collected from the infants before the first vaccination and after the completion of the vaccination. This trial was registered in the Clinical Trials Registry (NCT03519568). RESULTS: A total of 895 were included in the per-protocol analysis. The seroconversion rates of antibodies against EV71 in four simultaneous administration groups (98.44% (189/192), 94.57% (122/129), 99.47% (187/188) and 98.45% (190/193)) were non-inferior to EV71 vaccine separate administration group (97.93% [189/193]) respectively. Fever was the most common adverse event, the pairwise comparison tests showed no difference in the incidence rate of solicited, systemic or local adverse events. Three serious adverse events related to the vaccination were reported. CONCLUSIONS: The evidence of immunogenicity and safety supports that the EV71 vaccine administered simultaneously with vaccines need to be administered during the same period of time recommended in China.

Immunogenicity and safety of different sequential schedules of Sabin strain-based inactivated poliovirus vaccination: A randomized, controlled, open-label, phase IV clinical trial in China.

BACKGROUND: The immunogenicity and safety of the sequential schedule of Sabin strain-based inactivated poliovirus vaccine (sIPV) and bivalent oral poliovirus vaccine (bOPV) remains poorly understood in Chinese population. METHODS: A multi-center, open-label, randomized controlled trial was performed involving 648 healthy infants aged 2 months from Inner Mongolia, Shanxi, and Hebei provinces. These participants were divided into three groups: sIPV-bOPV-bOPV, sIPV-sIPV-bOPV, and sIPV-sIPV-sIPV. Doses were administered sequentially at age 2, 3, and 4 months. Neutralisation assays were tested using sera collected at 2 months and 5 months. RESULTS: A total of 569 were included in the per-protocol analysis. The seroconversion rates of poliovirus type 1 and 3 were 100% in all three groups, the seroconversion rate of poliovirus type 2 was 91.53% (173/189) (95% CI: 86.62-95.08) in the sIPV-bOPV-bOPV group, 98.38% (182/185) (95% CI: 95.33-99.66) in the sIPV-sIPV-bOPV group, and 99.49% (194/195) (95% CI: 97.18-99.99) in the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus types 1 and 3, the sIPV-bOPV-bOPV and sIPV-sIPV-bOPV groups were non-inferior to the sIPV-sIPV-sIPV group. For the seroconversion rate of poliovirus type 2, the sIPV-sIPV-bOPV group was non-inferior to the sIPV-sIPV-sIPV group, and the sIPV-bOPV-bOPV group was inferior to the sIPV-sIPV-sIPV group. All three groups exhibited good safety, with two serious adverse events reported, that were unrelated to vaccine. CONCLUSIONS: In china, a new vaccination schedule that including 2 doses of IPV in the national immunization programs is essential. Trial registration ClinicalTrials.govNCT04054492.

Multiplex microfluidic paper-based immunoassay for the diagnosis of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is a serious and rising global healthcare problem. One critical challenge to tackle this disease is the lack of adequate diagnosis. Here, we develop a multiplex microfluidic paper-based immunoassay, as a novel diagnostic approach, to detect human IgG antibody against HCV (anti-HCV). The paper substrate, highly flammable nitrocellulose (NC), is patterned under ambient temperature by craft punch patterning (CPP) to generate multiple test zones. On the basis of superior merits of patterned paper, this new diagnostic approach demonstrates the key novelty to unprecedentedly combine segmented diagnostic assays into a single multiplex test. The generated diagnostic results are not only informative but can be rapidly and cost-effectively delivered. It would significantly transform the clinical pathway for unwitting individuals with HCV infection. This work highlights the promising role of microfluidic paper-based immunoassays in tackling the diagnostic challenge for the HCV pandemic as well as other diseases.