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ImportancePeople over 60 developed less protection after two doses of inactivated COVID-19 vaccine than younger people. Heterologous vaccination might provide greater immunity and protection against variants of concern. ObjectiveTo assess the safety and immunogenicity of a heterologous immunization with an adenovirus type 5-vectored vaccine (Convidecia) among elderly who were primed with an inactivated vaccine (CoronaVac) previously. DesignAn observer-blind, randomized (1:1) trial, conducted from August 26 to November 13, 2021. SettingA single center in Jiangsu Province, China. Participants299 participants aged 60 years and older, of them 199 primed with two doses of CoronaVac in the past 3-6 months and 100 primed with one dose of CoronaVac in the past 1-2 months. InterventionConvidecia or CoronaVac as boosting dose Main Outcomes and MeasuresGeometric mean titers (GMTs) of neutralizing antibodies against wild-type SARS-CoV-2, and Delta and Omicron variants 14 days post boosting, and adverse reactions within 28 days. ResultsIn the three-dose regimen cohort (n=199; mean (SD) age, 66.7 (4.2) years; 74 (37.2%) female), 99 and 100 received a third dose of Convidecia (group A) and CoronaVac (group B), respectively. In the two-dose regimen cohort (n=100; mean (SD) age, 70.5 (6.0) years; 49 (49%) female), 50 and 50 received a second dose of Convidecia (group C) and CoronaVac (group D), respectively. GMTs of neutralizing antibodies against wild-type SARS-CoV-2 at day 14 were 286.4 (95% CI: 244.6, 335.2) in group A and 48.2 (95% CI: 39.5, 58.7) in group B, with GMT ratio of 6.2 (95% CI: 4.7, 8.1), and 70.9 (95% CI: 49.5, 101.7) in group C and 9.3 (95% CI: 6.2, 13.9) in group D, with GMT ratio of 7.6 (95% CI: 4.1, 14.1). There was a 6.3-fold (GMTs, 45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against Delta and Omicron variants in group A, respectively, compared with group B. However, there was no significant difference between group C and group D. Both heterologous and homologous booster immunizations were safe and well tolerated. Conclusions and RelevanceHeterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boost, without increasing safety concerns. Trial RegistrationClinicalTrials.gov NCT04952727 Key Points QuestionDoes a heterologous immunization with recombinant adenovirus type 5-vectored vaccine (Convidecia) produced a non-inferior or superior response of neutralizing antibodies among elderly primed with two doses of inactivated COVID-19 vaccine (CoronaVac), compared to the homologous boosting FindingsIn this randomized clinical trial, a heterologous third dose of Convidecia resulted in a 6.2-fold (geometric mean titers: 286.4 vs 48.2), 6.3-fold (45.9 vs 7.3) and 7.5-fold (32.9 vs 4.4) increase in neutralizing antibodies against wild-type strain, Delta and Omicron variants 14 days post boosting, respectively, compared to the homologous boost with CoronaVac MeaningHeterologous prime-boost regimens with CoronaVac and Convidecia induced strong neutralizing antibodies in elderly, which was superior to that induced by the homologous boosting.
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BackgroundHeterologous boost vaccination has been proposed as an option to elicit stronger and broader, or longer-lasting immunity. We assessed the safety and immunogenicity of heterologous immunization with a recombinant adenovirus type-5-vectored COVID-19 vaccine (Convidecia) and a protein-subunit-based COVID-19 vaccine (ZF2001). Methods and FindingsWe did a randomized, observer-blinded, placebo-controlled trial in healthy adults previously received one dose of Convidecia. Participants were randomly assigned (2:1) to receive either ZF2001 (vaccine group) or a trivalent inactivated influenza vaccine (TIV) (placebo group) at either 28-day or 56-day intervals. For both regimens, all participants received the 2nd injection with ZF2001 at 4 months after a dose of ZF2001 or TIV, with three-dose schedules of Convidecia/Convidecia/ZF2001 at day 0, day 28 and month 5 (referred to as CV/ZF/ZF (D0-D28-M5)) and CV/ZF/ZF (D0-D56-M6), and two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6). The primary outcome was the geometric mean titer (GMT) of the neutralizing antibodies against live SARS-CoV-2 virus 14 days after each boost vaccination. The safety outcome was 7-day reactogenicity, measured as solicited local or systemic adverse reactions after each vaccination. Between April 7, 2021, and May 6, 2021, 120 participants were enrolled, among whom 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 28-day interval, and 60 were randomly assigned to receive ZF2001 (n=40) or TIV (n=20) at a 56-day interval. 113 (94.2%) participants received the 2nd injection with ZF2001 4 months after a dose of ZF2001 or TIV. A total of 26 participants (21.7%) reported solicited adverse events within 7 days post boost vaccinations, and all the reported adverse reactions were mild. Among participants receiving ZF001 as second dose, the GMTs of neutralizing antibodies increased to 58.4 IU/ml (42.8-79.8) in 0-28 regimen, and to 80.8 IU/ml (53.1-122.9) in 0-56 regimen at 14 days post first boost dose. The GMTs of neutralizing antibodies increased to 334.9 IU/ml (95% CI 230.4, 486.9) in C/Z/Z (D0-D28-M5) regimen, and 441.2 IU/ml (260.8, 746.4) in C/Z/Z (D0-D56-M6) regimen at 14 days after the third dose. Two-dose schedules of CV/ZF (D0-M5) and CV/ZF (D0-M6) induced comparable antibody level comparable with that elicited by three-dose schedules, with the GMTs of 282.9 IU/ml (142.5, 561.8) and 293.9 IU/ml (137.6, 627.9), respectively. Study limitations include the absence of vaccine effectiveness in real-world, and current lack of immune persistence data and the neutralizing antibodies to Omicron. ConclusionsHeterologous boosting with ZF001 following primary vaccination of Convidecia is safe and more immunogenic than a single dose of Convidecia. These results support flexibility in cooperating viral vectored vaccines and recombinant protein vaccine. Trial RegistrationClinicalTrial.gov NCT04833101
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BackgroundThe safety and immunogenicity of heterologous prime-boost COVID-19 vaccine regimens with one shot of a recombinant adenovirus type-5-vectored COVID-19 vaccine Convidecia has not been reported. MethodsWe conducted a randomized, controlled, observer-blinded trial of heterologous prime-boost immunization with CoronaVac and Convidecia in healthy adults 18-59 years of age. Eligible participants who were primed with one or two doses of CoronaVac were randomly assigned at a 1:1 ratio to receive a booster dose of Convidecia or CoronaVac. Participants were masked to the vaccine received but not to the three-dose or two-dose regimen. The occurrences of adverse reactions within 28 days after the vaccination were documented. The geometric mean titers of neutralizing antibodies against live SARS-CoV-2 virus were measured at 14 and 28 days after the booster vaccination. ResultsBetween May 25 and 26, 2021, a total of 300 participants were enrolled. Participants who received a booster shot with a heterologous dose of Convidecia reported increased frequencies of solicited injection-site reactions than did those received a homogeneous dose of CoronaVac, but frequencies of systemic reactions. The adverse reactions were generally mild to moderate. The heterologous immunization with Convidecia induced higher live viral neutralizing antibodies than did the homogeneous immunization with CoronaVac (197.4[167.7, 232.4] vs. 33.6[28.3, 39.8] and 54.4[37. 9, 78.0] vs. 12.8[9.3, 17.5]) at day 14 in the three- and two-dose regimen cohort, respectively. ConclusionsThe heterologous prime-boost regimen with Convidecia after the priming with CoronaVac was safe and significantly immunogenic than a homogeneous boost with CoronaVac (ClinicalTrials.gov, number NCT04892459).
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Objective To investigate the correlation between long non-coding RNA (lncRNA)-LOC391533 and inadequate placental spiral artery remodeling in severe preeclampsia (sPE).Methods Thirty-six gravidas who were admitted to the Third Affiliated Hospital of Zhengzhou University with sPE from January 2016 to December 2016 were enrolled in sPE group.An equal number of healthy gravidas who experienced uneventful pregnancy and were of similar age (difference less than two years) and gestational age (difference less than one week) to those in the sPE group served as controls.Scanning electron microscopy was used to measure the luminal area and vessel wall thickness of placental spiral arteries for all gravidas.Levels of vascular endothelial growth factor (VEGF) and soluble VEGF receptor-1 (sVEGFR-1) in placenta tissues and maternal serum samples were detected by Western blot and ELISA.Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of LOC391533 at mRNA level in placenta tissues of the two groups.Independent two samples t-test,Mann-Whitney U test and Spearman correlation analysis were used for statistical analysis.Results (1) The average luminal area of spiral arteries of the sPE group was smaller than that of the control group [(130.1 22.3) vs (188.1 ±21.5) μ m2,t=10.888,P＜0.05],but the average thickness of spiral artery wall was thicker [(122.619.5) vs (98.9±2.5) μ m,t=-8.812,P＜0.05].(2) Compared with the control group,the sPE group showed increased sVEGFR-1 at protein level in both placenta tissues and serum samples [placenta:0.2±0.0 vs 0.4±0.1,serum:(15.6±2.4) vs (50.8±6.1) ng/L,t=-17.569 and-30.699,both P＜0.05],decreased VEGF at protein level in both placenta tissues and serum samples [placenta:0.6 ± 0.1 vs 0.2±0.0,serum:(40.8±3.2) vs (28.1 ±3.2) ng/L,t=18.013 and 16.200,both P＜0.05],and enhanced expression of LOC391533 at mRNA level in placenta tissues (1.00.2 vs 2.40.5,t=-14.799,P＜0.05).(3) Expression of LOC391533 at mRNA level in placenta tissues of the sPE group was positively correlated with spiral artery wall thickness and levels of sVEGFR-1 protein in placenta tissues and serum (r=0.683,0.759 and 0.857,all P＜0.05),and negatively correlated with luminal area and levels of VEGF protein in placenta tissues and serum (r=-0.702,-0.806 and-0.796,all P＜0.05).Conclusions Abnormal expression of VEGF and sVEGF-1 in placenta and serum of patients with sPE may be related to inadequate placental spiral artery remodeling.
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Objective To establish a double-antibody sandwich ELISA for the rapid detection of shiga toxin typeⅡ ( StxⅡ) in shiga toxin-producing Escherichia coli ( STEC) infection. Methods A pool of murine hybridomas was used to screen out the optimal antibody pair for the establishment of double-anti-body sandwich ELISA. The established ELISA system was used to detect StxⅡin the culture supernatants of 16 clinical strains of STEC. Specificity and sensitivity of the established ELISA system were also evaluated. Results Two antibodies, S2D8 and S2C6, were successfully screened out, based on which the double-anti-body sandwich ELISA was set up. StxⅡand its variants rather than StxⅠwas detected in the culture super-natants of STEC with a lowest detection limit of 4 ng/ml. Its performance was consistent with that of commer-cial colloidal gold test kit, indicating the characteristics of good specificity and sensitivity. Conclusion The S2D8/S2C6-based ELISA laid a foundation for researches which designates the shiga toxin as a potential can-didate on the diagnosis and therapy of STEC infection.
