Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

Zhang, Zhe; Wu, Shipo; Liu, Yawei; Li, Kailiang; Fan, Pengfei; Song, Xiaohong; Wang, Yudong; Zhao, Zeyao; Zhang, Xianwei; Shang, Jian Ku; Zhang, Jinlong; Xu, Jinhan; Li, Yao; Li, Yaohui; Zhang, Jipeng; Fu, Kefan; Wang, Busen; Hao, Meng; Zhang, Guanying; Long, Pengwei; Qiu, Ziyu; Zhu, Tao; Liu, Shilin; Zhang, Yue; Shao, Fangze; Lv, Peng; Yang, Yilong; Zhao, Xiaofan; Sun, Yan; Hou, Lihua; Chen, Wei

doi:10.1101/2022.03.08.22271816

Cited by 18 publications

(25 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“… 17 – 19 Another two booster vaccination studies illustrated that the pseudo-virus neutralizing antibody titers against wild-type SARS-CoV-2 strain and Omicron variant elicited by ZF2001 booster following two-dose inactivated vaccines were 2.2–3.3-fold and 1.6–2.5-fold higher, respectively, than those induced by a homologous booster of inactivated vaccines. 20 , 21 A nationwide cohort study conducted in Sweden showed that the effectiveness against symptomatic COVID-19 infection was 67% and 79% for the heterologous ChAdOx1/BNT162b2 and ChAdOx1/mRNA-1273 prime-boost vaccinations, respectively, which were higher than 50% of the homologous ChAdOx1 vaccination. 14 The preliminary analysis results of a phase III clinical trial demonstrated that after a heterologous booster vaccination of the recombinant protein subunit vaccine V-01 in inactivated vaccine recipients, the person-year incidence rate of SARS-CoV-2 infections was reduced from 12.80% to 6.73%, and the absolute protective efficacy was 61.35% ( https://en.livzon.com.cn/companyfile/1029.html ).…”

Section: Discussionmentioning

confidence: 99%

“… 11 – 13 Besides the homologous boosting, heterologous booster strategy has also attracted great concerns, and multiple clinical trials and cohort studies have shown that the immune response elicited by heterologous prime-booster vaccination was significantly greater than that induced by homologous counterparts. 14 – 21 Currently, several clinical trials have been conducted to evaluate the safety, immunogenicity and efficacy of a heterologous booster dose of recombinant subunit vaccines, such as V-01 (NCT05096832), ZF2001 (NCT05205096, NCT05205083) and SCB-2019 (NCT05087368), following two-dose inactivated vaccines. Some preliminary study results have demonstrated that the heterologous booster of recombinant protein subunit vaccines distinctly improved the neutralizing antibody level 17 – 21 and protective efficacy ( https://en.livzon.com.cn/companyfile/1029.html ) against various SARS-CoV-2 strains, including the Omicron variant, which was immunogenically superior to the homologous booster of inactivated vaccines.…”

Section: Introductionmentioning

confidence: 99%

“…Some preliminary study results have demonstrated that the heterologous booster of recombinant protein subunit vaccines distinctly improved the neutralizing antibody level 17 – 21 and protective efficacy ( https://en.livzon.com.cn/companyfile/1029.html ) against various SARS-CoV-2 strains, including the Omicron variant, which was immunogenically superior to the homologous booster of inactivated vaccines. 17 – 21 …”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial

Kaabi

Yang²,

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

The increased coronavirus disease 2019 (COVID-19) breakthrough cases pose the need of booster vaccination. We conducted a randomised, double-blinded, controlled, phase 2 trial to assess the immunogenicity and safety of the heterologous prime-boost vaccination with an inactivated COVID-19 vaccine (BBIBP-CorV) followed by a recombinant protein-based vaccine (NVSI-06-07), using homologous boost with BBIBP-CorV as control. Three groups of healthy adults (600 individuals per group) who had completed two-dose BBIBP-CorV vaccinations 1–3 months, 4–6 months and ≥6 months earlier, respectively, were randomly assigned in a 1:1 ratio to receive either NVSI-06-07 or BBIBP-CorV boost. Immunogenicity assays showed that in NVSI-06-07 groups, neutralizing antibody geometric mean titers (GMTs) against the prototype SARS-CoV-2 increased by 21.01–63.85 folds on day 28 after vaccination, whereas only 4.20–16.78 folds of increases were observed in control groups. For Omicron variant, the neutralizing antibody GMT elicited by homologous boost was 37.91 on day 14, however, a significantly higher neutralizing GMT of 292.53 was induced by heterologous booster. Similar results were obtained for other SARS-CoV-2 variants of concerns (VOCs), including Alpha, Beta and Delta. Both heterologous and homologous boosters have a good safety profile. Local and systemic adverse reactions were absent, mild or moderate in most participants, and the overall safety was quite similar between two booster schemes. Our findings indicated that NVSI-06-07 is safe and immunogenic as a heterologous booster in BBIBP-CorV recipients and was immunogenically superior to the homologous booster against not only SARS-CoV-2 prototype strain but also VOCs, including Omicron.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial

Kaabi

Yang²,

Zhang

et al. 2022

Sig Transduct Target Ther

View full text Add to dashboard Cite

show abstract

“…Table 2 summarizes the geometric mean titer (GMT) following homologous and heterologous vaccination against different COVID-19 variants in the current studies (63,(72)(73)(74)(75)(76)(77)(78). It is noteworthy that levels of neutralizing antibodies produced in populations receiving a heterologous booster after two doses of inactivated viral vaccines are higher than that of the homologous group.…”

Section: Booster Vaccination Strategymentioning

confidence: 99%

The importance of booster vaccination in the context of Omicron wave

Wei

Wang

et al. 2022

Front. Immunol.

View full text Add to dashboard Cite

Omicron (B.1.1.529) was first detected in a sample collected in Botswana on November 11, 2021, and has rapidly replaced Delta as the dominant global variant given the robust transmissibility. Moreover, it displays a lower virulence than other variants. However, the pathogenicity of Omicron appears to be underestimated in view of the increasing levels of herd immunity through natural infection or vaccination. Additionally, the volume of hospitalizations and deaths increase in proportion to the number of cases due to the high transmissibility of Omicron. Therefore, vaccination remains an important public health priority. Notably, a series of important mutations in the Omicron spike protein, especially in the receptor-binding domain and N-terminal domain, appears to be associated with immune escape capacity, reducing the willingness of people to receive vaccines. Herein, we provide an in-depth discussion to assess the effectiveness of the second and third vaccination against Omicron variant. On the one hand, the two-dose vaccination program adopted by many countries is insufficient to prevent Omicron infection given the mutations correlated with immune escape and the decline in vaccine efficacy over time. On the other hand, booster dose significantly increases the protective efficacy against Omicron infection. Most importantly, heterologous third dose vaccination induces a more robust immune response than homologous booster dose. Therefore, under the special background of this pandemic, there is an urgent need to accelerate the third dose of vaccination, especially providing better booster vaccination strategies, to combat emerging Omicron variant.

show abstract

“…More than 250 COVID-19 vaccines are currently being developed,4 and over 90 vaccines are developed in the middle and late clinical research stages 5. At present, there are three kinds and five brands of COVID-19 vaccines approved for listing with conditions in China: inactivated vaccines (produced by Beijing Institute of Biological Products and Wuhan Institute of Biological Products under China Biotechnology of China Pharmaceutical Group, and Sinovac Biotech), adenovirus vector vaccine (produced by CanSino Biologics) and recombinant COVID-19 vaccine (produced by Zhi Fei Long Ke Ma Biopharmaceutical) 6 7. Most of the approved COVID-19 vaccines are in emergency use or listed with conditions, and the data on the effectiveness of the vaccines are mainly derived from clinical trial results 8–23.…”

Section: Introductionmentioning

confidence: 99%

Urban monitoring, evaluation and application of COVID-19 listed vaccine effectiveness: a health code blockchain study

Wang

Li³

et al. 2022

BMJ Open

View full text Add to dashboard Cite

ObjectiveBy using health code blockchain, cities can maximise the use of personal information while maximising the protection of personal privacy in the monitoring and evaluation of the effectiveness of listed vaccines.DesignThis study constructs an urban COVID-19 listed vaccine effectiveness (VE) monitoring, evaluation and application system based on the health code blockchain. This study uses this system and statistical simulation to analyse three urban application scenarios, namely evaluating the vaccination rate (VR) and determining the optimal vaccination strategy, evaluating herd immunity and monitoring the VE on variant.Main outcome measuresThe primary outcomes first establish an urban COVID-19 listed VE monitoring, evaluation and application system by using the health code blockchain, combined with the dynamic monitoring model of VE, the evaluation index system of VE and the monitoring and evaluation system of personal privacy information use, and then three measures are analysed in urban simulation: one is to take the index reflecting urban population mobility as the weight to calculate the comprehensive VR, the second is to calculate the comprehensive basic reproduction number (R) in the presence of asymptomatic persons, the third is to compare the difference between the observed effectiveness and the true effectiveness of listed vaccines under virus variation.ResultsCombining this system and simulation, this study finds: (1) The comprehensive VR, which is weighted to reflect urban population mobility, is more accurate than the simple VR which does not take into account urban population mobility. Based on population mobility, the algorithm principle of urban optimal vaccination strategy is given. In the simulation of urban listed vaccination involving six regions, programmes 1 and 5 have the best protective effect among the eight vaccination programmes, and the optimal vaccination order is 3-5-2-4-6-1. (2) In the presence of asymptomatic conditions, the basic reproduction number, namely R0*(1-VR*VE), does not accurately reflect the effect of herd immunity, but the comprehensive basic reproduction number (R) should be used. The R is directly proportional to the proportion of asymptomatic people (aw) and the duration of the incubation period (ip), and inversely proportional to the VR, the VE and the number of days transmitted in the ip (k). In the simulation analysis, when symptomatic R0=3, even with aw=0.2, the R decreases to nearly 1 until the VR reaches 95%. When aw=0.8, even when the entire population is vaccinated, namely VR=1, the R is 1.688, and still significantly greater than 1. If the R is to be reduced to 1, the VE needs to be increased to 0.87. (3) This system can more comprehensively and accurately grasp the impact of the variant virus on urban VE. The traditional epidemiological investigation can lose the contacts of infected persons, which leads to the deviation between the observed effectiveness and the true effectiveness. Virus variation aggravates the loss, and then increases the deviation. Simulation case 1 assumes the unvaccinated rate of 0.8, the ongoing VR of 0.1, the completed VR of 0.1 and an average infection rate of 2% for the variant virus. If a vaccine is more than 90% effectiveness against the premutant virus, but only 80% effectiveness against the mutant virus, and because 80% of the unvaccinated people who are not infected are not observed, the observed effectiveness of the vaccine is 91.76%, it will lead to the wrong judgement that the VE against the variant virus is not decreased. Simulation case 2 assumes the unvaccinated rate of 0.8, the ongoing VR of 0.1, the completed VR of 0.1 and an average infection rate of 5% for the variant virus. Simulation finds that the higher the proportion of unvaccinated infected people who are not observed, the lower the estimate of observed effectiveness; and the lower the true effectiveness, the larger the gap between observed effectiveness and true effectiveness. Simulation case 3 assumes the unvaccinated rate of 0.2, the ongoing VR of 0.2, the completed VR of 0.6 and an average infection rate of 2% for the variant virus. Simulation finds that the higher the proportion of unobserved completed vaccination patients who are not infected, the lower the estimate of observed effectiveness; and the lower the true effectiveness, the larger the gap between observed effectiveness and true effectiveness. Simulation case 4 assumes the unvaccinated rate of 0.2, the ongoing VR of 0.2, the completed VR of 0.6 and an average infection rate of 5% for the variant virus. If a vaccine is more than 90% effectiveness against the premutant virus, but only 80% effectiveness against the mutant virus, and because 80% of the infected people with complete vaccination are not observed, the observed effectiveness of the vaccine is 91.95%, similar to case 1, it will lead to the wrong judgement that the VE against the variant virus is not decreased.ConclusionCompared with traditional epidemiological investigation, this system can meet the challenges of accelerating virus variation and a large number of asymptomatic people, dynamically monitor and accurately evaluate the effectiveness of listed vaccines and maximise personal privacy without locking down the relevant area or city. This system established in this study could serve as a universal template for monitoring and evaluating the effectiveness of COVID-19 listed vaccines in cities around the world. If this system can be promoted globally, it will promote countries to strengthen unity and cooperation and enhance the global ability to respond to COVID-19.

show abstract

Aerosolized Ad5-nCoV booster vaccination elicited potent immune response against the SARS-CoV-2 Omicron variant after inactivated COVID-19 vaccine priming

Cited by 18 publications

References 35 publications

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial

Immunogenicity and safety of NVSI-06-07 as a heterologous booster after priming with BBIBP-CorV: a phase 2 trial

The importance of booster vaccination in the context of Omicron wave

Urban monitoring, evaluation and application of COVID-19 listed vaccine effectiveness: a health code blockchain study

Contact Info

Product

Resources

About