Safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster following three doses of CoronaVac: a multicentre, open-label, phase 4, randomised trial

Tang, Rong; Zheng, Hui; Wang, Busen; Gou, Jin-Bo; Guo, Xiling; Chen, Xiaoqin; Chen, Yin; Wu, Shipo; Zhong, Jin; Pan, Hongxing; Zhu, Jiahong; Xu, Xiaoyu; Shi, Fengjuan; Li, Zhuo-Pei; Liu, Jingxian; Zhang, Xiaoyin; Cui, Lunbiao; Song, Zhizhou; Hou, Lihua; Zhu, Fengcai; Li, Jingxin; Huang, Hai-Tao; Li, Xiaolong; Wang, Xue; Wan, Peng; Zhu, Tao

doi:10.1016/s2213-2600(23)00049-8

Cited by 27 publications

(24 citation statements)

References 21 publications

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“…Full-text screening was performed for 20 articles, of which 5 articles did not meet the eligibility criteria and were excluded. A total of 15 studies [18][19][20][32][33][34][35][36][37][38][39][40][41][42][43] (11 analyzing safety, 13 analyzing immunogenicity, and 3 analyzing effective) were found to meet the inclusion criteria and were included in the systematic review and meta-analysis. The PRISMA flowchart depicted the process of article screening and selection (Figure 1).…”

Section: The Search Resultsmentioning

confidence: 99%

“…nAb responses were slightly superior for AAd5‐nCoV compared with IMAd5‐nCoV (SMD wt = 0.31, 95% CI: 0.14–0.48; SMD omicron = 0.35, 95% CI: 0.19–0.51), suggesting that nebulized dosing regimens are not inferior or even superior to intramuscular injections in the same vaccine platform. However, it has been shown that participants receiving intramuscular boosters had faster growth of nAb compared to the nebulized regimen 35 . Evidence from nonhuman primate studies 18 suggests that nebulized vaccines delivered through the mouth can induce a circulating humoral response more efficiently than intranasal delivery, can produce IgG antibodies that are ten times higher than those given intranasally, and have higher concentrations of IgA antibodies in bronchoalveolar lavage fluids, while using only a quarter of the dose of intranasal delivery regimens.…”

Section: Discussionmentioning

confidence: 99%

“…Data are available online for the included studies. [18][19][20][32][33][34][35][36][37][38][39][40][41][42][43]…”

Section: Conflict Of Interest Statementmentioning

confidence: 99%

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Safety, immunogenicity, and protective effective of inhaled COVID‐19 vaccines: A systematic review and meta‐analysis

Song,

Li,

Cheng

2024

Journal of Medical Virology

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This study aimed to examine the safety, immunogenicity and protective effective of inhaled COVID‐19 vaccines (ICVs). Literature research was done through EMBASE, Cochrane, PubMed, and Web of Science up to 10 March 2024. Pooled estimates with corresponding 95% confidence intervals (CI) were computed and compared using the random effects and common effects model. Of the 15 studies, 11 analyzed safety, 13 analyzed immunogenicity, and 3 analyzed protective effective. The results showed a favorable safety profile of ICVs for primary vaccination series, however it does not always seem to produce the expected immune response and protective effective. Meta‐analysis of ICVs booster vaccinations (BVs) showed that the levels of neutralizing antibody Geometric mean titer (nAb‐GMT) with aerosolised Ad5‐nCoV (AAd5‐nCoV) were all higher than those with inactivated vaccine (INA‐nCoV) (standard mean difference (SMD) = 2.32; 95% CI: 1.96–2.69) and intramuscular Ad5‐nCoV (IMAd5‐nCoV) (SMD = 0.31; 95% CI: 0.14–0.48) against the original strain of SARS‐CoV‐2. Importantly, we also observed similar results in the omicron variant. In addition, ICV in BVs has high mucosal immunity to IgA antibodies. The risk of adverse events was comparable or lower for AAd5‐nCoV compared to INA‐nCoV or IMAd5‐nCoV. Current evidence shows that the safety profile of ICVs were well. The booster dose of AAd5‐nCoV had a high immune response (including mucosal immunity) and provided protection against COVID‐19 caused by the SARS‐CoV‐2 omicron variant. Further studies are needed to investigate the long‐term safety of intranasal vaccine booster protection and various types of ICVs.

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Section: The Search Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Safety, immunogenicity, and protective effective of inhaled COVID‐19 vaccines: A systematic review and meta‐analysis

Song,

Li,

Cheng

2024

Journal of Medical Virology

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“…[49][50][51][52]75 Erosolized inhaled vaccines induce a mucosal immune response, and boosting with these vaccines theoretically aborts infections and prevents transmission. [76][77][78][79][80] Such studies performed particularly in children and adolescents to prevent the spread of SARS-CoV-2 or development of post-COVID-19 condition are required. 17,19,80 There are minimal data on optimal immunization for those with immunocompromized conditions and comorbidities, which are absolutely necessary for protecting these vulnerable, high-risk patients.…”

Section: Discussionmentioning

confidence: 99%

“…More studies are required to investigate whether different dosing schedules, including extended intervals between doses, heterologous prime‐boost, and intradermal administration, can improve immune responses while reducing the risks of myocarditis and pericarditis 49–52,75 . Erosolized inhaled vaccines induce a mucosal immune response, and boosting with these vaccines theoretically aborts infections and prevents transmission 76–80 . Such studies performed particularly in children and adolescents to prevent the spread of SARS‐CoV‐2 or development of post‐COVID‐19 condition are required 17,19,80 .…”

Section: Discussionmentioning

confidence: 99%

Immunogenicity of coronavirus disease 2019 vaccines in children: A review with ChatGPT

Leung

Duque

et al. 2023

Pediatric Discovery

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SARS‐CoV‐2 causes millions of infection cases and coronavirus disease 2019 (COVID‐19)‐related deaths worldwide. In addition to acute illnesses, children and adolescents suffer from post‐infectious complications. Vaccination is a promising preventative treatment that can confer protection from these devastating outcomes. Utilizing ChatGPT, this review discusses the immunogenicity of mRNA and inactivated COVID‐19 vaccines in children and adolescents. Rapid vaccine discovery during the COVID‐19 pandemic led to the approval of the mRNA vaccines that stimulate potent antibody responses in pediatric population, and the younger age groups develop higher neutralizing and non‐neutralizing antibody responses than those who are older. Natural infection induces weaker antibody responses than vaccination. Vaccine‐induced humoral immunity decreases over time, as antibodies decline six months after the second dose. However, antibody avidity increases, which partly maintains neutralization and Fc‐effector functions that provide more durable protection. Inactivated COVID‐19 vaccines generate strong antibody responses in children and adolescents. They induce T cell responses against multiple structural protein antigens, although their neutralizing antibody responses appear weaker and wane more quickly than mRNA vaccines. Full‐dose intradermal administration and heterologous prime‐boost may improve the immunogenicity of inactivated vaccines. In children and adolescents, immune protection from the pre‐Omicron variants of concern (VOCs) is maintained. Vaccination induces less antibody neutralization against the Omicron variant, but non‐neutralizing antibodies and T cell responses persist. Hybrid immunity provides stronger immunogenicity against SARS‐CoV‐2 in the pediatric population. Future research must focus on long‐term immunity, interaction with breakthrough reinfections, cross‐reactivity against new VOCs, T cell immunogenicity and immunogenicity in young children.

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Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

Rosa Duque,

Cheng,

Cohen

et al. 2023

World J Pediatr

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Background Optimising the immunogenicity of COVID-19 vaccines to improve their protection against disease is necessary. Fractional dosing by intradermal (ID) administration has been shown to be equally immunogenic as intramuscular (IM) administration for several vaccines, but the immunogenicity of ID inactivated whole severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the full dose is unknown. This study (NCT04800133) investigated the superiority of antibody and T-cell responses of full-dose CoronaVac by ID over IM administration in adolescents. Methods Participants aged 11–17 years received two doses of IM or ID vaccine, followed by the 3rd dose 13–42 days later. Humoral and cellular immunogenicity outcomes were measured post-dose 2 (IM-CC versus ID-CC) and post-dose 3 (IM-CCC versus ID-CCC). Doses 2 and 3 were administered to 173 and 104 adolescents, respectively. Results Spike protein (S) immunoglobulin G (IgG), S-receptor-binding domain (RBD) IgG, S IgG Fcγ receptor IIIa (FcγRIIIa)-binding, SNM [sum of individual (S), nucleocapsid protein (N), and membrane protein (M) peptide pool]-specific interleukin-2 (IL-2)+CD4+, SNM-specific IL-2+CD8+, S-specific IL-2+CD8+, N-specific IL-2+CD4+, N-specific IL-2+CD8+ and M-specific IL-2+CD4+ responses fulfilled the superior and non-inferior criteria for ID-CC compared to IM-CC, whereas IgG avidity was inferior. For ID-CCC, S-RBD IgG, surrogate virus neutralisation test, 90% plaque reduction neutralisation titre (PRNT90), PRNT50, S IgG avidity, S IgG FcγRIIIa-binding, M-specific IL-2+CD4+, interferon-γ+CD8+ and IL-2+CD8+ responses were superior and non-inferior to IM-CCC. The estimated vaccine efficacies were 49%, 52%, 66% and 79% for IM-CC, ID-CC, IM-CCC and ID-CCC, respectively. The ID groups reported more local, mild adverse reactions. Conclusion This is the first study to demonstrate superior antibody and M-specific T-cell responses by ID inactivated SARS-CoV-2 vaccination and serves as the basis for future research to improve the immunogenicity of inactivated vaccines. Graphical abstract

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Safety and immunogenicity of aerosolised Ad5-nCoV, intramuscular Ad5-nCoV, or inactivated COVID-19 vaccine CoronaVac given as the second booster following three doses of CoronaVac: a multicentre, open-label, phase 4, randomised trial

Cited by 27 publications

References 21 publications

Safety, immunogenicity, and protective effective of inhaled COVID‐19 vaccines: A systematic review and meta‐analysis

Safety, immunogenicity, and protective effective of inhaled COVID‐19 vaccines: A systematic review and meta‐analysis

Immunogenicity of coronavirus disease 2019 vaccines in children: A review with ChatGPT

Superior antibody and membrane protein-specific T-cell responses to CoronaVac by intradermal versus intramuscular routes in adolescents

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