Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity

Leung, Daniel; Mu, Xiaofeng; Duque, Jaime S. Rosa; Cheng, Samuel; Wang, Manni; Zhang, Wenyue; Zhang, Yanmei; Tam, Issan Y. S.; Lee, Toby S. S.; Lam, Jennifer H. Y.; Chan, Sau Man; Cheang, Cheuk Hei; Chung, Yuet; Wong, Howard H. W.; Lee, Amos M. T.; Li, Wing Yan; Chaothai, Sara; Tsang, Leo C. H.; Chua, Gilbert T.; Cheong, Kai-Ning; Au, Elaine; Kwok, Janette; Chan, Koon Wing; Chong, Patrick C. Y.; Lee, Pamela; Ho, Mandy; Lee, Tsz Leung; Tu, Wenwei; Peiris, Malik; Lau, Yu Lung

doi:10.3389/fimmu.2022.982155

Cited by 9 publications

(20 citation statements)

References 45 publications

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“…Several studies in general population have raised the importance of booster for a greater protection against SARS-CoV-2 infection and leads to reduce disease severity. Among IEI patients the third doses of BNT162b2 reduces the seroconversion failure from 45% to 26% ( 37 ), similar results from Shields et al, reducing the seroconversion failure from 39 to 34% in IEI patients ( 38 ). However, there are still some IEI patients that failed to produce antibody response or a T cell response.…”

Section: Discussionsupporting

confidence: 66%

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination

et al. 2023

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IntroductionInborn errors of immunity (IEI) are a heterogeneous group of diseases caused by intrinsic defects of the immune system. Estimating the immune competence of immunocompromised patients for an infection risk assessment or after SARS-CoV-2 vaccination constituted a challenge.MethodsThe aim of this study was to determine the humoral responses of patients with IEI through a comprehensive analysis of specific receptor-binding domain-positive (RBD+) IgG+ memory B cells (MBCs) by flow cytometry, together with routine S-specific IgG antibodies and QuantiFERON SARS-CoV-2 (T-cell response), before the vaccine and 3 weeks after a second dose.Results and discussionWe first analyzed the percentage of specific RBD+ IgG+ MBCs in healthy healthcare workers. Within the control group, there was an increase in the percentage of specific IgG+ RBD+ MBCs 21 days after the second dose, which was consistent with S-specific IgG antibodies.Thirty-one patients with IEI were included for the pre- and post-vaccination study; IgG+ RBD+ MBCs were not evaluated in 6 patients due to an absence of B cells in peripheral blood. We detected various patterns among the patients with IEI with circulating B cells (25, 81%): an adequate humoral response was observed in 12/25, consider by the detection of positive S-specific IgG antibodies and the presence of specific IgG+ RBD+ MBCs, presenting a positive T-cell response; in 4/25, very low S-specific IgG antibody counts correlated with undetectable events in the IgG+ RBD+ MBC compartment but with positive cellular response. Despite the presence of S-specific IgG antibodies, we were unable to detect a relevant percentage of IgG+ RBD+ MBCs in 5/25; however, all presented positive T-cell response. Lastly, we observed a profound failure of B and T-cell response in 3 (10%) patients with IEI, with no assessment of S-specific IgG antibodies, IgG+ RBD+ MBCs, and negative cellular response. The identification of specific IgG+ RBD+ MBCs by flow cytometry provides information on different humoral immune response outcomes in patients with IEI and aids the assessment of immune competence status after SARS-CoV-2 mRNA vaccine (BNT162b2), together with S-specific IgG antibodies and T-cell responses.

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Section: Discussionsupporting

confidence: 66%

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination

et al. 2023

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“…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 81–84 . As primary vaccination rates have peaked with satisfactory coverage in most geographical regions by this time, newer generations of polyvalent vaccines must be thoroughly investigated in the future, especially in unvaccinated infants who have not been exposed to the virus on which there is currently minimal research 1,49–52,85 .…”

Section: Discussionmentioning

confidence: 99%

“…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. [81][82][83][84] As primary vaccination rates have peaked with satisfactory coverage in most geographical regions by this time, newer generations of polyvalent vaccines must be thoroughly investigated in the future, especially in unvaccinated infants who have not been exposed to the virus on which there is currently minimal research. 1,[49][50][51][52]85 This will be essential to inform policymakers on their decision to incorporate COVID-19 vaccines in national immunization programs.…”

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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“…When the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic broke out in late 2019 [ 8 ], initial reports indicated increased disease-related morbidity and mortality in immunocompromised patients [ 9 , 10 , 11 , 12 , 13 ], including those with PAD [ 14 , 15 , 16 ]. After vaccines became available, several studies have investigated both the reactogenicity and immunogenicity of SARS-CoV-2 vaccines in PAD patients, and most studies concluded that the immune response in PAD patients was inferior to that in healthy vaccine recipients [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ].…”

Section: Introductionmentioning

confidence: 99%

“…Several studies with immunocompetent individuals have examined the correlates of SARS-CoV-2-specific humoral response and found changes in levels of M-CSF, IL-1α, IFN-γ, IL-1β, IL-10, IL-12p70, IL-6, IL-17A, IL-15, and IFN signaling-related cytokines (CXCL10, MCP-1, MCP-2, and MCP-3) to be correlated with SARS-CoV-2-specific antibody response in healthy volunteers [ 45 , 62 , 63 , 64 , 65 ]. Regarding PAD patients, several studies have examined the T cell response role in protection against SARS-CoV-2, showing IL-2 and/or IFN-γ secretion in response to pooled SARS-CoV-2 antigens [ 18 , 24 , 25 , 26 , 27 , 28 ]. Nonetheless, the understanding of the wider range of cytokines produced following SARS-CoV-2 antigen stimulation in individuals with predominantly antibody deficiencies is currently limited.…”

Section: Introductionmentioning

confidence: 99%

Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies

Lucane

Šlisere

Gersone

et al. 2023

Viruses

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Predominantly antibody deficiencies (PADs) are inborn disorders characterized by immune dysregulation and increased susceptibility to infections. Response to vaccination, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), may be impaired in these patients, and studies on responsiveness correlates, including cytokine signatures to antigen stimulation, are sparse. In this study, we aimed to describe the spike-specific cytokine response following whole-blood stimulation with SARS-CoV-2 spike peptides in patients with PAD (n = 16 with common variable immunodeficiency and n = 15 with selective IgA deficiency) and its relationship with the occurrence of coronavirus disease 2019 (COVID-19) during up to 10-month follow-up period. Spike-induced antibody and cytokine production was measured using ELISA (anti-spike IgG, IFN-γ) and xMAP technology (interleukin-1β (IL-1β), IL-4, IL-6, IL-10, IL-15, IL-17A, IL-21, TNF-α, TGF-β1). No difference was found in the production of cytokines between patients with PAD and controls. Anti-spike IgG and cytokine levels did not predict contraction of COVID-19. The only cytokine that distinguished between vaccinated and naturally infected unvaccinated PAD patients was IFN-γ (median 0.64 (IQR = 1.08) in vaccinated vs. 0.10 (IQR = 0.28) in unvaccinated). This study describes the spike-specific cytokine response to SARS-CoV-2 antigens, which is not predictive of contracting COVID-19 during the follow-up.

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Safety and immunogenicity of 3 doses of BNT162b2 and CoronaVac in children and adults with inborn errors of immunity

Cited by 9 publications

References 45 publications

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination

Detection of specific RBD+ IgG+ memory B cells by flow cytometry in healthcare workers and patients with inborn errors of immunity after BNT162b2 m RNA COVID-19 vaccination

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

Cytokine Response Following SARS-CoV-2 Antigen Stimulation in Patients with Predominantly Antibody Deficiencies

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