Community Series in Vaccines and approaches that target trained immunity in COVID-19: Immunological mechanisms of action and delivery: Volume II

Editors

Yongjun Sui

National Cancer Institute (NIH)

Nargis Khan

University of Calgary

Impact

4/5, XBB.1.5, XBB.1.16 and EG.5.1). (B) Neutralization of the mAbs to SARS-CoV-2 pseudoviruses bearing the spike of the indicated VOCs (B1.1.529, wild type SARS-CoV-2). (C) Half-maximal inhibitory concentration (IC50) values of the mAbs to pseudoviruses (wild type, B1.1.529, BA.4/5, XBB.1.5, XBB.1.16 and EG.5.1). (D) The heat map illustrates the OD450 nm values obtained from the competitive ELISA analysis of the monoclonal antibodies (mAbs) for epitope binding. Graphs show mean ± SD, n = 3 technical replicates for (A, B).

Original Research

06 March 2024

Rapid isolation of pan-neutralizing antibodies against Omicron variants from convalescent individuals infected with SARS-CoV-2

Peng Yu

, 6 more and

Tianchen Xiong

Introduction: The emergence of SARS-CoV-2 Omicron subvariants has presented a significant challenge to global health, as these variants show resistance to most antibodies developed early in the pandemic. Therapeutic antibodies with potent efficacy to the Omicron variants are urgently demanded.

Methods: Utilizing the rapid antibody discovery platform, Berkeley Lights Beacon, we isolated two monoclonal neutralizing antibodies, 2173-A6 and 3462-A4. These antibodies were isolated from individuals who recently recovered from Omicron infections.

Results: Both antibodies, 2173-A6 and 3462-A4, demonstrated high affinity for the RBD and effectively neutralized pseudoviruses from various Omicron lineages, including BA.4/5, XBB.1.16, XBB.1.5, and EG.5.1. This neutralization was achieved through binding to identical or overlapping epitopes.

Discussion: The use of the Beacon platform enabled the rapid isolation and identification of effective neutralizing antibodies within less than 10 days. This process significantly accelerates the development of novel therapeutic antibodies, potentially reducing the time required to respond to unknown infectious diseases in the future.

3,964 views

5 citations

Spike proteins were from the SARS-CoV-2 prototype and B. 1. 1. 7, B. 1. 351, B. 1. 526. 1, B. 1. 617, B. 1. 617. 1, B. 1. 617. 2, B. 1. 617. 3, P. 1, P. 2, BA. 2, BA. 2. 12. 1, BA. 2. 75, BA. 2. 12. 1, BA. 2+L452M, BA. 2+L452R, BA. 3, BA. 4, and BA. 5 strains, respectively. Numbers indicate the average values of the corresponding groups (N=5 in each group).

Original Research

30 April 2024

A universal recombinant adenovirus type 5 vector-based COVID-19 vaccine

Xingxing Li

, 7 more and

Yuhua Li

2,155 views

0 citations

Original Research

16 August 2023

Five doses of the mRNA vaccination potentially suppress ancestral-strain stimulated SARS-CoV2-specific cellular immunity: a cohort study from the Fukushima vaccination community survey, Japan

Yuta Tani

, 12 more and

Masaharu Tsubokura

The bivalent mRNA vaccine is recommended to address coronavirus disease variants, with additional doses suggested for high-risk groups. However, the effectiveness, optimal frequency, and number of doses remain uncertain. In this study, we examined the long-term cellular and humoral immune responses following the fifth administration of the mRNA severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in patients undergoing hemodialysis. To our knowledge, this is the first study to monitor long-term data on humoral and cellular immunity dynamics in high-risk populations after five doses of mRNA vaccination, including the bivalent mRNA vaccine. Whereas most patients maintained humoral immunity throughout the observation period, we observed reduced cellular immune reactivity as measured by the ancestral-strain-stimulated ELISpot assay in a subset of patients. Half of the individuals (50%; 14/28) maintained cellular immunity three months after the fifth dose, despite acquiring humoral immunity. The absence of a relationship between positive controls and T-Spot reactivity suggests that these immune alterations were specific to SARS-CoV-2. In multivariable analysis, participants aged ≥70 years showed a marginally significant lower likelihood of having reactive results. Notably, among the 14 individuals who received heterologous vaccines, 13 successfully acquired cellular immunity, supporting the effectiveness of this administration strategy. These findings provide valuable insights for future vaccination strategies in vulnerable populations. However, further research is needed to evaluate the involvement of immune tolerance and exhaustion through repeated vaccination to optimize immunization strategies.

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7 citations

Serum samples were obtained from participants about 18 days after the third injection of the vaccine, and anti-SARS-CoV-2 IgG antibodies were measured using 2019-nCovIgG Chemiluminescent Immunoassay Microparticles (A). Spearman or Pearson correlation analysis was used to assess the correlation between laboratory indicators and neutralizing antibody levels in the PLWH group (B–H). *p<0.05.

Clinical Trial

15 November 2023

A third (booster) dose of the inactivated SARS-CoV-2 vaccine elicits immunogenicity and T follicular helper cell responses in people living with HIV

Zhengchao Lv

, 13 more and

Chunping Wan

1,892 views

3 citations

Original Research

01 August 2023

Homologous versus Heterologous prime-boost COVID-19 Vaccination in autologous hematopoietic stem cell transplantation recipients: a blinded randomized controlled trial

Leyla Sharifi Aliabadi

, 5 more and

Mohammad Vaezi

2,988 views

3 citations

Original Research

26 July 2023

Multi-phasic gene profiling using candidate gene approach predict the capacity of specific antibody production and maintenance following COVID-19 vaccination in Japanese population

Yuki Takemoto

, 6 more and

Hideki Ohdan

2,362 views

4 citations

(B) Ancestral spike primed T cells were expanded for 14 days and challenged with indicated peptide libraries of variants of SCoV2. Each variant library consisted of peptides spanning mutated regions only. Dot-plots shows antigen-specific CD4+ T cell response.

Case Report

03 July 2023

Case Report: Kinetics and durability of humoral and cellular response of SARS-CoV-2 messenger RNA vaccine in a lung and kidney transplant recipient

James Long

, 4 more and

Valeria De Giorgi

2,580 views

1 citations

Original Research

15 March 2023

Humoral and cellular immunity to SARS-COV-2 after vaccination with mRNA vaccines in PLWH with discordant immune response. Influence of the vaccine administered

Luis F. López-Cortés

, 10 more and

Alicia Gutiérrez-Valencia

Background: Data on SARS-CoV-2 mRNA vaccine immunogenicity in people living with human immunodeficiency virus (PLWH) and discordant immune response (DIR) are currently limited. Therefore, we compare the immunogenicity of these vaccines in DIR and immunological responders (IR).

Methods: A prospective cohort that enrolled 89 participants. Finally, 22 IR and 24 DIR were analyzed before vaccination (T₀), one (T₁) and six months (T₂) after receiving BNT162b2 or mRNA-1273 vaccine. Additionally, 10 IR and 16 DIR were evaluated after a third dose (T₃). Anti-S-RBD IgG, neutralizing antibodies (nAb), neutralization activity, and specific memory B cells were quantified. Furthermore, specific CD4⁺ and CD8⁺ responses were determined by intracellular cytokine staining and polyfunctionality indexes (Pindex).

Results: At T₁, all participants developed anti-S-RBD. 100% IR developed nAb compared to 83.3% DIR. Spike-specific B cells were detected in all IR and 21/24 DIR. Memory CD4⁺ T cells responded in 5/9 IR and 7/9 DIR, mainly based on the expression of IFN-γ and TNF-α, with a higher Pindex in DIR. Memory CD8⁺ T cells responded in only four participants in each group. At T₂, anti-S-RBD and nAb titers were higher in DIR than in IR. In both groups, there was an increase in specific B memory cells, higher in DIR. Six IR and five DIR maintained a specific memory CD4⁺ response. Memory CD8⁺ response was preserved in IR but was lost in DIR. In a multivariate linear regression analysis, receiving mRNA-1273 instead of BNT162b2 played a prominent role in the results.

Conclusions: Our data suggest that PLWH with DIR can mount an immune response similar to those with higher CD4⁺, provided they receive the mRNA-1273 vaccine instead of others less immunogenic.

2,923 views

9 citations

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