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Br J Haematol ; 2022 Jun 02.
Article in English | MEDLINE | ID: covidwho-1874397


Allogeneic haematopoietic stem cell transplant (HSCT) recipients remain at high risk of adverse outcomes from coronavirus disease 2019 (COVID-19) and emerging variants. The optimal prophylactic vaccine strategy for this cohort is not defined. T cell-mediated immunity is a critical component of graft-versus-tumour effect and in determining vaccine immunogenicity. Using validated anti-spike (S) immunoglobulin G (IgG) and S-specific interferon-gamma enzyme-linked immunospot (IFNγ-ELIspot) assays we analysed response to a two-dose vaccination schedule (either BNT162b2 or ChAdOx1) in 33 HSCT recipients at ≤2 years from transplant, alongside vaccine-matched healthy controls (HCs). After two vaccines, infection-naïve HSCT recipients had a significantly lower rate of seroconversion compared to infection-naïve HCs (25/32 HSCT vs. 39/39 HCs no responders) and had lower S-specific T-cell responses. The HSCT recipients who received BNT162b2 had a higher rate of seroconversion compared to ChAdOx1 (89% vs. 74%) and significantly higher anti-S IgG titres (p = 0.022). S-specific T-cell responses were seen after one vaccine in HCs and HSCT recipients. However, two vaccines enhanced S-specific T-cell responses in HCs but not in the majority of HSCT recipients. These data demonstrate limited immunogenicity of two-dose vaccination strategies in HSCT recipients, bolstering evidence of the need for additional boosters and/or alternative prophylactic measures in this group.

NPJ Vaccines ; 6(1): 74, 2021 May 13.
Article in English | MEDLINE | ID: covidwho-1228259


As SARS-CoV-2 vaccines are deployed worldwide, a comparative evaluation is important to underpin decision-making. We here report a systematic literature review and meta-analysis of Phase I/II/III human trials and non-human primates (NHP) studies, comparing reactogenicity, immunogenicity and efficacy across different vaccine platforms for comparative evaluation (updated to March 22, 2021). Twenty-three NHP and 32 human studies are included. Vaccines result in mostly mild, self-limiting adverse events. Highest spike neutralizing antibody (nAb) responses are identified for the mRNA-1273-SARS-CoV and adjuvanted NVX-CoV2373-SARS-CoV-2 vaccines. ChAdOx-SARS-CoV-2 produces the highest T cell ELISpot responses. Pre-existing nAb against vaccine viral vector are identified following AdH-5-SARS-CoV-2 vaccination, halving immunogenicity. The mRNA vaccines depend on boosting to achieve optimal immunogenicity especially in the elderly. BNT162b2, and mRNA-1273 achieve >94%, rAd26/5 > 91% and ChAdOx-SARS-CoV-2 > 66.7% efficacy. Across different vaccine platforms there are trade-offs between antibody binding, functional nAb titers, T cell frequency, reactogenicity and efficacy. Emergence of variants makes rapid mass rollout of high efficacy vaccines essential to reduce any selective advantage.

Sci Immunol ; 5(54)2020 12 23.
Article in English | MEDLINE | ID: covidwho-999191


Understanding the nature of immunity following mild/asymptomatic infection with SARS-CoV-2 is crucial to controlling the pandemic. We analyzed T cell and neutralizing antibody responses in 136 healthcare workers (HCW) 16-18 weeks after United Kingdom lockdown, 76 of whom had mild/asymptomatic SARS-CoV-2 infection captured by serial sampling. Neutralizing antibodies (nAb) were present in 89% of previously infected HCW. T cell responses tended to be lower following asymptomatic infection than in those reporting case-definition symptoms of COVID-19, while nAb titers were maintained irrespective of symptoms. T cell and antibody responses were sometimes discordant. Eleven percent lacked nAb and had undetectable T cell responses to spike protein but had T cells reactive with other SARS-CoV-2 antigens. Our findings suggest that the majority of individuals with mild or asymptomatic SARS-CoV-2 infection carry nAb complemented by multispecific T cell responses at 16-18 weeks after mild or asymptomatic SARS-CoV-2 infection.

Antibodies, Neutralizing/immunology , Asymptomatic Infections , COVID-19/immunology , T-Lymphocytes/immunology , Antibodies, Neutralizing/blood , Antibodies, Viral/blood , Antibodies, Viral/immunology , Case-Control Studies , Cross-Sectional Studies , Humans , SARS-CoV-2/immunology