Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer

Fendler, Annika; Shepherd, Scott T.C.; Au, Lewis; Wu, Mary; Harvey, Ruth; Schmitt, Andreas M.; Tippu, Zayd; Shum, Benjamin; Farag, Sheima; Rogiers, Aljosja; Carlyle, Eleanor; Edmonds, Kim; Rosario, Lyra Del; Lingard, Karla; Mangwende, Mary; Holt, Lucy; Ahmod, Hamid; Korteweg, Justine; Foley, Tara; Barber, Taja; Emslie-Henry, Andrea; Caulfield-Lynch, Niamh; Byrne, Fiona; Deng, Daqi; Kjær, Svend; Song, Ok‐Ryul; Queval, Christophe J.; Kavanagh, Caitlin; Wall, Emma C; Carr, Edward J; Caidan, Simon; Gavrielides, Mike; MacRae, James I.; Kelly, Gavin; Peat, Kema; Kelly, Denise; Murra, Aida; Kelly, Kayleigh; O’Flaherty, Molly; Shea, Robyn; Gardner, Gail; Murray, Darren R.; Yousaf, Nadia; Jhanji, Shaman; Tatham, Kate; Cunningham, David; As, Nicholas van; Young, Kate; Furness, Andrew J.S.; Pickering, Lisa; Beale, Rupert; Swanton, Charles; Gandhi, Sonia; Gamblin, Steve; Bauer, David L.V.; Kassiotis, George; Howell, Michael; Nicholson, Emma; Walker, Susanna; Larkin, James; Turajlic, Samra

doi:10.1016/s0140-6736(22)00147-7

Cited by 71 publications

(101 citation statements)

References 15 publications

(24 reference statements)

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“…However, as previously reported in healthy individuals and solid tumor patients (2-4, 11, 12, 15-17), in this study neutralizing antibody levels against Omicron were reduced in comparison with the ancestral virus. Altogether, our results build on previous findings showing that B cell-targeted therapies are associated with reduced antibody responses after primary vaccination (20, 22-24, 28, 29) and that a significant fraction of patients with B cell malignancies remain seronegative after booster immunization (12,17,23,25,30). Our findings contrast with the studies in solid tumor patients, where the majority of patients develop robust booster-mediated responses, although cytoreductive chemotherapies may impair responses in select patients (11,18,(20)(21)(22)31).…”

Section: Discussionsupporting

confidence: 84%

Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses

Azar

Evans

Sikorski

et al. 2022

Preprint

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The impact of SARS-CoV2 vaccination in cancer patients remains incompletely understood given the heterogeneity of cancer and cancer therapies. We assessed vaccine-induced antibody response to the SARS-CoV2 Omicron (B.1.1.529) variant in 57 patients with B cell malignancies with and without active B cell-targeted therapy. Ancestral- and Omicron- reactive antibody levels were determined by ELISA and neutralization assays. In over one third of vaccinated patients at the pre-booster timepoint, there were no ELISA-detectable antibodies against either the ancestral strain or Omicron variant. The lack of vaccine-induced antibodies was predominantly in patients receiving active therapy such as anti-CD20 monoclonal antibody (mAb) or Bruton's tyrosine kinase inhibitors (BTKi). While booster immunization was able to induce detectable antibodies in a small fraction of seronegative patients, the benefit was disproportionately evident in patients not on active therapy. Importantly, in patients with post-booster ELISA-detectable antibodies, there was a positive correlation of antibody levels against the ancestral strain and Omicron variant. Booster immunization increased overall antibody levels, including neutralizing antibody titers against the ancestral strain and Omicron variant; however, predominantly in patients without active therapy. Furthermore, ancestral strain neutralizing antibody titers were about 5-fold higher in comparison with those to Omicron, suggesting that even with booster administration, there may be reduced protection against the Omicron variant. Interestingly, in almost all patients regardless of active therapy, including those unable to generate detectable antibodies against SARS-CoV2 spike, we observed comparable levels of EBV, influenza, and common cold coronavirus reactive antibodies demonstrating that B cell-targeting therapies primarily impair de novo but not pre-existing antibody levels. These findings suggest that patients with B cell malignancies on active therapy may be at disproportionately higher risk to new versus endemic viral infection and suggest utility for vaccination prior to B cell-targeted therapy.

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Section: Discussionsupporting

confidence: 84%

Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses

Azar

Evans

Sikorski

et al. 2022

Preprint

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“…3). The stringent hamster model is generally well suited to assess both aspects of preclinical VE, individual protection and transmission (24)(25)(26)48). An obvious shortcoming of our current study is the limited infectivity of VOC Omicron in hamsters (30), and that VE of YF-S0*against Omicron can hence not directly be assessed in this gold standard model.…”

Section: Discussionmentioning

confidence: 99%

“…While the intrinsic pathogenic potential of Omicron remains uncertain (21), its antigenic divergence leads to a loss of activity of most therapeutic monoclonal antibodies (22) and failure of current first-generation vaccines to protect from infection (23,24). The maintenance of some cross-protective nAb levels may require repeated booster dosing (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Updated vaccine protects from infection with SARS-CoV-2 variants, prevents transmission and is immunogenic against Omicron in hamsters

Sharma

Vercruysse

Sánchez-Felipe

et al. 2021

Preprint

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All currently used first-generation COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, it remains unclear to which extent vaccination protects against variants of concern (VOC) which fuel the ongoing pandemic. Here we show in a stringent hamster challenge model that immunization using prototypic spike expressed form a potent YF17D viral vector (Sanchez-Felipe et al. 2021) provides vigorous protection against infection with ancestral virus and VOC Alpha (B.1.1.7), however, is insufficient to provide optimal protection against the Beta (B.1.351) variant. To improve vaccine efficacy, a revised vaccine candidate was created that carries a modified spike antigen designed to cover the entire VOC spectrum. Vaccination of hamsters with this updated vaccine candidate provides full protection against intranasal challenge with all four VOC Alpha, Beta, Gamma (P.1) and Delta (B.1.617.2) resulting in complete elimination of infectious virus from the lungs and a marked improvement in lung pathology. Vaccinated hamsters did also no longer transmit the Delta variant to non-vaccinated sentinels. Overall, our data indicate that current first-generation COVID-19 vaccines need to be urgently updated to cover emerging sequence diversity of VOCs to maintain vaccine efficacy and to impede virus spread at the community level.

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“…13 Omicron partially evades antibodies induced by infection or vaccination and it raises concerns regarding the effectiveness of current vaccines. [14][15][16] Few data are available on the response after full vaccination and booster dose in cancer patients 17 and any detailed studies are available in patients with MM and monoclonal gammopathies.…”

Section: Introductionmentioning

confidence: 99%

Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma

Storti

Marchica

Vescovini

et al. 2022

Preprint

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Multiple myeloma (MM) patients may have a reduced response to vaccination due to immunodeficiency. The humoral and cellular response to SARS-CoV-2 mRNA full vaccination and booster dose as well as the impact of spike variants, including the emerging Omicron one, are still unclear and have been investigated in this study in a cohort of MM patients and those with pre-malignant monoclonal gammopathies. Firstly, we have shown that MM patients with relapsed-refractory disease (MMR) had a reduced spike-specific antibody levels and neutralizing titers after SARS-CoV-2 mRNA full vaccination. Interestingly, all the analyzed variants, remarkably Omicron, had a significant negative impact on the neutralizing ability of the vaccine-induced antibodies in all patients with MM and in smoldering MM too. Moreover, lower spike-specific IL-2-producing CD4+ T cells and reduced cytotoxic spike-specific IFN-γ and TNF-α-producing-CD8+ T cells were found in MM patients as compared to MGUS. Finally, we found that booster immunization improved SARS-CoV-2 spike humoral and cellular responses in newly diagnosed MM (MMD) patients and in most, but not all, MMR patients. After the booster dose, a significant increase of the neutralizing antibody titers against almost all the analyzed variants was achieved in MMD. On the other hand, in MMR patients, Omicron retain a negative impact on neutralizing ability, suggesting these patients need to be considered still at risk of Omicron SARS-CoV-2 infection with a clinically relevant disease.

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Omicron neutralising antibodies after third COVID-19 vaccine dose in patients with cancer

Cited by 71 publications

References 15 publications

Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses

Suppression of de novo antibody responses against SARS-CoV2 and the Omicron variant after mRNA vaccination and booster in patients with B cell malignancies undergoing active treatment, but maintenance of pre-existing antibody levels against endemic viruses

Updated vaccine protects from infection with SARS-CoV-2 variants, prevents transmission and is immunogenic against Omicron in hamsters

Impact of Omicron variant on the response to SARS-CoV-2 mRNA Vaccination in multiple myeloma

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