Durability and breadth of neutralisation following multiple antigen exposures to SARS-CoV-2 infection and/or COVID-19 vaccination

Underwood, Alexander; Sølund, Christina; Fernandez-Antunez, Carlota; Villadsen, Signe Lysemose; Mikkelsen, Lotte S.; Fahnøe, Ulrik; Bollerup, Signe; Winckelmann, Anni; Schneider, Uffe Vest; Binderup, Alekxander; Vizgirda, Greta; Sørensen, Anna-Louise; Vinten, Caroline Nørløv; Dalegaard, Magnus Illum; Ramírez, Santseharay; Weis, Nina; Bukh, Jens

doi:10.1016/j.ebiom.2023.104475

Cited by 11 publications

(13 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another study performed in 30 million peoples showed increased risk of severe COVID-19 outcome 10 weeks after a second shot of the Pfizer and AstraZeneca vaccine 8 . Because of the waning of binding and neutralizing antibody levels, booster doses were introduced to bolster immune defense against SARS-CoV-2 infections 9 , 10 . It is currently unknown what levels of antibody responses are being generated against the COVID-19 vaccines and the duration of these antibodies in the peripheral circulation of the community peoples in Bangladesh.…”

Section: Introductionmentioning

confidence: 99%

Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh

Haq,

Roy,

Ahmed

et al. 2024

Sci Rep

View full text Add to dashboard Cite

COVID-19 vaccines have been effective in preventing severe illness, hospitalization and death, however, the effectiveness diminishes with time. Here, we evaluated the longevity of antibodies generated by COIVD-19 vaccines and the risk of (re)infection in Bangladeshi population. Adults receiving two doses of AstraZeneca, Pfizer, Moderna or Sinopharm vaccines were enrolled at 2–4 weeks after second dosing and followed-up at 4-monthly interval for 1 year. Data on COVID-like symptoms, confirmed COVID-19 infection, co-morbidities, and receipt of booster dose were collected; blood was collected for measuring spike (S)- and nucleocapsid (N)-specific antibodies. S-specific antibody titers reduced by ~ 50% at 1st follow-up visit and continued to decline unless re-stimulated by booster vaccine dose or (re)infection. Individuals infected between follow-up visits showed significantly lower S-antibody titers at preceding visits compared to the uninfected individuals. Pre-enrolment infection between primary vaccination dosing exhibited 60% and 50% protection against reinfection at 5 and 9 months, respectively. mRNA vaccines provided highest odds of protection from (re)infection up to 5 months (Odds Ratio (OR) = 0.08), however, protection persisted for 9 months in AstraZeneca vaccine recipients (OR = 0.06). In conclusion, vaccine-mediated protection from (re)infection is partially linked to elevated levels of S-specific antibodies. AstraZeneca vaccine provided the longest protection.

show abstract

Section: Introductionmentioning

confidence: 99%

Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh

Haq,

Roy,

Ahmed

et al. 2024

Sci Rep

View full text Add to dashboard Cite

show abstract

“…So far, the breadth of SARS-CoV-2 therapeutics has been assessed through the use of past variants and observed mutations 20,60–62 . Measuring breadth in this way does not adequately predict long-term resistance against future variants.…”

Section: Discussionmentioning

confidence: 99%

Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants

Frei,

Gao,

Han

et al. 2023

Preprint

View full text Add to dashboard Cite

Most COVID-19 antibody therapies rely on binding the SARS-CoV-2 receptor binding domain (RBD). However, heavily mutated variants such as Omicron and its sublineages, which are characterized by an ever increasing number of mutations in the RBD, have rendered prior antibody therapies ineffective, leaving no clinically approved antibody treatments for SARS-CoV-2. Therefore, the capacity of therapeutic antibody candidates to bind and neutralize current and prospective SARS-CoV-2 variants is a critical factor for drug development. Here, we present a deep learning-guided approach to identify antibodies with enhanced resistance to SARS-CoV-2 evolution. We apply deep mutational learning (DML), a machine learning-guided protein engineering method to interrogate a massive sequence space of combinatorial RBD mutations and predict their impact on angiotensin-converting enzyme 2 (ACE2) binding and antibody escape. A high mutational distance library was constructed based on the full-length RBD of Omicron BA.1, which was experimentally screened for binding to the ACE2 receptor or neutralizing antibodies, followed by deep sequencing. The resulting data was used to train ensemble deep learning models that could accurately predict binding or escape for a panel of therapeutic antibody candidates targeting diverse RBD epitopes. Furthermore, antibody breadth was assessed by predicting binding or escape to synthetic lineages that represent millions of sequences generated usingin silicoevolution, revealing combinations with complementary and enhanced resistance to viral evolution. This deep learning approach may enable the design of next-generation antibody therapies that remain effective against future SARS-CoV-2 variants.

show abstract

“…As reported previously ( 19 ), to determine if a participant had been infected, plasma was screened longitudinally for the presence of anti-nucleocapsid (N) antibodies using a EuroImmun semi-quantitative enzyme-linked immunosorbent assay (ELISA) (PerkinElmer, cat#: EI 2606-9601-2 G). All time points were compared to the pre-vaccination time point and a signal/noise ratio of 3.0 or more was considered positive.…”

Section: Methodsmentioning

confidence: 99%

“…Initially, all participants included in this study were screened for plasma neutralization using a D614G SARS-CoV-2 isolate (DK-AHH1, Genbank accession number MZ049597), as described previously ( 19 , 20 , 22 ). In brief, virus was added to 2-fold serially diluted plasma at a 1:1 ratio and incubated at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Neutralizing antibody and CD8+ T cell responses following BA.4/5 bivalent COVID-19 booster vaccination in adults with and without prior exposure to SARS-CoV-2

Underwood,

Sølund,

Jacobsen

et al. 2024

Front. Immunol.

Self Cite

View full text Add to dashboard Cite

As severe acute respiratory coronavirus 2 (SARS-CoV-2) variants continue to emerge, it is important to characterize immune responses against variants which can inform on protection efficacies following booster vaccination. In this study, neutralizing breadth and antigen-specific CD8+ T cell responses were analyzed in both infection-naïve and infection-experienced individuals following administration of a booster bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine. Significantly higher neutralizing titers were found after this vaccination compared to the pre-third booster vaccination time point. Further, neutralizing breadth to omicron variants, including BA.1, BA.2, BA.5, BQ.1 and XBB.1, was found to be boosted following bivalent vaccination. SARS-CoV-2-specific CD8+ T cells were identified, but with no evidence that frequencies were increased following booster vaccinations. Spike protein-specific CD8+ T cells were the only responses detected after vaccination and non-spike-specific CD8+ T cells were only detected after infection. Both spike-specific and non-spike-specific CD8+ T cells were found at much lower frequencies than CD8+ T cells specific to cytomegalovirus (CMV), Epstein-Barr virus (EBV) and influenza (Flu). Taken together, these results show that the bivalent Wuhan-Hu-1+BA.4/5 Comirnaty® mRNA vaccine boosted the breadth of neutralization to newer SARS-CoV-2 variants and that vaccination is able to induce spike protein-specific CD8+ T cell responses, which are maintained longitudinally.

show abstract

Durability and breadth of neutralisation following multiple antigen exposures to SARS-CoV-2 infection and/or COVID-19 vaccination

Cited by 11 publications

References 50 publications

Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh

Antibody longevity and waning following COVID-19 vaccination in a 1-year longitudinal cohort in Bangladesh

Deep learning-guided selection of antibody therapies with enhanced resistance to current and prospective SARS-CoV-2 Omicron variants

Neutralizing antibody and CD8+ T cell responses following BA.4/5 bivalent COVID-19 booster vaccination in adults with and without prior exposure to SARS-CoV-2

Contact Info

Product

Resources

About