Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains

Faulkner, Nikhil; Ng, Kevin W.; Wu, Mary; Harvey, Ruth; Margaritis, Marios; Paraskevopoulou, Stavroula; Houlihan, Catherine; Hussain, Saira; Greco, Maria; Bolland, William; Warchal, Scott; Heaney, Judith; Rickman, Hannah; Spyer, Moria; Frampton, Daniel; Byott, Matthew; Oliveira, Túlio de; Sigal, Alex; Kjær, Svend; Swanton, Charles; Gandhi, Sonia; Beale, Rupert; Gamblin, Steve; McCauley, John W.; Daniels, Rodney S.; Howell, Michael; Bauer, David L.V.; Nastouli, Eleni; Kassiotis, George

doi:10.7554/elife.69317

Cited by 43 publications

(29 citation statements)

References 30 publications

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“…Cele et al 29 also showed that B.1.351 infection generated better cross-neutralizing activity against earlier viral variants. These findings contrast with Faulkner et al 48 , who observed a large decrease in cross-neutralization of WT virus in B.1.1.7-infected individuals. However, Faulkner et al 48 used sera collected at around 11 days POS and, as discussed above, cross-neutralizing activity probably develops over time.…”

Section: Discussioncontrasting

confidence: 95%

“…To counter such mutations and their attendant antigenic changes, vaccines using the spike proteins from these variants of concern (VOCs) are under investigation 44 – 47 . Whether the variant spike proteins will elicit a robust neutralizing response with superior cross-neutralizing activity against parental strains and newly emerging variants has not been extensively studied 29 , 48 , 49 . Natural infection provides an important opportunity to compare the neutralizing antibody titres and cross-neutralizing activity generated from individuals exposed to different spike variants and will give insights into the antigenic distance between spike variants, thereby informing the design of second-generation vaccine candidates based on VOCs.…”

Section: Mainmentioning

confidence: 99%

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Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

et al. 2021

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COVID-19 vaccine design and vaccination rollout need to take into account a detailed understanding of antibody durability and cross-neutralizing potential against SARS-CoV-2 and emerging variants of concern (VOCs). Analyses of convalescent sera provide unique insights into antibody longevity and cross-neutralizing activity induced by variant spike proteins, which are putative vaccine candidates. Using sera from 38 individuals infected in wave 1, we show that cross-neutralizing activity can be detected up to 305 days pos onset of symptoms, although sera were less potent against B.1.1.7 (Alpha) and B1.351 (Beta). Over time, despite a reduction in overall neutralization activity, differences in sera neutralization potency against SARS-CoV-2 and the Alpha and Beta variants decreased, which suggests that continued antibody maturation improves tolerance to spike mutations. We also compared the cross-neutralizing activity of wave 1 sera with sera from individuals infected with the Alpha, the Beta or the B.1.617.2 (Delta) variants up to 79 days post onset of symptoms. While these sera neutralize the infecting VOC and parental virus to similar levels, cross-neutralization of different SARS-CoV-2 VOC lineages is reduced. These findings will inform the optimization of vaccines to protect against SARS-CoV-2 variants.

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Section: Discussioncontrasting

confidence: 95%

Section: Mainmentioning

confidence: 99%

Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

et al. 2021

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“…However, in recent weeks, there has been a resurgence of SARS-CoV-2 cases in Israel. It is important to understand to what extent this resurgence is due to the high infectiousness of the delta variant(Chakraborty et al, 2021), lower protection of the vaccine against the delta or other variants as compared to the original strain(Faulkner et al, 2021; Martínez-Flores et al, 2021), or decreasing levels of anti-SARS-CoV-2 antibodies against all strains in vaccinated individuals(Israel et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Israel

Shenhar

Green

et al. 2021

Preprint

109

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BackgroundImmune protection following either vaccination or infection with SARS-CoV-2 decreases over time.ObjectiveTo determine the kinetics of SARS-CoV-2 IgG antibodies following administration of two doses of BNT162b2 vaccine, or SARS-CoV-2 infection in unvaccinated individuals.MethodsAntibody titers were measured between January 31, 2021, and July 31, 2021 in two mutually exclusive groups: i) vaccinated individuals who received two doses of BNT162b2 vaccine and had no history of previous infection with COVID-19 and ii) SARS-CoV-2 convalescents who had not received the vaccine.ResultsA total of 2,653 individuals fully vaccinated by two doses of vaccine during the study period and 4,361 convalescent patients were included. Higher SARS-CoV-2 IgG antibody titers were observed in vaccinated individuals (median 1581 AU/mL IQR [533.8-5644.6]) after the second vaccination, than in convalescent individuals (median 355.3 AU/mL IQR [141.2-998.7]; p<0.001). In vaccinated subjects, antibody titers decreased by up to 40% each subsequent month while in convalescents they decreased by less than 5% per month. Six months after BNT162b2 vaccination 16.1% subjects had antibody levels below the seropositivity threshold of <50 AU/mL, while only 10.8% of convalescent patients were below <50 AU/mL threshold after 9 months from SARS-CoV-2 infection.ConclusionsThis study demonstrates individuals who received the Pfizer-BioNTech mRNA vaccine have different kinetics of antibody levels compared to patients who had been infected with the SARS-CoV-2 virus, with higher initial levels but a much faster exponential decrease in the first group.FundingThis research was internally funded by Leumit Health Services (LHS) and was supported in part by the Intramural Research Program, National Institutes of Health, National Cancer Institute, Center for Cancer Research.The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government.Impact statementLarge scale study display the kinetics of SARS-CoV-2 IgG antibodies present in individuals vaccinated with two doses of mRNA vaccine vs. unvaccinated patients who had recovered from the disease: initial levels of antibody are much higher in vaccinated patients, but decrease faster.

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“…To improve vaccine efficacies and boost mucosal immunity against current and future SARS-CoV-2 variants researchers and vaccine companies are already investing the development of second-generation vaccines using diverse strategies. Interestingly, studies have shown that, in contrast to the early Wuhan-1 virus isolate or the Alpha variant, antibodies elicited in response to the Beta variant exhibit potent cross-reactivity as demonstrated by the binding and neutralization of S proteins from the Beta and P.1 variants, which emphasizes use of the Beta variant spike as a seed antigen for the next generation of vaccines [197,198]. Hence, Biontech, CureVac and AstraZeneca have designed a second-generation vaccine based on the Beta-variant S protein mutations.…”

Section: Discussionmentioning

confidence: 99%

Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

et al. 2021

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Since late 2019 the newly emerged pandemic SARS-CoV-2, the causative agent of COVID‑19, has hit the world with recurring waves of infections necessitating the global implementation of non-pharmaceutical interventions, including strict social distancing rules, the wearing of masks and the isolation of infected individuals in order to restrict virus transmissions and prevent the breakdown of our healthcare systems. These measures are not only challenging on an economic level but also have a strong impact on social lifestyles. Using traditional and novel technologies, highly efficient vaccines against SARS-CoV-2 were developed and underwent rapid clinical evaluation and approval to accelerate the immunization of the world population, aiming to end the pandemic and return to normality. However, the emergence of virus variants with improved transmission, enhanced fitness and partial immune escape from the first generation of vaccines poses new challenges, which are currently being addressed by scientists and pharmaceutical companies all over the world. In this ongoing pandemic, the evaluation of SARS-CoV-2 vaccines underlies diverse unpredictable dynamics, posed by the first broad application of the mRNA vaccine technology and their compliance, the occurrence of unexpected side effects and the rapid emergence of variations in the viral antigen. However, despite these hurdles, we conclude that the available SARS-CoV-2 vaccines are very safe and efficiently protect from severe COVID-19 and are thereby the most powerful tools to prevent further harm to our healthcare systems, economics and individual lives. This review summarizes the unprecedented pathways of vaccine development and approval during the ongoing SARS-CoV-2 pandemic. We focus on the real-world effectiveness and unexpected positive and negative side effects of the available vaccines and summarize the timeline of the applied adaptations to the recommended vaccination strategies in the light of emerging virus variants. Finally, we highlight upcoming strategies to improve the next generations of SARS-CoV-2 vaccines.

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Reduced antibody cross-reactivity following infection with B.1.1.7 than with parental SARS-CoV-2 strains

Cited by 43 publications

References 30 publications

Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

Neutralizing antibody activity in convalescent sera from infection in humans with SARS-CoV-2 and variants of concern

Large-scale study of antibody titer decay following BNT162b2 mRNA vaccine or SARS-CoV-2 infection

Shooting at a Moving Target—Effectiveness and Emerging Challenges for SARS-CoV-2 Vaccine Development

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