scholarly journals Antibody Response and Variant Cross-Neutralization After SARS-CoV-2 Breakthrough Infection

JAMA ◽  
2021 ◽  
Author(s):  
Timothy A. Bates ◽  
Savannah K. McBride ◽  
Bradie Winders ◽  
Devin Schoen ◽  
Lydie Trautmann ◽  
...  
2021 ◽  
Author(s):  
Shuchi Anand ◽  
Maria E Montez-Rath ◽  
Jialin Han ◽  
Pablo Garcia ◽  
LinaCel Cadden ◽  
...  

Background: Patients receiving dialysis are a sentinel population for groups at high risk for death and disability from COVID-19. Understanding correlates of protection post-vaccination can inform immunization and mitigation strategies. Methods: Monthly since January 2021, we tested plasma from 4791 patients receiving dialysis for antibodies to the receptor-binding domain (RBD) of SARS-CoV-2 using a high-throughput assay. We qualitatively assessed the proportion without a detectable RBD response and among those with a response, semiquantitative median IgG index values. Using a nested case-control design, we matched each breakthrough case to five controls by age, sex, and vaccination-month to determine whether peak and pre-breakthrough RBD IgG index values were associated with risk for infection post-vaccination. Results: Among 2563 vaccinated patients, the proportion without a detectable RBD response increased from 6.6% [95% CI 5.5-8.1] in 14-30 days post-vaccination to 20.2% [95% CI 17.1-23.8], and median index values declined from 92.7 (95% CI 77.8-107.5) to 3.7 (95% CI 3.1-4.3) after 5 months. Persons with SARS-CoV-2 infection prior-to-vaccination had higher peak index values than persons without prior infection, but values equalized by 5 months (p=0.230). Breakthrough infections occurred in 56 patients, with samples collected a median of 21 days pre-breakthrough. Peak and pre-breakthrough RBD values <23 (equivalent to <506 WHO BAU/mL) were associated with higher odds for breakthrough infection (OR: 3.7 [95% CI 2.0-6.8] and 9.8 [95% CI 2.9-32.8], respectively). Conclusions: The antibody response to SARS-CoV-2 vaccination wanes rapidly, and in persons receiving dialysis, the persisting antibody response is associated with risk for breakthrough infection.


2021 ◽  
Author(s):  
Liane Dupont ◽  
Luke B Snell ◽  
Carl Graham ◽  
Jeffrey Seow ◽  
Blair Merrick ◽  
...  

As SARS–CoV–2 variants continue to emerge globally, a major challenge for COVID–19 vaccination is the generation of a durable antibody response with cross–neutralizing activity against both current and newly emerging viral variants. Cross–neutralizing activity against major variants of concern (B.1.1.7, P.1 and B.1.351) has been observed following vaccination, albeit at a reduced potency, but whether vaccines based on the Spike glycoprotein of these viral variants will produce a superior cross–neutralizing antibody response has not been fully investigated. Here, we used sera from individuals infected in wave 1 in the UK to study the long-term cross-neutralization up to 10 months post onset of symptoms (POS), as well as sera from individuals infected with the B.1.1.7 variant to compare cross–neutralizing activity profiles. We show that neutralizing antibodies with cross-neutralizing activity can be detected from wave 1 up to 10 months POS. Although neutralization of B.1.1.7 and B.1.351 is lower, the difference in neutralization potency decreases at later timepoints suggesting continued antibody maturation and improved tolerance to Spike mutations. Interestingly, we found that B.1.1.7 infection also generates a cross-neutralizing antibody response, which, although still less potent against B.1.351, can neutralize parental wave 1 virus to a similar degree as B.1.1.7. These findings have implications for the optimization of vaccines that protect against newly emerging viral variants.


2021 ◽  
Author(s):  
S Momsen Reincke ◽  
Meng Yuan ◽  
Hans-Christian Kornau ◽  
Victor M Corman ◽  
Scott van Hoof ◽  
...  

SARS-CoV-2 Beta variant of concern (VOC) resists neutralization by major classes of antibodies from non-VOC COVID-19 patients and vaccinated individuals. Here, serum of Beta variant infected patients revealed reduced cross-neutralization of non-VOC virus. From these patients, we isolated Beta-specific and cross-reactive receptor-binding domain (RBD) antibodies. The Beta-specificity results from recruitment of novel VOC-specific clonotypes and accommodation of VOC-defining amino acids into a major non-VOC antibody class that is normally sensitive to these mutations. The Beta-elicited cross-reactive antibodies share genetic and structural features with non-VOC-elicited antibodies, including a public VH1-58 clonotype targeting the RBD ridge independent of VOC mutations. These findings advance our understanding of the antibody response to SARS-CoV-2 shaped by antigenic drift with implications for design of next-generation vaccines and therapeutics.


Author(s):  
Huibin Lv ◽  
Nicholas C. Wu ◽  
Owen Tak-Yin Tsang ◽  
Meng Yuan ◽  
Ranawaka A. P. M. Perera ◽  
...  

AbstractThe World Health Organization has recently declared the ongoing outbreak of COVID-19, which is caused by a novel coronavirus SARS-CoV-2, as pandemic. There is currently a lack of knowledge in the antibody response elicited from SARS-CoV-2 infection. One major immunological question is concerning the antigenic differences between SARS-CoV-2 and SARS-CoV. We address this question by using plasma from patients infected by SARS-CoV-2 or SARS-CoV, and plasma obtained from infected or immunized mice. Our results show that while cross-reactivity in antibody binding to the spike protein is common, cross-neutralization of the live viruses is rare, indicating the presence of non-neutralizing antibody response to conserved epitopes in the spike. Whether these non-neutralizing antibody responses will lead to antibody-dependent disease enhancement needs to be addressed in the future. Overall, this study not only addresses a fundamental question regarding the antigenicity differences between SARS-CoV-2 and SARS-CoV, but also has important implications in vaccine development.


2022 ◽  
Author(s):  
Sho Miyamoto ◽  
Takeshi Arashiro ◽  
Yu Adachi ◽  
Saya Moriyama ◽  
Hitomi Kinoshita ◽  
...  

Background The immune profile against SARS-CoV-2 has dramatically diversified due to a complex combination of exposure to vaccines and infection by various lineages/variants, likely generating a heterogeneity in protective immunity in a given population. To further complicate this, the Omicron variant, with numerous spike mutations, has emerged. These circumstances have created the need to assess the potential of immune evasion by the Omicron in individuals with various immune histories. Methods The neutralization susceptibility of the variants including the Omicron and their ancestor was comparably assessed using a panel of plasma/serum derived from individuals with divergent immune histories. Blood samples were collected from either mRNA vaccinees or from those who suffered from breakthrough infections by the Alpha/Delta with multiple time intervals following vaccination. Findings The Omicron was highly resistant to neutralization in fully vaccinated individuals without a history of breakthrough infections. In contrast, robust cross-neutralization against the Omicron were induced in vaccinees that experienced breakthrough infections. The time interval between vaccination and infection, rather than the variant types of infection, was significantly correlated with the magnitude and potency of Omicron-neutralizing antibodies. Conclusions Immune histories with breakthrough infections can overcome the resistance to infection by the Omicron, with the vaccination-infection interval being the key determinant of the magnitude and breadth of neutralization. The diverse exposure history in each individual warrants a tailored and cautious approach to understanding population immunity against the Omicron and future variants. Funding This study was supported by grants from the Japan Agency for Medical Research and Development (AMED).


2021 ◽  
Author(s):  
Shuchi Anand ◽  
Maria E. Montez-Rath ◽  
Jialin Han ◽  
Pablo Garcia ◽  
LinaCel Cadden ◽  
...  

2021 ◽  
Author(s):  
Yosuke Hirotsu ◽  
Toshiharu Tsutsui ◽  
Yumiko Kakizaki ◽  
Yoshihiro Miyashita ◽  
Fumiaki Iwase ◽  
...  

Abstract Vaccination is expected to suppress COVID-19 infection. However, breakthrough infections have increased following vaccination because of the spread of variants of concern, notably Delta (B.1.617.2 lineage). Virological and serological data pertaining to post-vaccination infections are limited. Here, we conducted genome analysis determined the viral lineages that infected patients following vaccination. Changes in viral load, antibody levels, and viral antigen levels following infection were analyzed. At the time of infection, Delta-infected patients had a 6.2-fold and 12.3-fold higher viral load compared with Alpha and other lineages, respectively. Viral lineages (Delta:Alpha:Other) of infection were 0:12:0 in the fully vaccinated group, 1:11:0 in the partially vaccinated group, 9:16:0 in the shortly after vaccination group, and 254:229:165 in the unvaccinated group. Breakthrough infections occurred regardless of retention of high antibody titers following vaccination. At the time of diagnosis, Delta-infected patients showed high viral load with or without vaccination. However, no fully vaccinated patients developed severe disease, and the rapid increase in anti-spike antibodies occurred approximately 1 week after onset of symptoms. Concomitantly, a decrease in viral antigen levels was observed in fully vaccinated patients, shortening the time to negative result by approximately 2 days compared with unvaccinated patients. Collectively, even if breakthrough infection occurs, the rapid antibody response in fully vaccinated individuals contributes to prevention of severe disease, possibly because of suppression of viral replication.


2002 ◽  
Vol 21 (4) ◽  
pp. 337-342 ◽  
Author(s):  
SHU LI ◽  
AN S. F. CHAN ◽  
HOLLY MATTHEWS ◽  
JOSEPH F. HEYSE ◽  
CHRISTINA Y. CHAN ◽  
...  

Retrovirology ◽  
2009 ◽  
Vol 6 (S3) ◽  
Author(s):  
E Gray ◽  
P Moore ◽  
N Ranchobe ◽  
M Abrahams ◽  
M Madiga ◽  
...  

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