Serum Neutralizing Activity of mRNA-1273 Against SARS-CoV-2 Variants

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants has led to growing concerns over increased transmissibility and the ability of some variants to partially escape immunity. Sera from participants immunized on a prime-boost schedule with the mRNA-1273 COVID-19 vaccine were tested for neutralizing activity against several SARS-CoV-2 variants, including variants of concern (VOCs) and variants of interest (VOIs), compared to neutralization of the wild-type SARS-CoV-2 virus (designated as D614G). Results showed minimal, statistically non-significant effects on neutralization titers against the B.1.1.7 (Alpha) variant (1.2-fold reduction compared with D614G); other VOCs such as B.1.351 (Beta, including B.1.351-v1, B.1.351-v2, and B.1.351-v3), P.1 (Gamma), and B.1.617.2 (Delta), showed significantly decreased neutralization titers ranging from 2.1-fold to 8.4-fold reductions compared with D614G, although all remained susceptible to mRNA-1273–elicited serum neutralization. IMPORTANCE In light of multiple variants of SARS-CoV-2 that have been documented globally during the COVID-19 pandemic, it remains important to continually assess the ability of currently available vaccines to confer protection against newly emerging variants. Data presented herein indicate that immunization with the mRNA-1273 COVID-19 vaccine produces neutralizing antibodies against key emerging variants tested, including variants of concern and variants of interest. While the serum neutralization elicited by mRNA-1273 against most variants tested was reduced compared with the wild-type virus, they are still expected to be protective. Such data are crucial to inform ongoing and future vaccination strategies to combat COVID-19.

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Vaccination with SARS-CoV-2 variants of concern protects mice from challenge with wild-type virus

PLoS Biology ◽

10.1371/journal.pbio.3001384 ◽

2021 ◽

Vol 19 (12) ◽

pp. e3001384

Author(s):

Fatima Amanat ◽

Shirin Strohmeier ◽

Philip Meade ◽

Nicholas Dambrauskas ◽

Barbara Mühlemann ◽

...

Keyword(s):

Mouse Model ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Antibody Responses ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Fold Reduction ◽

Reactive Antibody

Vaccines against Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) have been highly efficient in protecting against Coronavirus Disease 2019 (COVID-19). However, the emergence of viral variants that are more transmissible and, in some cases, escape from neutralizing antibody responses has raised concerns. Here, we evaluated recombinant protein spike antigens derived from wild-type SARS-CoV-2 and from variants B.1.1.7, B.1.351, and P.1 for their immunogenicity and protective effect in vivo against challenge with wild-type SARS-CoV-2 in the mouse model. All proteins induced high neutralizing antibodies against the respective viruses but also induced high cross-neutralizing antibody responses. The decline in neutralizing titers between variants was moderate, with B.1.1.7-vaccinated animals having a maximum fold reduction of 4.8 against B.1.351 virus. P.1 induced the most cross-reactive antibody responses but was also the least immunogenic in terms of homologous neutralization titers. However, all antigens protected from challenge with wild-type SARS-CoV-2 in a mouse model.

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Serum Neutralizing Activity of mRNA-1273 against SARS-CoV-2 Variants

10.1101/2021.06.28.449914 ◽

2021 ◽

Author(s):

Angela Choi ◽

Matthew Koch ◽

Kai Wu ◽

Groves Dixon ◽

Judith Oestreicher ◽

...

Keyword(s):

Severe Acute Respiratory Syndrome ◽

Wild Type ◽

Neutralizing Activity ◽

Serum Neutralization ◽

Fold Reduction ◽

Alpha Variant

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Kinetics of Neutralizing Antibodies of COVID-19 Patients Tested Using Clinical D614G, B.1.1.7 and B 1.351 Isolates in Microneutralization Assays

Viruses ◽

10.3390/v13060996 ◽

2021 ◽

Vol 13 (6) ◽

pp. 996

Author(s):

Jenni Virtanen ◽

Ruut Uusitalo ◽

Essi M. Korhonen ◽

Kirsi Aaltonen ◽

Teemu Smura ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Acute Infection ◽

Clinical Isolates ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Kinetics Of

Increasing evidence suggests that some newly emerged SARS-CoV-2 variants of concern (VoCs) resist neutralization by antibodies elicited by the early-pandemic wild-type virus. We applied neutralization tests to paired recoveree sera (n = 38) using clinical isolates representing the first wave (D614G), VoC1, and VoC2 lineages (B.1.1.7 and B 1.351). Neutralizing antibodies inhibited contemporary and VoC1 lineages, whereas inhibition of VoC2 was reduced 8-fold, with 50% of sera failing to show neutralization. These results provide evidence for the increased potential of VoC2 to reinfect previously SARS-CoV-infected individuals. The kinetics of NAbs in different patients showed similar decline against all variants, with generally low initial anti-B.1.351 responses becoming undetectable, but with anti-B.1.1.7 NAbs remaining detectable (>20) for months after acute infection.

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Antibody Escape Kinetics of Equine Infectious Anemia Virus Infection of Horses

Journal of Virology ◽

10.1128/jvi.00137-15 ◽

2015 ◽

Vol 89 (13) ◽

pp. 6945-6951 ◽

Cited By ~ 4

Author(s):

Elissa J. Schwartz ◽

Seema Nanda ◽

Robert H. Mealey

Keyword(s):

Neutralizing Antibodies ◽

Equine Infectious Anemia Virus ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Fitness Costs ◽

Equine Infectious Anemia ◽

Anemia Virus ◽

Kinetics Of ◽

Virus Fitness

Lentivirus escape from neutralizing antibodies (NAbs) is not well understood. In this work, we quantified antibody escape of a lentivirus, using antibody escape data from horses infected with equine infectious anemia virus. We calculated antibody blocking rates of wild-type virus, fitness costs of mutant virus, and growth rates of both viruses. These quantitative kinetic estimates of antibody escape are important for understanding lentiviral control by antibody neutralization and in developing NAb-eliciting vaccine strategies.

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Structural Basis for Accommodation of Emerging B.1.351 and B.1.1.7 Variants by Two Potent SARS-CoV-2 Neutralizing Antibodies

10.1101/2021.02.21.432168 ◽

2021 ◽

Cited By ~ 3

Author(s):

Gabriele Cerutti ◽

Micah Rapp ◽

Yicheng Guo ◽

Fabiana Bahna ◽

Jude Bimela ◽

...

Keyword(s):

Monoclonal Antibody ◽

Neutralizing Antibodies ◽

Neutralizing Antibody ◽

Structural Basis ◽

Wild Type Virus ◽

Receptor Binding Domain ◽

Type Virus ◽

Wild Type ◽

Distinct Mechanism ◽

The Uk

SummaryEmerging SARS-CoV-2 strains, B.1.1.7 and B.1.351, from the UK and South Africa, respectively show decreased neutralization by monoclonal antibodies and convalescent or vaccinee sera raised against the original wild-type virus, and are thus of clinical concern. However, the neutralization potency of two antibodies, 1-57 and 2-7, which target the receptor-binding domain (RBD) of spike, was unaffected by these emerging strains. Here, we report cryo-EM structures of 1-57 and 2-7 in complex with spike, revealing each of these antibodies to utilize a distinct mechanism to bypass or accommodate RBD mutations. Notably, each antibody represented a response with recognition distinct from those of frequent antibody classes. Moreover, many epitope residues recognized by 1-57 and 2-7 were outside hotspots of evolutionary pressure for both ACE2 binding and neutralizing antibody escape. We suggest the therapeutic use of antibodies like 1-57 and 2-7, which target less prevalent epitopes, could ameliorate issues of monoclonal antibody escape.

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Age-Dependent Reduction in Neutralization against Alpha and Beta Variants of BNT162b2 SARS-CoV-2 Vaccine-Induced Immunity

Microbiology Spectrum ◽

10.1128/spectrum.00561-21 ◽

2021 ◽

Author(s):

Hitoshi Kawasuji ◽

Yoshitomo Morinaga ◽

Hideki Tani ◽

Yumiko Saga ◽

Makito Kaneda ◽

...

Keyword(s):

Age Groups ◽

Older Age ◽

Spike Protein ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Neutralizing Activity ◽

Age Dependent ◽

Induced Immunity

Since mRNA vaccines utilize wild-type SARS-CoV-2 spike protein as an antigen, there are potential concerns about acquiring immunity to variants of this virus. The neutralizing activity in BNT162b2-vaccinated individuals was higher against the wild-type virus than against its variants; this effect was more apparent in older age groups.

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Severity of SARS-CoV-2 alpha variant (B.1.1.7) in England

Clinical Infectious Diseases ◽

10.1093/cid/ciab754 ◽

2021 ◽

Author(s):

Daniel J Grint ◽

Kevin Wing ◽

Catherine Houlihan ◽

Hamish P Gibbs ◽

Stephen J W Evans ◽

...

Keyword(s):

Hospital Admission ◽

Proportional Hazards ◽

Cox Proportional Hazards ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Gene Target ◽

Individual Level ◽

Increased Risk ◽

Alpha Variant

Abstract Background The SARS-CoV-2 alpha variant (B.1.1.7) is associated with higher transmissibility than wild type virus, becoming the dominant variant in England by January 2021. We aimed to describe the severity of the alpha variant in terms of the pathway of disease from testing positive to hospital admission and death. Methods With the approval of NHS England, we linked individual-level data from primary care with SARS-CoV-2 community testing, hospital admission, and ONS all-cause death data. We used testing data with S-gene target failure as a proxy for distinguishing alpha and wild-type cases, and stratified Cox proportional hazards regression to compare the relative severity of alpha cases compared to wild type diagnosed from 16th November 2020 to 11th January 2021. Results Using data from 185,234 people who tested positive for SARS-CoV-2 in the community (alpha=93,153; wild-type=92,081), in fully adjusted analysis accounting for individual-level demographics and comorbidities as well as regional variation in infection incidence, we found alpha associated with 73% higher hazards of all-cause death (aHR: 1.73 (95% CI 1.41 - 2.13; P<.0001)) and 62% higher hazards of hospital admission (aHR: 1.62 ((95% CI 1.48 - 1.78; P<.0001), compared to wild-type virus. Among patients already admitted to ICU, the association between alpha and increased all-cause mortality was smaller and the confidence interval included the null (aHR: 1.20 (95% CI 0.74 - 1.95; P=0.45)). Conclusions The SARS-CoV-2 alpha variant is associated with an increased risk of both hospitalisation and mortality than wild-type virus.

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Persistence of neutralizing antibodies a year after SARS-CoV-2 infection

10.1101/2021.07.13.21260426 ◽

2021 ◽

Author(s):

Anu Haveri ◽

Nina Ekström ◽

Anna Solastie ◽

Camilla Virta ◽

Pamela Österlund ◽

...

Keyword(s):

Neutralizing Antibodies ◽

Severe Disease ◽

Severe Infection ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Serum Antibodies ◽

Respiratory Coronavirus ◽

Insight Into

Understanding for how long antibodies persist following Severe acute respiratory coronavirus 2 (SARS-CoV-2) infection provides important insight into estimating the duration of immunity induced by infection. We assessed the persistence of serum antibodies following wild-type SARS-CoV-2 infection six and twelve months after diagnosis in 367 individuals of whom 13% had severe disease requiring hospitalization. We determined the SARS-CoV-2 spike (S-IgG) and nucleoprotein IgG concentrations and the proportion of subjects with neutralizing antibodies (NAb). We also measured the NAb titers among a smaller subset of participants (n=78) against a wild-type virus (B.1) and three variants of concern (VOCs): Alpha (B.1.1.7), Beta (B.1.351) and Delta (B.1.617.2). We found that NAb against the wild-type virus and S-IgG persisted in 89% and 97% of subjects for at least twelve months after infection, respectively. IgG and NAb levels were higher after severe infection. NAb titers were significantly lower against variants compared to the wild-type virus.

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Difference of hemaglutinins between wild-type and vaccine measles virus in Indonesia

Paediatrica Indonesiana ◽

10.14238/pi48.1.2008.42-8 ◽

2008 ◽

Vol 48 (1) ◽

pp. 42

Author(s):

Made Setiawan ◽

Agus Sjahrurachman ◽

Fera Ibrahim ◽

Agus Suwandono

Keyword(s):

Neutralizing Antibodies ◽

Measles Virus ◽

Vaccine Virus ◽

Amino Acid Sequences ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Cell Infection ◽

Aminoacid Sequence ◽

H Protein

Background Hemaglutinin (H) protein of measles virus is veryimportant in the process of host cell infection. H protein is alsoable to induce specific antibodies which can neutralize measlesvirus and block the cell infection.Objective This study aimed to explore the nucleotide and aminoacid sequence differences between wild-type measles virus (G2,G3 and D9) with CAM-70, Schwarz and Edmonston-wt vaccinevirus.Methods The exctration and amplification of the gene wereconducted in the laboratory using biomolecular technology. Thegene and protein analysis were conducted using the bioinformatictechnology.Results The results showed that the differences in nucleotidesequences were highest between wild-type virus and CAM-70vaccine virus (76-77 nucleotides), followed by Schwarz (61-64nucleotides) and Edmonston (60-63 nucleotides). The differencesin amino acid sequences were highest between wild-type virusand CAM-70 (24-29 residues), followed by Schwarz (13-20residues) and Edmonston (12-19 residues).Conclusion The Indonesian wild-type measles virus was geneticallycloser to Schwarz vaccine virus than CAM-70 vaccine virus,hence the neutralizing antibodies generated by Schwarz vaccinewere more specific against Indonesian wild-type virus comparedto CAM-70 vaccine.

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The SARS-CoV-2 Lambda variant and its neutralisation efficiency following vaccination with Comirnaty, Israel, April to June 2021

Eurosurveillance ◽

10.2807/1560-7917.es.2021.26.45.2100974 ◽

2021 ◽

Vol 26 (45) ◽

Author(s):

Neta Zuckerman ◽

Ital Nemet ◽

Limor Kliker ◽

Nofar Atari ◽

Yaniv Lustig ◽

...

Keyword(s):

European Countries ◽

Wild Type Virus ◽

Type Virus ◽

Wild Type ◽

Fold Reduction ◽

Increased Susceptibility

The SARS-CoV-2 Lambda (Pango lineage designation C.37) variant of interest, initially identified in Peru, has spread to additional countries. First detected in Israel in April 2021 following importations from Argentina and several European countries, the Lambda variant infected 18 individuals belonging to two main transmission chains without further spread. Micro-neutralisation assays following Comirnaty (BNT162b2 mRNA, BioNTech-Pfizer) vaccination demonstrated a significant 1.6-fold reduction in neutralising titres compared with the wild type virus, suggesting increased susceptibility of vaccinated individuals to infection.

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