scholarly journals Neutralizing antibody titres to SARS-CoV-2 Omicron variant and wild-type virus in those with past infection or vaccinated or boosted with mRNA BNT162b2 or inactivated CoronaVac vaccines

2022 ◽  
Author(s):  
Malik Peiris ◽  
Samuel Cheng ◽  
Chris Ka Pun Mok ◽  
Yonna Leung ◽  
Susanna Ng ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Wild Type Virus ◽  
Wild Type ◽  
Past Infection ◽  
Post Vaccination ◽  
Antibody Titres ◽  
Duration Of Protection ◽  
Antibody Levels

Abstract Omicron, a novel SARS-CoV-2 variant has emerged and is rapidly becoming the dominant SARS-CoV-2 virus circulating globally. It is important to define reductions in virus neutralizing activity in serum of convalescent or vaccinated individuals to understand potential loss of protection from infection or re-infection. Two doses of BNT162b2 or CoronaVac vaccines provided little 50% plaque reduction neutralization test (PRNT50) antibody immunity against the Omicron variant, even at one-month post vaccination. Booster doses with BNT162b2 in those with two doses of either BNT162b2 or CoronaVac provided acceptable neutralizing immunity against Omicron variant at 1-month post-booster dose. However, three doses of BNT162b2 elicited higher levels of PRNT50 antibody to Omicron variant suggesting longer duration of protection. Convalescent from SARS-CoV-2 infection did not have protective PRNT50 antibody levels to Omicron, but a single dose of BNT162b2 vaccine provided protective immunity. Field vaccine-efficacy studies against Omicron variant against different vaccines are urgently needed.

scholarly journals Herpes Simplex Virus Type 1 Serum Neutralizing Antibody Titers Increase during Latency in Rabbits Latently Infected with Latency-Associated Transcript (LAT)-Positive but Not LAT-Negative Viruses

1999 ◽  
Vol 73 (11) ◽  
pp. 9669-9672 ◽  
Author(s):  
Guey-Chuen Perng ◽  
Susan M. Slanina ◽  
Ada Yukht ◽  
Homayon Ghiasi ◽  
Anthony B. Nesburn ◽  
...  
Keyword(s):  
Neutralizing Antibody ◽  
Wild Type Virus ◽  
Wild Type ◽  
Latently Infected ◽  
Antibody Titers ◽  
Simplex Virus ◽  
Antibody Levels ◽  
Spontaneous Reactivation ◽  
Hsv 1

ABSTRACT The herpes simplex virus type 1 (HSV-1) latency-associated transcript (LAT) gene is essential for efficient spontaneous reactivation in the rabbit ocular model of HSV-1 latency and reactivation. LAT is also the only viral gene abundantly expressed during latency. Rabbits were ocularly infected with the wild-type HSV-1 strain McKrae or the McKrae-derived LAT null mutantdLAT2903. Serum neutralizing antibody titers were determined at various times during acute and latent infection. The neutralizing antibody titers induced by both viruses increased and were similar throughout the first 45 days after infection (P > 0.05). However, by day 59 postinfection (approximately 31 to 45 days after latency had been established), the neutralizing antibody titers induced by wild-type virus anddLAT2903 diverged significantly (P = 0.0005). The dLAT2903-induced neutralizing antibody titers decreased, while the wild-type virus-induced neutralizing antibody titers continued to increase. A rescuant of dLAT2903, in which spontaneous reactivation was fully restored, induced wild-type neutralizing antibody levels on day 59 postinfection. A second LAT mutant with impaired spontaneous reactivation had neutralizing antibody levels comparable to those of dLAT2903. In contrast to the results obtained in rabbits, in mice, neutralizing antibody titers did not increase over time during latency with any of the viruses. Since LAT is expressed in both rabbits and mice during latency, the difference in neutralizing antibody titers between these animals is unlikely to be due to expression of a LAT protein during latency. In contrast, LAT-positive (LAT+), but not LAT-negative (LAT−), viruses undergo efficient spontaneous reactivation in rabbits, while neither LAT+ nor LAT−viruses undergo efficient spontaneous reactivation in mice. Thus, the increase in neutralizing antibody titers in rabbits latently infected with LAT+ viruses may have been due to continued restimulation of the immune system by spontaneously reactivating virus.

scholarly journals A nanoluciferase SARS-CoV-2 for rapid neutralization testing and screening of anti-infective drugs for COVID-19

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xuping Xie ◽  
Antonio E. Muruato ◽  
Xianwen Zhang ◽  
Kumari G. Lokugamage ◽  
Camila R. Fontes-Garfias ◽  
...  
Keyword(s):  
High Throughput ◽  
Neutralization Test ◽  
A549 Cells ◽  
Neutralizing Antibody ◽  
Wild Type Virus ◽  
Antibody Activity ◽  
Type Virus ◽  
Serological Testing ◽  
Wild Type ◽  
Tenofovir Alafenamide

Abstract A high-throughput platform would greatly facilitate coronavirus disease 2019 (COVID-19) serological testing and antiviral screening. Here we present a high-throughput nanoluciferase severe respiratory syndrome coronavirus 2 (SARS-CoV-2-Nluc) that is genetically stable and replicates similarly to the wild-type virus in cell culture. SARS-CoV-2-Nluc can be used to measure neutralizing antibody activity in patient sera within 5 hours, and it produces results in concordance with a plaque reduction neutralization test (PRNT). Additionally, using SARS-CoV-2-Nluc infection of A549 cells expressing human ACE2 receptor (A549-hACE2), we show that the assay can be used for antiviral screening. Using the optimized SARS-CoV-2-Nluc assay, we evaluate a panel of antivirals and other anti-infective drugs, and we identify nelfinavir, rupintrivir, and cobicistat as the most selective inhibitors of SARS-CoV-2-Nluc (EC50 0.77 to 2.74 µM). In contrast, most of the clinically approved antivirals, including tenofovir alafenamide, emtricitabine, sofosbuvir, ledipasvir, and velpatasvir were inactive at concentrations up to 10 µM. Collectively, this high-throughput platform represents a reliable tool for rapid neutralization testing and antiviral screening for SARS-CoV-2.

Persistence of measles neutralizing antibody related to vaccine and natural infection acquired before HIV infection

2013 ◽  
Vol 142 (8) ◽  
pp. 1708-1712 ◽  
Author(s):  
M. B. ISA ◽  
J. V. PAVAN ◽  
P. SICILIA DON ◽  
S. GRUTADAURIA ◽  
L. C. MARTINEZ ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Protective Immunity ◽  
Measles Virus ◽  
Natural Infection ◽  
Geometric Mean ◽  
Neutralizing Antibody ◽  
Wild Type Virus ◽  
Wild Type ◽  
The Status ◽  
Induced Immunity

SUMMARYLittle is known about long-lasting measles protective immunity when exposure to wild-type or vaccine measles virus precedes HIV infection. The results obtained suggest that measles immunity wanes and the lowest measles geometric mean titres (GMT) were significantly associated with measles vaccine-induced immunity in individuals that later developed HIV infection (86% prevalence, GMT 164 mIU/ml) compared to naturally induced immunity in HIV-infected adults (100% prevalence, GMT 340 mIU/ml, P = 0·0082) or non-HIV infected adults (100%, GMT 724 mIU/ml, P = 0·0001), and vaccine-induced immunity in non-HIV-infected adults (100%, GMT 347 mIU/ml, P = 0·017). The study was conducted in an area without wild-type virus circulation since 2000. The absence of virus circulating may alter the paradigm of lifelong immunity to measles virus after vaccination. As the proportion of HIV-infected individuals possessing only vaccine-induced immunity continues to grow, checking the status of measles immunity in this group is strongly recommended.

scholarly journals Growth, Antigenicity, and Immunogenicity of SARS-CoV-2 Spike Variants Revealed by a Live rVSV-SARS-CoV-2 Virus

2022 ◽  
Vol 8 ◽  
Author(s):  
Limin S. Ding ◽  
Yuhang Zhang ◽  
Dan Wen ◽  
Jianbo Ma ◽  
Hao Yuan ◽  
...  
Keyword(s):  
Rna Virus ◽  
Growth Curves ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Wild Type Virus ◽  
Wild Type ◽  
Recurrent Mutations ◽  
Antibody Levels ◽  
Similar Growth

SARS-CoV-2 is an emerging coronavirus threatening human health and the economy worldwide. As an RNA virus, variants emerge during the pandemic and potentially influence the efficacy of the anti-viral drugs and vaccines. Eight spike variants harboring highly recurrent mutations were selected and introduced into a replication-competent recombinant VSV in place of the original G protein (rVSV-SARS-CoV-2). The resulting mutant viruses displayed similar growth curves in vitro as the wild-type virus and could be neutralized by sera from convalescent COVID-19 patients. Several variants, especially Beta strain, showed resistance to human neutralizing monoclonal antibodies targeting the receptor-binding domain (RBD). A single dose of rVSV-SARS-CoV-2 Beta variant could elicit enhanced and broad-spectrum neutralizing antibody responses in human ACE2 knock-in mice and golden Syrian hamsters, while other mutants generated antibody levels comparable to the wild-type. Therefore, our results will be of value to the development of next-generation vaccines and therapeutic antibodies.

scholarly journals Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission

2015 ◽  
Vol 90 (3) ◽  
pp. 1169-1177 ◽  
Author(s):  
Jason Porta ◽  
Vidya Mangala Prasad ◽  
Cheng-I Wang ◽  
Wataru Akahata ◽  
Lisa F. P. Ng ◽  
...  
Keyword(s):  
Chikungunya Virus ◽  
Neutralizing Antibody ◽  
Mutant Virus ◽  
Wild Type Virus ◽  
Type Virus ◽  
Wild Type ◽  
Virus Like Particles ◽  
Fab Fragments ◽  
Cell Transmission ◽  
Viral Surface

ABSTRACTChikungunya virus is a positive-stranded RNA alphavirus. Structures of chikungunya virus-like particles in complex with strongly neutralizing antibody Fab fragments (8B10 and 5F10) were determined using cryo-electron microscopy and X-ray crystallography. By fitting the crystallographically determined structures of these Fab fragments into the cryo-electron density maps, we show that Fab fragments of antibody 8B10 extend radially from the viral surface and block receptor binding on the E2 glycoprotein. In contrast, Fab fragments of antibody 5F10 bind the tip of the E2 B domain and lie tangentially on the viral surface. Fab 5F10 fixes the B domain rigidly to the surface of the virus, blocking exposure of the fusion loop on glycoprotein E1 and therefore preventing the virus from becoming fusogenic. Although Fab 5F10 can neutralize the wild-type virus, it can also bind to a mutant virus without inhibiting fusion or attachment. Although the mutant virus is no longer able to propagate by extracellular budding, it can, however, enter the next cell by traveling through junctional complexes without being intercepted by a neutralizing antibody to the wild-type virus, thus clarifying how cell-to-cell transmission can occur.IMPORTANCEAlphaviral infections are transmitted mainly by mosquitoes. Chikungunya virus (CHIKV), which belongs to theAlphavirusgenus, has a wide distribution in the Old World that has expanded in recent years into the Americas. There are currently no vaccines or drugs against alphaviral infections. Therefore, a better understanding of CHIKV and its associated neutralizing antibodies will aid in the development of effective treatments.

scholarly journals Evaluation of a prototype sub-unit vaccine against equine arteritis virus comprising the entire ectodomain of the virus large envelope glycoprotein (GL): induction of virus-neutralizing antibody and assessment of protection in ponies

2001 ◽  
Vol 82 (10) ◽  
pp. 2425-2435 ◽  
Author(s):  
J. Castillo-Olivares ◽  
A. A. F. de Vries ◽  
M. J. B. Raamsman ◽  
P. J. M. Rottier ◽  
K. Lakhani ◽  
...  
Keyword(s):  
Envelope Glycoprotein ◽  
Neutralizing Antibody ◽  
Equine Arteritis Virus ◽  
Post Vaccination ◽  
Degree Of Protection ◽  
Glycoprotein G ◽  
Virus Excretion ◽  
Unvaccinated Control ◽  
Antibody Titres ◽  
Immunization Study

An Escherichia coli-expressed recombinant protein (6hisGLecto) comprising the entire ectodomain (aa 18–122) of equine arteritis virus (EAV) glycoprotein GL, the immunodominant viral antigen, induced higher neutralizing antibody titres than other GL-derived polypeptides when compared in an immunization study in ponies. The potential of the recombinant GL ectodomain to act as a sub-unit vaccine against EAV was evaluated further in three groups of four ponies vaccinated with doses of 35, 70 or 140 μg of protein. All vaccinated animals developed a virus-neutralizing antibody (VNAb) response with peak titres 1–2 weeks after the administration of a booster on week 5 (VNAb titres of 1·8–3·1), 13 (VNAb titres of 1·4–2·9) or 53 (VNAb titres of 1·2–2·3). Vaccinated and unvaccinated control ponies were infected with EAV at different times post-vaccination to obtain information about the degree of protection relative to the levels of pre-challenge VNAb. Vaccination conferred varying levels of protection, as indicated by reduced or absent pyrexia, viraemia and virus excretion from the nasopharynx. The degree of protection correlated well with the levels of pre-challenge VNAb and, in particular, with levels of virus excretion. These results provide the first evidence that a sub-unit vaccine protects horses against EAV. The use of the sub-unit vaccine in combination with a differential diagnostic test based on other EAV antigens would enable serological discrimination between naturally infected and vaccinated equines.

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

2021 ◽  
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.

scholarly journals Durability of antibody response to vaccination and surrogate neutralization of emerging variants based on SARS-CoV-2 exposure history

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Thomas W. McDade ◽  
Alexis R. Demonbreun ◽  
Amelia Sancilio ◽  
Brian Mustanski ◽  
Richard T. D’Aquila ◽  
...  
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Messenger Rna ◽  
Booster Vaccination ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Post Vaccination ◽  
Vaccine Responses ◽  
Clinical Protection ◽  
Exposure History ◽  
Antibody Levels

AbstractTwo-dose messenger RNA vaccines against the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are highly effective in preventing symptomatic COVID-19 infection. However, the durability of protection is not known, nor is the effectiveness against emerging viral variants. Additionally, vaccine responses may differ based on prior SARS-CoV-2 exposure history. To investigate protection against SARS-CoV-2 variants we measured binding and neutralizing antibody responses following both vaccine doses. We document significant declines in antibody levels three months post-vaccination, and reduced neutralization of emerging variants, highlighting the need to identify correlates of clinical protection to inform the timing of and indications for booster vaccination.

scholarly journals Dynamics of neutralizing antibody responses to SARS-CoV-2 in patients with COVID-19: an observational study

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Xin Xu ◽  
Sheng Nie ◽  
Yanqun Wang ◽  
Quanxin Long ◽  
Hong Zhu ◽  
...  
Keyword(s):  
Protective Immunity ◽  
Neutralization Test ◽  
Neutralizing Antibody ◽  
Antibody Responses ◽  
Half Time ◽  
Peak Titer ◽  
Neutralization Rate ◽  
Repeat Infection ◽  
Post Onset

AbstractOur understanding of the protective immunity, particularly the long-term dynamics of neutralizing antibody (NAbs) response to SARS-CoV-2, is currently limited. We enrolled a cohort of 545 COVID-19 patients from Hubei, China, who were followed up up to 7 months, and determined the dynamics of NAbs to SARS-CoV-2 by using a surrogate virus neutralization test (sVNT). In our validation study, sVNT IC50 titers and the neutralization rate measured at a single dilution (1:20) were well correlated with FRNT titers (r = 0.85 and 0.84, respectively). The median time to seroconversion of NAbs was 5.5 days post onset of symptoms. The rate of positive sVNT was 52% in the first week, reached 100% in the third week, and remained above 97% till 6 months post onset. Quantitatively, NAbs peaked in the fourth week and only a quarter of patients had an estimated peak titer of >1000. NAbs declined with a half-time of 61 days (95% CI: 49–80 days) within the first two months, and the decay deaccelerated to a half-time of 104 days (95% CI: 86–130 days) afterward. The peak levels of NAbs were positively associated with severity of COVID-19 and age, while negatively associated with serum albumin levels. The observation that the low-moderate peak neutralizing activity and fast decay of NAbs in most naturally infected individuals called for caution in evaluating the feasibility of antibody-based therapy and vaccine durability. NAbs response positively correlated with disease severity, warning for the possibility of repeat infection in patients with mild COVID-19.

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