scholarly journals Reduced levels of convalescent neutralizing antibodies against SARS-CoV-2 B.1+L249S+E484K lineage

2021 ◽  
Author(s):  
Diego Alejandro Alvarez Diaz ◽  
Katherine Laiton Donato ◽  
Orlando Alfredo Torres Garcia ◽  
Hector Alejandro Ruiz Moreno ◽  
Carlos E Franco Munoz ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Epidemiological Data ◽  
Laboratory Characterization ◽  
Previous Infection ◽  
Surveillance Programs ◽  
Antibody Titers ◽  
Study Support

The E484K mutation at the SARS-CoV-2 Spike protein emerged independently in different variants around the world, probably as part of the ongoing adaptation of the virus to the human host, and has been widely associated with immune escape from neutralizing antibodies generated during previous infection or vaccination. In this work, the B.1+L249S+E484K lineage was isolated along with A.1, B.1.420 and B.1.111 SARS-CoV-2 lineages without the E484K mutation and the neutralizing titer of convalescent sera was compared using microneutralization assays. While no significant differences in the neutralizing antibody titers were found between A1 and B lineages without the E484K mutation, the neutralizing titers against B.1+L249S+E484K were 1.5, 1.9, 2.1, and 1.3-fold lower than against A.1, B.1.420, B.1.111-I, and B.1.111-II, respectively. However, molecular epidemiological data indicate that there is no increase in the transmissibility rate associated with this new lineage. Hence, although the evidence provided in this study support a Variant of Interest Status (VOI) for the B1+L249S+E484K lineage, enhanced laboratory characterization of this particular lineage and other emerging lineages with the E484K mutation should be carried out in individuals with immunity acquired by natural infection and vaccination. This study accentuated the capability of new variants with the E484K mutation to be resistant to neutralization by humoral immunity, and therefore the need to intensify surveillance programs.

scholarly journals SARS-CoV-2 binding and neutralizing antibody levels after vaccination with Ad26.COV2.S predict durable protection in rhesus macaques

2021 ◽  
Author(s):  
Ramon Roozendaal ◽  
Laura Solforosi ◽  
Daniel Stieh ◽  
Jan Serroyen ◽  
Roel Straetemans ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Preliminary Evidence ◽  
Correlates Of Protection ◽  
Antibody Titers ◽  
Antibody Levels ◽  
The Relationship

The first COVID-19 vaccines have recently gained authorization for emergency use.1,2 At this moment, limited knowledge on duration of immunity and efficacy of these vaccines is available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short lived,3,4 and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection.5 Here we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike (S) protein in rhesus macaques6,7,8 and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We find that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of S-binding and neutralizing antibodies. These results suggest that Ad26.COV2.S could confer durable protection in humans and that immunological correlates of protection may enable the prediction of durability of protection.

scholarly journals Antibody Response to the BNT162b2 mRNA COVID-19 Vaccine in Subjects with Prior SARS-CoV-2 Infection

Viruses ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 422
Author(s):  
Federico Gobbi ◽  
Dora Buonfrate ◽  
Lucia Moro ◽  
Paola Rodari ◽  
Chiara Piubelli ◽  
...  
Keyword(s):  
Antibody Response ◽  
Neutralizing Antibodies ◽  
Natural Infection ◽  
Vaccine Dose ◽  
Neutralizing Antibody ◽  
Immune Memory ◽  
Effective Response ◽  
Infected People ◽  
Significant Difference ◽  
Antibody Titers

Although antibody levels progressively decrease following SARS-CoV-2 infection, the immune memory persists for months. Thus, individuals who naturally contracted SARS-CoV-2 are expected to develop a more rapid and sustained response to COVID-19 vaccines than naïve individuals. In this study, we analyzed the dynamics of the antibody response to the BNT162b2 mRNA COVID-19 vaccine in six healthcare workers who contracted SARS-CoV-2 in March 2020, in comparison to nine control subjects without a previous infection. The vaccine was well tolerated by both groups, with no significant difference in the frequency of vaccine-associated side effects, with the exception of local pain, which was more common in previously infected subjects. Overall, the titers of neutralizing antibodies were markedly higher in response to the vaccine than after natural infection. In all subjects with pre-existing immunity, a rapid increase in anti-spike receptor-binding domain (RBD) IgG antibodies and neutralizing antibody titers was observed one week after the first dose, which seemed to act as a booster. Notably, in previously infected individuals, neutralizing antibody titers 7 days after the first vaccine dose were not significantly different from those observed in naïve subjects 7 days after the second vaccine dose. These results suggest that, in previously infected people, a single dose of the vaccine might be sufficient to induce an effective response.

scholarly journals Passive transfer of Ad26.COV2.S-elicited IgG from humans attenuates SARS-CoV-2 disease in hamsters

npj Vaccines ◽  
2022 ◽  
Vol 7 (1) ◽  
Author(s):  
Lisa H. Tostanoski ◽  
Abishek Chandrashekar ◽  
Shivani Patel ◽  
Jingyou Yu ◽  
Catherine Jacob-Dolan ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adoptive Transfer ◽  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Specific Binding ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Transfer Model ◽  
Golden Syrian Hamster ◽  
Antibody Titers

AbstractSARS-CoV-2 Spike-specific binding and neutralizing antibodies, elicited either by natural infection or vaccination, have emerged as potential correlates of protection. An important question, however, is whether vaccine-elicited antibodies in humans provide direct, functional protection from SARS-CoV-2 infection and disease. In this study, we explored directly the protective efficacy of human antibodies elicited by Ad26.COV2.S vaccination by adoptive transfer studies. IgG from plasma of Ad26.COV2.S vaccinated individuals was purified and transferred into naïve golden Syrian hamster recipients, followed by intra-nasal challenge of the hamsters with SARS-CoV-2. IgG purified from Ad26.COV2.S-vaccinated individuals provided dose-dependent protection in the recipient hamsters from weight loss following challenge. In contrast, IgG purified from placebo recipients provided no protection in this adoptive transfer model. Attenuation of weight loss correlated with binding and neutralizing antibody titers of the passively transferred IgG. This study suggests that Ad26.COV2.S-elicited antibodies in humans are mechanistically involved in protection against SARS-CoV-2.

scholarly journals Low neutralizing antibody titers against the Mu variant of SARS-CoV-2 in BNT162b2 vaccinated individuals

2021 ◽  
Author(s):  
Diego Alejandro Alvarez-Diaz ◽  
Ana L Munoz ◽  
Pilar Tavera-Rodriguez ◽  
Maria T Herrera-Sepulveda ◽  
Hector A Ruiz-Moreno ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Spike Protein ◽  
World Health ◽  
The World ◽  
Need To Evaluate ◽  
Surveillance Programs ◽  
Antibody Titers ◽  
Epidemiological Impact ◽  
Health Organization

Background Global surveillance programs for the virus that causes COVID-19 are showing the emergence of variants with mutations in the Spike protein, including the Mu variant, recently declared as a Variant of Interest (VOI) by the World Health Organization. Because these types of variants can be more infectious or less susceptible to antiviral treatments and vaccine-induced antibodies. Objectives To evaluate the sensitivity of the Mu variant (B.1.621) to neutralizing antibodies induced by the BNT162b2 vaccine. Study design Three of the most predominant SARS-CoV-2 variants in Colombia during the epidemiological peaks of 2021 were isolated. Microneutralization assays were performed by incubating 120 TCDI50 of each SARS-CoV-2 isolate with five 2-fold serial dilutions of sera from 14 BNT162b2 vaccinated volunteers. The MN50 titer was calculated by the Reed-Muench formula Results The three isolated variants were Mu, a Variant of Interest (VOI), Gamma, a variant of concern (VOC), and B.1.111 that lacks genetic markers associated with greater virulence. At the end of August, the Mu and Gamma variants were widely distributed in Colombia. Mu was predominant (49%), followed by Gamma (25%). In contrast, B.1.111 became almost undetectable. The evaluation of neutralizing antibodies suggests that patients vaccinated with BNT162-2 generate neutralizing antibody titers against the Mu variant at significantly lower concentrations relative to B.1.111 and Gamma. Conclusions This study shows the importance of continuing with surveillance programs of emerging variants as well as the need to evaluate the neutralizing antibody response induced by other vaccines circulating in the country against Mu and other variants with high epidemiological impact.

scholarly journals SARS-CoV-2 binding and neutralizing antibody levels after Ad26.COV2.S vaccination predict durable protection in rhesus macaques

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ramon Roozendaal ◽  
Laura Solforosi ◽  
Daniel J. Stieh ◽  
Jan Serroyen ◽  
Roel Straetemans ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Protective Efficacy ◽  
Rhesus Macaques ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Preliminary Evidence ◽  
Correlates Of Protection ◽  
Antibody Titers ◽  
Antibody Levels ◽  
The Relationship

AbstractSeveral COVID-19 vaccines have recently gained authorization for emergency use. Limited knowledge on duration of immunity and efficacy of these vaccines is currently available. Data on other coronaviruses after natural infection suggest that immunity to SARS-CoV-2 might be short-lived, and preliminary evidence indicates waning antibody titers following SARS-CoV-2 infection. In this work, we model the relationship between immunogenicity and protective efficacy of a series of Ad26 vectors encoding stabilized variants of the SARS-CoV-2 Spike protein in rhesus macaques and validate the analyses by challenging macaques 6 months after immunization with the Ad26.COV2.S vaccine candidate that has been selected for clinical development. We show that Ad26.COV2.S confers durable protection against replication of SARS-CoV-2 in the lungs that is predicted by the levels of Spike-binding and neutralizing antibodies, indicating that Ad26.COV2.S could confer durable protection in humans and immunological correlates of protection may enable the prediction of durability of protection.

scholarly journals Attenuated Influenza Virions Expressing the SARS-CoV-2 Receptor-Binding Domain Induce Neutralizing Antibodies in Mice

Viruses ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 987 ◽  
Author(s):  
Andrea N. Loes ◽  
Lauren E. Gentles ◽  
Allison J. Greaney ◽  
Katharine H. D. Crawford ◽  
Jesse D. Bloom
Keyword(s):  
Influenza Virus ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Reverse Genetics ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Receptor Binding Domain ◽  
Antibody Titers

An effective vaccine is essential for controlling the spread of the SARS-CoV-2 virus. Here, we describe an influenza virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (~1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for the production of influenza vaccines.

scholarly journals Neutralization of the emerging SARS-CoV-2 variant Lambda by antibodies elicited by inactivated virus and mRNA vaccines

2021 ◽  
Author(s):  
Mónica Acevedo ◽  
Luis Alonso-Palomares ◽  
Marco Montes de Oca ◽  
Andrés Bustamante ◽  
Aldo Gaggero ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Neutralizing Antibody ◽  
Neutralization Capacity ◽  
Antigenic Sites ◽  
Antibody Titers ◽  
Different Levels

Abstract Here, we used pseudotyped viruses to characterize the neutralization capacity of antibodies elicited by the CoronaVac and BNT162b2 vaccines against the emerging variant of interest Lambda. We observed that BNT162b2 elicits higher neutralizing antibody titers than CoronaVac, ranging from 5.8-fold for the ancestral spike to 9.4-fold for the Lambda variant. Neutralization against D614G, Alpha, Gamma, and Lambda variants was reduced between 1.78 to 3.05-fold for CoronaVac and 1.10 to 1.87-fold for BNT162b2. Structural analyses of the Lambda spike show significant changes in antigenic sites including the 246–252 deletion in an antigenic supersite at the NTD loop and, L452Q/F490S within the RBD that may account for immune escape. Our analysis of pseudotyped viruses also suggests increased infectivity driven by the Lambda spike. Together, our data indicate that inactivated virus and mRNA vaccines elicit different levels of neutralizing antibodies with different potency to neutralize SARS-CoV-2 variants, including the emergent variant Lambda.

scholarly journals Antibodies elicited by SARS-CoV-2 infection and boosted by vaccination neutralize an emerging variant and SARS-CoV-1

2021 ◽  
Author(s):  
Leonidas Stamatatos ◽  
Julie Czartoski ◽  
Yu-Hsin Wan ◽  
Leah J. Homad ◽  
Vanessa Rubin ◽  
...  
Keyword(s):  
South Africa ◽  
Immune Response ◽  
Monoclonal Antibodies ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Fold Increase ◽  
Cd4 T Cell ◽  
Cell Responses ◽  
Previous Infection ◽  
Antibody Titers

AbstractThe emergence of SARS-CoV-2 variants raises concerns about their resistance to neutralizing antibodies elicited from previous infection, or from vaccination. Here we examined whether sera and monoclonal antibodies from convalescent donors, prior to and following a single immunization with the Pfizer or Moderna mRNA vaccines, neutralize the Wuhan-Hu-1 strain and a variant, B.1.351 from South Africa. Pre-vaccination sera weakly neutralized Wuhan-Hu-1 and sporadically neutralized B.1.351. Immunization with either vaccine generated anamnestic B and CD4+ T cell responses and a 1000-fold increase in neutralizing antibody titers against both strains and SARS-CoV-1. Neutralization was likely due to anti-RBD and anti-S2 antibodies. Our study highlights the importance of vaccination of both uninfected and of previously infected subjects, as the elicited immune response will neutralize distinct viral strains.

scholarly journals Attenuated influenza virions expressing the SARS-CoV-2 receptor-binding domain induce neutralizing antibodies in mice

2020 ◽  
Author(s):  
Andrea N. Loes ◽  
Lauren E. Gentles ◽  
Allison J. Greaney ◽  
Katharine H. D. Crawford ◽  
Jesse D. Bloom
Keyword(s):  
Influenza Virus ◽  
Receptor Binding ◽  
Neutralizing Antibodies ◽  
Reverse Genetics ◽  
Natural Infection ◽  
Neutralizing Antibody ◽  
Binding Domain ◽  
Effective Vaccine ◽  
Receptor Binding Domain ◽  
Antibody Titers

AbstractAn effective vaccine is essential to controlling the spread of SARS-CoV-2 virus. Here, we describe an influenza-virus-based vaccine for SARS-CoV-2. We incorporated a membrane-anchored form of the SARS-CoV-2 Spike receptor binding domain (RBD) in place of the neuraminidase (NA) coding sequence in an influenza virus also possessing a mutation that reduces the affinity of hemagglutinin for its sialic acid receptor. The resulting ΔNA(RBD)-Flu virus can be generated by reverse genetics and grown to high titers in cell culture. A single-dose intranasal inoculation of mice with ΔNA(RBD)-Flu elicits serum neutralizing antibody titers against SAR-CoV-2 comparable to those observed in humans following natural infection (∼1:200). Furthermore, ΔNA(RBD)-Flu itself causes no apparent disease in mice. It might be possible to produce a vaccine similar to ΔNA(RBD)-Flu at scale by leveraging existing platforms for production of influenza vaccines.

scholarly journals Estimates of reduced vaccine effectiveness against hospitalization, infection, transmission and symptomatic disease of a new SARS-CoV-2 variant, Omicron (B.1.1.529), using neutralizing antibody titers

2021 ◽  
Author(s):  
Billy J Gardner ◽  
A. Marm Kilpatrick
Keyword(s):  
Neutralizing Antibodies ◽  
Immune Escape ◽  
Severe Disease ◽  
Neutralizing Antibody ◽  
Vaccine Effectiveness ◽  
Vaccine Protection ◽  
Infection Transmission ◽  
Symptomatic Disease ◽  
Antibody Titers ◽  
Protection Against Infection

The emergence of the Omicron variant (B.1.1.529) of SARS-CoV-2 has raised concerns about how mutations in the spike protein might influence immune escape and vaccine protection against infection and disease, COVID-19. Initial estimates of immune escape measure neutralizing antibody titers, which have been shown to be a correlate of protection for COVID-19, but vary among studies. However, no studies have examined variation in vaccine effectiveness (VE) using estimated reductions in neutralizing antibody titers across virus variants. We quantified consistency in relative neutralizing antibody titers across studies. We then examined relationships between variant-specific reductions in neutralizing antibodies and protection against documented infection, symptomatic disease, and hospitalizations across variants and vaccines. We found considerable variation in variant-specific neutralizing antibody titers between studies, but within-study comparisons across variants were far more robust. There was insufficient data to estimate VE for a single vaccine across variants, especially for higher levels of immune evasion (>7-fold reductions in neutralizing antibody titers) observed with the Omicron variant (40-fold). Instead, we leveraged variation among both vaccines and virus variants to estimate VE - neutralizing antibody titer relationships across a 30 to 100-fold range of neutralizing antibody titers reduction. Omicron increased the risk of hospitalization four to five-fold and increased the risk of symptomatic disease seven to ten-fold for mRNA vaccinees, with similar relative effects for recently vaccinated, or individuals with waned antibody titers. Third doses restored titers and protection to levels similar to waned immunity against Delta. Overall, these analyses indicate that vaccine effectiveness against severe disease is significantly diminished for waned individuals, and protection against infection, symptomatic disease and transmission is nearly eliminated. However, third doses significantly ameliorate these reductions but only restore protection to levels equivalent to waned protection against the Delta variant. The invasion of Omicron is likely to result in widespread infection, and substantial hospitalizations unless widespread boosting of immunity occurs.

Sign in / Sign up

Export Citation Format

Share Document