Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile

Beltrán-Pavez, Carolina; Riquelme-Barrios, Sebastián; Oyarzún-Arrau, Aarón; Gaete-Argel, Aracelly; González-Stegmaier, Roxana; Cereceda-Solis, Karina; Aguirre, Adam; Travisany, Dante; Palma-Vejares, Ricardo; Barriga, Gonzalo P.; Gaggero, Aldo; Martínez-Valdebenito, Constanza; Corre, Nicole Le; Ferrés, Marcela; Balcells, María Elvira; Fernández, Jorge Onrubia; Ramı́rez, Eugenio; Villarroel, Franz; Valiente-Echeverría, Fernando; Soto-Rifo, Ricardo

doi:10.1126/sciadv.abe6855

Cited by 36 publications

(53 citation statements)

References 56 publications

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“…Pseudotyped viruses carrying different SARS-CoV-2 spike proteins were prepared as we previously described 12 . Briefly, HIV-1-based SARS-CoV-2 pseudotypes were produced in…”

Section: Infectivity Assaymentioning

confidence: 99%

“…Pseudotyped virus neutralization assays were performed essentially as we previously described 12 . Briefly, serial dilutions of the plasma samples (1:4 to 1:8748) were prepared in DMEM with 10% fetal bovine serum and incubated with 5 ng of p24 of each pseudotyped virus during 1h at 37 °C and then, 1x10 4 of HEK-ACE2 cells were added to each well.…”

Section: Neutralization Assaymentioning

confidence: 99%

“…Here, we used our previously described pseudotyped virus neutralization assay 12 to determine the impact of the Lambda variant on the neutralizing antibodies responses elicited by the inactivated virus vaccine CoronaVac. Our data show that mutations present in the spike protein of the Lambda variant confer increased infectivity and escape to neutralizing antibodies elicited by the inactivated virus vaccine CoronaVac.…”

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confidence: 99%

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Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

Acevedo

Alonso-Palomares

Bustamante

et al. 2021

Preprint

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Background: The newly described SARS-CoV-2 lineage C.37 was recently classified as a variant of interest by the WHO (Lambda variant) based on its high circulation rates in South American countries and the presence of critical mutations in the spike protein. The impact of such mutations in infectivity and immune escape from neutralizing antibodies are entirely unknown. Methods: We performed a pseudotyped virus neutralization assay and determined the impact of the Lambda variant on infectivity and immune escape using plasma samples from healthcare workers (HCW) from two centers in Santiago, Chile who received the two-doses scheme of the inactivated virus vaccine CoronaVac. Results: We observed an increased infectivity mediated by the Lambda spike protein that was even higher than that of the D614G (lineage B) or the Alpha and Gamma variants. Compared to the Wild type (lineage A), neutralization was decreased by 3.05-fold for the Lambda variant while it was 2.33-fold for the Gamma variant and 2.03-fold for the Alpha variant. Conclusions: Our results indicate that mutations present in the spike protein of the Lambda variant of interest confer increased infectivity and immune escape from neutralizing antibodies elicited by CoronaVac. These data reinforce the idea that massive vaccination campaigns in countries with high SARS-CoV-2 circulation must be accompanied by strict genomic surveillance allowing the identification of new isolates carrying spike mutations and immunology studies aimed to determine the impact of these mutations in immune escape and vaccines breakthrough.

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“…Pseudotyped viruses carrying different SARS-CoV-2 spike proteins were prepared as we previously described 12 . Briefly, HIV-1-based SARS-CoV-2 pseudotypes were produced in…”

Section: Infectivity Assaymentioning

confidence: 99%

Section: Neutralization Assaymentioning

confidence: 99%

mentioning

confidence: 99%

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Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

Acevedo

Alonso-Palomares

Bustamante

et al. 2021

Preprint

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“…Pseudotyped viral particles were produced by transient transfection of HEK293T cells using polyethylenimine (PEI) and plasmids pNL4.3-ΔEnv-Firefly and pCMV14–3X-Flag–SARS-CoV-2 SΔ19C (lineage A) in a 1:1 ratio as we described (7). The viral particles were diluted with 50% in fetal bovine serum (Sigma-Aldrich) and stored at -80°C.…”

Section: Elisamentioning

confidence: 99%

Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 S antibodies

Vargas

Valdivieso

Tempio

et al. 2022

Preprint

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Background: Chile was severely affected by COVID19 outbreaks but was also one of the first countries to start a nationwide program to vaccinate against the disease. Furthermore, Chile became one of the fastest countries to inoculate a high percentage of the target population and implemented homologous and heterologous booster schemes in late 2021 to prevent potential immunological waning. The aim of this study is to compare the immunogenicity and time course of the humoral response elicited by the CoronaVac vaccine in combination with homologous versus heterologous boosters. Methods and Findings: We compared the immunogenicity of two doses of CoronaVac and BNT162b2 vaccines and studied the effect of different booster regimes in the Chilean population. Our results demonstrate that a two-dose vaccination scheme with CoronaVac induces lower levels of anti-SARS-CoV-2 S antibodies than BNT162b2 in a broad age range. Furthermore, antibody production declines with time in individuals vaccinated with CoronaVac and less noticeably, with BNT162b2. Remarkably, analysis of booster schemes revealed that individuals vaccinated with two doses of CoronaVac generate immunological memory against the SARS-CoV-2 ancestral strain, which can be re-activated with homologous or heterologous (BNT162b2 and ChAdOx1) boosters. Nevertheless, the magnitude of the antibody response with the heterologous booster regime was considerably higher and persistent (over 100 days) than the responses induced by the homologous scheme. Conclusions: Two doses of CoronaVac induces antibody titers against the SARS-CoV-2 ancestral strain which are lower in magnitude than those induced by the BNT162b2 vaccine. However, the response induced by CoronaVac can be greatly potentiated with a heterologous booster scheme with BNT162b2 or ChAdOx1 vaccines. Furthermore, the heterologous booster regimes induce a durable antibody response which does not show signs of decay 3 months after the booster dose.

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“…We generated pseudotyped viruses carrying either the ancestral SARS-CoV-2 spike protein (wild type; lineage A), the spike protein carrying the D614G mutation (lineage B) as well as the spike from variants Alpha (lineage B.1.1.7), Gamma (lineage P.1) and Lambda (lineage C.37) as previously described 6 . Neutralization assays using the pseudotyped virus carrying the ancestral spike revealed that the geometric mean of the ID 50 titer was 138.7 (95% CI, 114.7 to 167.7) for the individuals receiving the inactivated virus vaccine, while it was 803.8 (95% CI, 652.9 to 989.6) for those inoculated with the mRNA vaccine (Fig.…”

Section: Mainmentioning

confidence: 99%

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

Acevedo

Alonso-Palomares

et al. 2021

Preprint

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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.

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Insights into neutralizing antibody responses in individuals exposed to SARS-CoV-2 in Chile

Cited by 36 publications

References 56 publications

Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

Infectivity and immune escape of the new SARS-CoV-2 variant of interest Lambda

Serological study of CoronaVac vaccine and booster doses in Chile: immunogenicity and persistence of anti-SARS-CoV-2 S antibodies

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

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