TY - JOUR
T1 - Induction of SARS-CoV-2 neutralizing antibodies by CoronaVac and BNT162b2 vaccines in naïve and previously infected individuals
AU - Muena, Nicolás A.
AU - García-Salum, Tamara
AU - Pardo-Roa, Catalina
AU - Avendaño, María José
AU - Serrano, Eileen F.
AU - Levican, Jorge
AU - Almonacid, Leonardo I.
AU - Valenzuela, Gonzalo
AU - Poblete, Estefany
AU - Strohmeier, Shirin
AU - Salinas, Erick
AU - Muñoz, Andres
AU - Haslwanter, Denise
AU - Dieterle, Maria Eugenia
AU - Jangra, Rohit K.
AU - Chandran, Kartik
AU - González, Claudia
AU - Riquelme, Arnoldo
AU - Krammer, Florian
AU - Tischler, Nicole D.
AU - Medina, Rafael A.
N1 - Funding Information:
The authors reported no potential conflict of interest. The Icahn School of Medicine at Mount Sinai has filed patent applications relating to SARS-CoV-2 serological assays and NDV-based SARS-CoV-2 vaccines which list Florian Krammer as co-inventor. Mount Sinai has spun out a company, Kantaro, to market serological tests for SARS-CoV-2. Florian Krammer has consulted for Merck and Pfizer (before 2020), and is currently consulting for Pfizer, Seqirus, Avimex and Third Rock Ventures. The Krammer laboratory is also collaborating with Pfizer on animal models for SARS-CoV-2. Kartik Chandran is a member of the scientific advisory boards of Integrum Scientific, LLC Biovaxys Technology Corp, and Celdera Medical, LLC; has received royalties from Q2 Solutions and has consulted for Axon Advisors, LLC. Denise Haslwanter, Maria Eugenia Dieterle, Rohit K Jangra and Kartik Chandran, are listed as inventors on a patent application covering the VSV-based SARS2 neutralization assay assigned to Albert Einstein College of Medicine. Rafael Medina has received funding from NIH-Centers of Excellence for Influenza Research and Response (CEIRR) Contract HHSN 75N9301R00028, NIH-Centers of Excellence for Influenza Research and Surveillance (CEIRS) - HHSN272201400008C, the Hope COVID-19 initiative, BHP – UC, FONDECYT 1212023 – ANID Chile and the NIH-NIAID 1U19AI135972: Fluomics: The Next Generation.
Funding Information:
We would like to thanks Luis A. Diaz for excellent clinical assistance during the study period, Zandra Segovia for assistance in patient recruitment and follow-ups and to all individuals that selflessly participated in this study. We also express our deepest gratitude to all the individuals that participated in this study. Work in the Tischler Laboratory was partially funded by FONDECYT 1181799 and Centro Ciencia & Vida, FB210008, Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia grants from the Agencia Nacional de Investigación y Desarrollo (ANID) of Chile. Work in the Medina Laboratory was based on protocols and the study set-up used for influenza virus established in part with the support of the PIA ACT 1408, FONDECYT 1161971, 1212023, and CONICYT REDES180170 grants from ANID of Chile, the FLUOMICS Consortium (NIH-NIAD grant U19AI135972) and the Center for Research on Influenza Pathogenesis (CRIP), an NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C) to RAM and FK. Additionally, work in the Krammer laboratory was partially funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051, by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611 (5384); and by anonymous donors. Work in the Chandran laboratory was partially supported by NIH grant R01AI132633. CPR and JL conducted this work as part of their Postdoctoral grants FONDECYT 3190706 and 3190648, respectively. MJA and ES conducted this work as part of their Ph.D. Thesis, under Programa de Doctorado en Ciencias Biológicas mención Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Cátolica de Chile. MJA was funded by the ANID Becas/Doctorado Nacional 21212258 scholarship and ES was funded by a scholarship from Vicerrectoría de Investigación de la Escuela de Graduados, Pontificia Universidad Católica de Chile. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Funding Information:
We would like to thanks Luis A. Diaz for excellent clinical assistance during the study period, Zandra Segovia for assistance in patient recruitment and follow-ups and to all individuals that selflessly participated in this study. We also express our deepest gratitude to all the individuals that participated in this study. Work in the Tischler Laboratory was partially funded by FONDECYT 1181799 and Centro Ciencia & Vida, FB210008, Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia grants from the Agencia Nacional de Investigación y Desarrollo (ANID) of Chile. Work in the Medina Laboratory was based on protocols and the study set-up used for influenza virus established in part with the support of the PIA ACT 1408, FONDECYT 1161971, 1212023, and CONICYT REDES180170 grants from ANID of Chile, the FLUOMICS Consortium (NIH-NIAD grant U19AI135972) and the Center for Research on Influenza Pathogenesis (CRIP), an NIAID Center of Excellence for Influenza Research and Surveillance (CEIRS, contract # HHSN272201400008C) to RAM and FK. Additionally, work in the Krammer laboratory was partially funded by the NIAID Collaborative Influenza Vaccine Innovation Centers (CIVIC) contract 75N93019C00051, by the generous support of the JPB Foundation and the Open Philanthropy Project (research grant 2020-215611 (5384); and by anonymous donors. Work in the Chandran laboratory was partially supported by NIH grant R01AI132633. CPR and JL conducted this work as part of their Postdoctoral grants FONDECYT 3190706 and 3190648, respectively. MJA and ES conducted this work as part of their Ph.D. Thesis, under Programa de Doctorado en Ciencias Biológicas mención Genética Molecular y Microbiología, Facultad de Ciencias Biológicas, Pontificia Universidad Cátolica de Chile. MJA was funded by the ANID Becas/Doctorado Nacional 21212258 scholarship and ES was funded by a scholarship from Vicerrectoría de Investigación de la Escuela de Graduados, Pontificia Universidad Católica de Chile. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Publisher Copyright:
© 2022 The Authors
PY - 2022/4
Y1 - 2022/4
N2 - Background: A major challenge of the SARS-CoV-2 pandemic is to better define “protective thresholds” to guide the global response. We aimed to characterize the longitudinal dynamics of the antibody responses in naturally infected individuals in Chile and compared them to humoral responses induced after immunization with CoronaVac-based on an inactivated whole virus -or the BNT162b2- based on mRNA-vaccines. We also contrasted them with the respective effectiveness and efficacy data available for both vaccines. Methods: We determined and compared the longitudinal neutralizing (nAb) and anti-nucleocapsid (anti-N) antibody responses of 74 COVID-19 individuals (37 outpatient and 37 hospitalized) during the acute disease and convalescence. We also assessed the antibody boosting of 36 of these individuals who were immunized after convalescence with either the CoronaVac (n = 30) or the BNT162b2 (n = 6) vaccines. Antibody titres were also measured for 50 naïve individuals immunized with two doses of CoronaVac (n = 35) or BNT162b2 (n = 15) vaccines. The neutralizing level after vaccination was compared to those of convalescent individuals and the predicted efficacy was estimated. Findings: SARS-CoV-2 infection induced robust nAb and anti-N antibody responses lasting >9 months, but showing a rapid nAb decay. After convalescence, nAb titres were significantly boosted by vaccination with CoronaVac or BNT162b2. In naïve individuals, the calculated mean titre induced by two doses of CoronaVac or BNT162b2 was 0·2 times and 5.2 times, respectively, that of convalescent individuals, which has been proposed as threshold of protection. CoronaVac induced no or only modest anti-N antibody responses. Using two proposed logistic models, the predicted efficacy of BNT162b2 was estimated at 97%, in close agreement with phase 3 efficacy studies, while for CoronaVac it was ∼50% corresponding to the lowest range of clinical trials and below the real-life data from Chile (from February 2 through May 1, 2021 during the predominant circulation of the Gamma variant), where the estimated vaccine effectiveness to prevent COVID-19 was 62·8–64·6%. Interpretation: The decay of nAbs titres in previously infected individuals over time indicates that vaccination is needed to boost humoral memory responses. Immunization of naïve individuals with two doses of CoronaVac induced nAbs titres that were significantly lower to that of convalescent patients, and similar to vaccination with one dose of BTN162b2. The real life effectiveness for CoronaVac in Chile was higher than estimated; indicating that lower titres and additional cellular immune responses induced by CoronaVac might afford protection in a highly immunized population. Nevertheless, the lower nAb titre induced by two doses of CoronaVac as compared to the BTN162b2 vaccine in naïve individuals, highlights the need of booster immunizations over time to maintain protective levels of antibody, particularly with the emergence of new SARS-CoV-2 variants. Funding: FONDECYT 1161971, 1212023, 1181799, FONDECYT Postdoctorado 3190706 and 3190648, ANID Becas/Doctorado Nacional 21212258, PIA ACT 1408, CONICYT REDES180170, Centro Ciencia & Vida, FB210008, Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia grants from the Agencia Nacional de Investigación y Desarrollo (ANID) of Chile; NIH-NIAD grants U19AI135972, R01AI132633 and contracts HHSN272201400008C and 75N93019C00051; the JPB Foundation, the Open Philanthropy Project grant 2020-215611 (5384); and by anonymous donors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
AB - Background: A major challenge of the SARS-CoV-2 pandemic is to better define “protective thresholds” to guide the global response. We aimed to characterize the longitudinal dynamics of the antibody responses in naturally infected individuals in Chile and compared them to humoral responses induced after immunization with CoronaVac-based on an inactivated whole virus -or the BNT162b2- based on mRNA-vaccines. We also contrasted them with the respective effectiveness and efficacy data available for both vaccines. Methods: We determined and compared the longitudinal neutralizing (nAb) and anti-nucleocapsid (anti-N) antibody responses of 74 COVID-19 individuals (37 outpatient and 37 hospitalized) during the acute disease and convalescence. We also assessed the antibody boosting of 36 of these individuals who were immunized after convalescence with either the CoronaVac (n = 30) or the BNT162b2 (n = 6) vaccines. Antibody titres were also measured for 50 naïve individuals immunized with two doses of CoronaVac (n = 35) or BNT162b2 (n = 15) vaccines. The neutralizing level after vaccination was compared to those of convalescent individuals and the predicted efficacy was estimated. Findings: SARS-CoV-2 infection induced robust nAb and anti-N antibody responses lasting >9 months, but showing a rapid nAb decay. After convalescence, nAb titres were significantly boosted by vaccination with CoronaVac or BNT162b2. In naïve individuals, the calculated mean titre induced by two doses of CoronaVac or BNT162b2 was 0·2 times and 5.2 times, respectively, that of convalescent individuals, which has been proposed as threshold of protection. CoronaVac induced no or only modest anti-N antibody responses. Using two proposed logistic models, the predicted efficacy of BNT162b2 was estimated at 97%, in close agreement with phase 3 efficacy studies, while for CoronaVac it was ∼50% corresponding to the lowest range of clinical trials and below the real-life data from Chile (from February 2 through May 1, 2021 during the predominant circulation of the Gamma variant), where the estimated vaccine effectiveness to prevent COVID-19 was 62·8–64·6%. Interpretation: The decay of nAbs titres in previously infected individuals over time indicates that vaccination is needed to boost humoral memory responses. Immunization of naïve individuals with two doses of CoronaVac induced nAbs titres that were significantly lower to that of convalescent patients, and similar to vaccination with one dose of BTN162b2. The real life effectiveness for CoronaVac in Chile was higher than estimated; indicating that lower titres and additional cellular immune responses induced by CoronaVac might afford protection in a highly immunized population. Nevertheless, the lower nAb titre induced by two doses of CoronaVac as compared to the BTN162b2 vaccine in naïve individuals, highlights the need of booster immunizations over time to maintain protective levels of antibody, particularly with the emergence of new SARS-CoV-2 variants. Funding: FONDECYT 1161971, 1212023, 1181799, FONDECYT Postdoctorado 3190706 and 3190648, ANID Becas/Doctorado Nacional 21212258, PIA ACT 1408, CONICYT REDES180170, Centro Ciencia & Vida, FB210008, Financiamiento Basal para Centros Científicos y Tecnológicos de Excelencia grants from the Agencia Nacional de Investigación y Desarrollo (ANID) of Chile; NIH-NIAD grants U19AI135972, R01AI132633 and contracts HHSN272201400008C and 75N93019C00051; the JPB Foundation, the Open Philanthropy Project grant 2020-215611 (5384); and by anonymous donors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
KW - COVID-19
KW - Neutralizing antibody persistence
KW - SARS-CoV-2 vaccines
KW - Serological response
KW - Vaccination boost
UR - http://www.scopus.com/inward/record.url?scp=85127124356&partnerID=8YFLogxK
U2 - 10.1016/j.ebiom.2022.103972
DO - 10.1016/j.ebiom.2022.103972
M3 - Article
C2 - 35366624
AN - SCOPUS:85127124356
SN - 2352-3964
VL - 78
JO - eBioMedicine
JF - eBioMedicine
M1 - 103972
ER -