TY - JOUR
T1 - Age-dependent impairment in antibody responses elicited by a homologous CoronaVac booster dose
AU - Yale SARS-CoV-2 Genomic Surveillance Initiative
AU - Filardi, Bruno Andraus
AU - Monteiro, Valter Silva
AU - Schwartzmann, Pedro Vellosa
AU - Martins, Vivian do Prado
AU - Zucca, Luis Eduardo Rosa
AU - Baiocchi, Gabriela Crispim
AU - Malik, Amyn A.
AU - Silva, Julio
AU - Hahn, Anne M.
AU - Chen, Nicholas F.G.
AU - Pham, Kien
AU - Pérez-Then, Eddy
AU - Miric, Marija
AU - Brache, Vivian
AU - Cochon, Leila
AU - Larocca, Rafael A.
AU - Mendez, Roberto Della Rosa
AU - Silveira, Douglas Bardini
AU - Pinto, Aguinaldo Roberto
AU - Croda, Julio
AU - Yildirim, Inci
AU - Omer, Saad B.
AU - Ko, Albert I.
AU - Vermund, Sten H.
AU - Grubaugh, Nathan D.
AU - Iwasaki, Akiko
AU - Lucas, Carolina
N1 - Funding Information:
Acknowledgments:W eareverygratefultoallstudyparticipantswhodonatedspecimensfor thisstudy.W ethankM.Linehanfortechnicalandlogisticalassistance.W ealsowouldliketo thankD.Mucida,whoprovidedinsightandexpertisethatgreatlyassistedthedataanalysisand commentsthatsignificantlyimprovedthismanuscript.TheBrazilianteamisgratefulto M.Krieger(VicePresidentofFioCruz),B.Furtado,andV .BertolloGomesPorto(Programa NacionaldeImunização)andtoE.Caires(SECO VID, Multiplan,InstitutodoCancerBrasilde EnsinoePesquisa,CAPEDRibeirãoShopping),M.Kobayashi,ÁgoraGroup,andthePec.T eam forcontributionstothesetupofthestudyplatform.W ealsothankG.Galbiatiforthe pharmaceuticalassistance;L.Jarduli,G.Faustino,L.Zucca,C.Bonafim,J.Anelli,L.Prado,and O.Graçãofortechnicalassistance.TheDominicanRepublicteamisgratefultoM.Caram (PROFAMILIA)andM.Kelly(Labora torio deReferencia)forcontributionstothesetupofthe studyplatform.TheCoronaVa cvaccinewaspro vided bytheBraziliangovernment,andthe ChAdOx1-SvaccinewasprovidedbyFioCruzBrazil.Funding:TheBraziliancohortsetupteam wassupportedbyAstraZenecaexternallysponsoredscientificresearchprogram.A.I.andN.D.G. arerecipientsoftheFastGrantfromEmergentVenturesattheMercatusCenter.N.D.G.andC.L. weresupportedbytheCentersforDiseaseControlandPreventionBroadAgency Announcement Contract 75D30122C14697. A.I. was supported by the W omen ’s Health ResearchatYalePilotProjectProgr am, MathersFoundation,theLudwigFamilyFoundation,the DepartmentofInternalMedicineattheYaleSchoolofMedicine,YaleSchoolofPublicHealth, theBeatriceKleinbergNeuwirthFund,andtheHowardHughesMedicalInstitute.V .S.M. was supportedbytheCAPES-YALEfellowship.Authorcontributions:B.A.F ., A.I.,andC.L.conceived
Funding Information:
We are very grateful to all study participants who donated specimens for this study. We thank M. Linehan for technical and logistical assistance. We also would like to thank D. Mucida, who provided insight and expertise that greatly assisted the data analysis and comments that significantly improved this manuscript. The Brazilian team is grateful to M. Krieger (Vice President of FioCruz), B. Furtado, and V. Bertollo Gomes Porto (Programa Nacional de Imunização) and to E. Caires (SECOVID, Multiplan, Instituto do Cancer Brasil de Ensino e Pesquisa, CAPED Ribeirão Shopping), M. Kobayashi, Ágora Group, and the Pec. Team for contributions to the setup of the study platform. We also thank G. Galbiati for the pharmaceutical assistance; L. Jarduli, G. Faustino, L. Zucca, C. Bonafim, J. Anelli, L. Prado, and O. Gração for technical assistance. The Dominican Republic team is grateful to M. Caram (PROFAMILIA) and M. Kelly (Laboratorio de Referencia) for contributions to the setup of the study platform. The CoronaVac vaccine was provided by the Brazilian government, and the ChAdOx1-S vaccine was provided by FioCruz Brazil.The Brazilian cohort setup team was supported by AstraZeneca externally sponsored scientific research program. A.I. and N.D.G. are recipients of the Fast Grant from Emergent Ventures at the Mercatus Center. N.D.G. and C.L. were supported by the Centers for Disease Control and Prevention Broad Agency Announcement Contract 75D30122C14697. A.I. was supported by the Women’s Health Research at Yale Pilot Project Program, Mathers Foundation, the Ludwig Family Foundation, the Department of Internal Medicine at the Yale School of Medicine, Yale School of Public Health, the Beatrice Kleinberg Neuwirth Fund, and the Howard Hughes Medical Institute. V.S.M. was supported by the CAPES-YALE fellowship.
Publisher Copyright:
Copyright © 2023 The Authors.
PY - 2023/2/15
Y1 - 2023/2/15
N2 - The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2–related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.
AB - The emergence of the SARS-CoV-2 Omicron sublineages resulted in increased transmission rates and reduced protection from vaccines. To counteract these effects, multiple booster strategies were used in different countries, although data comparing their efficiency in improving protective immunity remain sparse, especially among vulnerable populations, including older adults. The inactivated CoronaVac vaccine was among the most widely distributed vaccine worldwide and was essential in the early control of SARS-CoV-2–related hospitalizations and deaths. However, it is not well understood whether homologous versus heterologous booster doses in those fully vaccinated with CoronaVac induce distinct humoral responses or whether these responses vary across age groups. We analyzed plasma antibody responses from CoronaVac-vaccinated younger or older individuals who received a homologous CoronaVac or heterologous BNT162b2 or ChAdOx1 booster vaccine. All three evaluated boosters resulted in increased virus-specific IgG titers 28 days after the booster dose. However, we found that both IgG titers against SARS-CoV-2 Spike or RBD and neutralization titers against Omicron sublineages were substantially reduced in participants who received homologous CoronaVac compared with the heterologous BNT162b2 or ChAdOx1 booster. This effect was specifically prominent in recipients >50 years of age. In this group, the CoronaVac booster induced low virus-specific IgG titers and failed to elevate neutralization titers against any Omicron sublineage. Our results point to the notable inefficiency of CoronaVac immunization and boosting in mounting protective antiviral humoral immunity, particularly among older adults, during the Omicron wave. These observations also point to benefits of heterologous regimens in high-risk populations fully vaccinated with CoronaVac.
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UR - http://www.scopus.com/inward/citedby.url?scp=85152437353&partnerID=8YFLogxK
U2 - 10.1126/scitranslmed.ade6023
DO - 10.1126/scitranslmed.ade6023
M3 - Article
C2 - 36791210
AN - SCOPUS:85152437353
SN - 1946-6234
VL - 15
JO - Science translational medicine
JF - Science translational medicine
IS - 683
M1 - eade6023
ER -