TY - JOUR
T1 - Fractionating a COVID-19 Ad5-vectored vaccine improves virus-specific immunity
AU - Sanchez, Sarah
AU - Palacio, Nicole
AU - Dangi, Tanushree
AU - Ciucci, Thomas
AU - Penaloza-MacMaster, Pablo
N1 - Publisher Copyright:
© 2021 The Authors.
PY - 2021/12
Y1 - 2021/12
N2 - SARS-CoV-2 has caused a global pandemic that has infected more than 250 million people worldwide. Although several vaccine candidates have received emergency use authorization, there is still limited knowledge on how vaccine dosing affects immune responses. We performed mechanistic studies in mice to understand how the priming dose of an adenovirus-based SARS-CoV-2 vaccine affects long-term immunity to SARS-CoV-2. We first primed C57BL/6 mice with an adenovirus serotype 5 vaccine encoding the SARS-CoV-2 spike protein, similar to that used in the CanSino and Sputnik V vaccines. The vaccine prime was administered at either a standard dose or 1000-fold lower dose, followed by a boost with the standard dose 4 weeks later. Initially, the low dose prime induced lower immune responses relative to the standard dose prime. However, the low dose prime elicited immune responses that were qualitatively superior and, upon boosting, exhibited substantially more potent recall and functional capacity. We also report similar effects with a simian immunodeficiency virus (SIV) vaccine. These findings show an unexpected advantage of fractionating vaccine prime doses, warranting a reevaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.
AB - SARS-CoV-2 has caused a global pandemic that has infected more than 250 million people worldwide. Although several vaccine candidates have received emergency use authorization, there is still limited knowledge on how vaccine dosing affects immune responses. We performed mechanistic studies in mice to understand how the priming dose of an adenovirus-based SARS-CoV-2 vaccine affects long-term immunity to SARS-CoV-2. We first primed C57BL/6 mice with an adenovirus serotype 5 vaccine encoding the SARS-CoV-2 spike protein, similar to that used in the CanSino and Sputnik V vaccines. The vaccine prime was administered at either a standard dose or 1000-fold lower dose, followed by a boost with the standard dose 4 weeks later. Initially, the low dose prime induced lower immune responses relative to the standard dose prime. However, the low dose prime elicited immune responses that were qualitatively superior and, upon boosting, exhibited substantially more potent recall and functional capacity. We also report similar effects with a simian immunodeficiency virus (SIV) vaccine. These findings show an unexpected advantage of fractionating vaccine prime doses, warranting a reevaluation of vaccine trial protocols for SARS-CoV-2 and other pathogens.
UR - http://www.scopus.com/inward/record.url?scp=85122131057&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85122131057&partnerID=8YFLogxK
U2 - 10.1126/sciimmunol.abi8635
DO - 10.1126/sciimmunol.abi8635
M3 - Article
C2 - 34648369
AN - SCOPUS:85122131057
SN - 2470-9468
VL - 6
JO - Science Immunology
JF - Science Immunology
IS - 66
M1 - abi8635
ER -