Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines.
Nature
; 630(8018): 950-960, 2024 Jun.
Article
in En
| MEDLINE
| ID: mdl-38749479
ABSTRACT
Immune imprinting is a phenomenon in which prior antigenic experiences influence responses to subsequent infection or vaccination1,2. The effects of immune imprinting on serum antibody responses after boosting with variant-matched SARS-CoV-2 vaccines remain uncertain. Here we characterized the serum antibody responses after mRNA vaccine boosting of mice and human clinical trial participants. In mice, a single dose of a preclinical version of mRNA-1273 vaccine encoding Wuhan-1 spike protein minimally imprinted serum responses elicited by Omicron boosters, enabling generation of type-specific antibodies. However, imprinting was observed in mice receiving an Omicron booster after two priming doses of mRNA-1273, an effect that was mitigated by a second booster dose of Omicron vaccine. In both SARS-CoV-2-infected and uninfected humans who received two Omicron-matched boosters after two or more doses of the prototype mRNA-1273 vaccine, spike-binding and neutralizing serum antibodies cross-reacted with Omicron variants as well as more distantly related sarbecoviruses. Because serum neutralizing responses against Omicron strains and other sarbecoviruses were abrogated after pre-clearing with Wuhan-1 spike protein, antibodies induced by XBB.1.5 boosting in humans focus on conserved epitopes targeted by the antecedent mRNA-1273 primary series. Thus, the antibody response to Omicron-based boosters in humans is imprinted by immunizations with historical mRNA-1273 vaccines, but this outcome may be beneficial as it drives expansion of cross-neutralizing antibodies that inhibit infection of emerging SARS-CoV-2 variants and distantly related sarbecoviruses.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Immunization, Secondary
/
Antibodies, Neutralizing
/
COVID-19 Vaccines
/
SARS-CoV-2
/
COVID-19
/
MRNA Vaccines
/
Antibodies, Viral
Limits:
Adult
/
Animals
/
Female
/
Humans
/
Male
Country/Region as subject:
Asia
Language:
En
Journal:
Nature
Year:
2024
Document type:
Article
Affiliation country: