Characterization of immune responses in fully vaccinated individuals after breakthrough infection with the SARS-CoV-2 delta variant

Abstract

Breakthrough infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants have been reported frequently in vaccinated individuals with waning immunity. In particular, a cluster of over 1,000 infections with the SARS-CoV-2 delta variant was identified in a predominantly fully vaccinated population in Provincetown, Massachusetts in July 2021. In this study, vaccinated individuals who tested positive for SARS-CoV-2 (n=16) demonstrated substantially higher serum antibody responses than vaccinated individuals who tested negative for SARS-CoV-2 (n=23), including 32-fold higher binding antibody titers and 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant. Vaccinated individuals who tested positive also showed higher mucosal antibody responses in nasal secretions and higher Spike protein-specific CD8 + T cell responses in peripheral blood than did vaccinated individuals who tested negative. These data demonstrate that fully vaccinated individuals developed robust anamnestic antibody and T cell responses following infection with the SARS-CoV-2 delta variant. Moreover, these findings suggest that population immunity will likely increase over time by a combination of widespread vaccination and breakthrough infections.

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

“…Mutations in the BA.1 S glycoprotein N-terminal domain (NTD) and RBD, which are the main targets of neutralizing antibodies (3,(11)(12)(13)(14)(15)(16), explain the markedly reduced plasma neutralizing activity of previously infected or vaccinated subjects, especially those that have not received booster doses, and escape from most monoclonal antibodies (mAbs) used in the clinic. As a result, an increasing number of reinfections or breakthrough infections are occurring (17)(18)(19), even though these cases tend to be milder than infections in immunologically naive individuals.…”

Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines

“…The emergence of the SARS-CoV-2 Delta and subsequently Omicron variants of concern led to an increasing number of reinfections and vaccine breakthrough cases ( 5, 41, 42 ). Public health policies were therefore updated worldwide to recommend administration of an additional vaccine dose (booster) several months after the primary vaccine series, which has been shown to increase the breadth and potency of neutralizing antibodies ( 5, 13 ).…”

Extensive neutralization against SARS-CoV-2 variants elicited by Omicron-specific subunit vaccine booster

“…In a study about the influenza vaccine, authors suggest that prior infection enhances antibody responses to inactivated vaccine and is important to attain protective antibody titers 27 . In the Delta breakthrough infection after fully vaccination, 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant than vaccinees without infection was observed 28 .…”

“…In a study about the influenza vaccine, authors suggest that prior infection enhances antibody responses to inactivated vaccine and is important to attain protective antibody titers 27 . In the Delta breakthrough infection after fully vaccination, 31-fold higher neutralizing antibody titers against the SARS-CoV-2 delta variant than vaccinees without infection was observed 28 . To evaluate the effect of prior vaccination on breakthrough infection, we analyzed the characteristics of humoral immune response elicited by Omicron variant after breakthrough infection.…”