Differences in transcriptional response underlie why prior vaccination exceeds prior infection in eliciting robust immune responses in Omicron infected outpatients

Abstract

The antibody response following Omicron infection has been reported to be less robust than to other variants. Here we compared the immune-transcriptome and antibody responses following Omicron infection in unvaccinated and vaccinated individuals who experienced mild to moderate symptoms. The unvaccinated individuals showed a quantitatively greater transcriptional response but a muted antibody response than vaccinated individuals. Prior vaccination modifies the transcriptional response to Omicron infection with a more robust antibody response.

Limited cross-variant immune response from SARS-CoV-2 Omicron BA.2 in naïve but not previously infected outpatients

“…While the Omicron BA.1 and BA.2 sublineages share mutations they also carry unique mutations, 28 in BA.2, which can explain their differential response to vaccine-induced and therapeutic antibodies (Ai et al, 2022; Arora et al, 2022a; Arora et al, 2022b). Previous studies have also demonstrated that BA.1 infection of naïve persons yields a very limited antibody response to SARS-CoV-2 VOCs other than Omicron itself (Lee et al ., 2022b; Rössler et al, 2022). However, prior vaccination or prior infection with older SARS-CoV-2 variants augment the immune response upon BA.1 breakthrough infection (Lee et al ., 2022b; Rössler et al ., 2022).…”

“…Previous studies have also demonstrated that BA.1 infection of naïve persons yields a very limited antibody response to SARS-CoV-2 VOCs other than Omicron itself (Lee et al, 2022b;Rössler et al, 2022). However, prior vaccination or prior infection with older SARS-CoV-2 variants augment the immune response upon BA.1 breakthrough infection (Lee et al, 2022b;Rössler et al, 2022). Our study now reveals that in antigen naïve individuals the immunologic response following BA.2 infection is even lower than that elicited by BA.1 infection as indicated by significantly lower antibody titers against all VOCs.…”

“…Previous studies have also demonstrated that BA.1 infection of naïve persons yields a very limited antibody response to SARS-CoV-2 VOCs other than Omicron itself (Lee et al, 2022b;Rössler et al, 2022). However, prior vaccination or prior infection with older SARS-CoV-2 variants augment the immune response upon BA.1 breakthrough infection (Lee et al, 2022b;Rössler et al, 2022).…”

“…Of note, vaccinated individuals with BA.1 infection develop measurable neutralizing antibody titers against BA.1 and BA.2 (Yu et al, 2022). Prior vaccination also broadens the immunological response against variants of concern (VOC) following Omicron infection whereas unvaccinated individuals show an antibody response more limited to the infecting strain (Lee et al, 2022b; Suryawanshi et al, 2022).…”

“…The ability of BA.2 infection to induce neutralizing antibodies in unvaccinated individuals, either without or with previous SARS-CoV-2 infection, is pending definition. Here we conducted a comparative investigation of the innate and humoral immune response elicited in 74 Omicron outpatients infected with BA.1 (Lee et al ., 2022b) or BA.2 that were either naïve prior to Omicron infection or had prior exposure to other SARS-CoV-2 variants. We measured antibody titers and ACE2 binding inhibition as a proxy to neutralization.…”