BNT162b2 booster after heterologous prime-boost vaccination induces potent neutralizing antibodies and T cell reactivity against SARS-CoV-2 Omicron BA.1 in young adults

Abstract

In light of the decreasing immune protection against symptomatic SARS-CoV-2 infection after initial vaccinations and the now dominant immune-evasive Omicron variants, ‘booster’ vaccinations are regularly performed to restore immune responses. Many individuals have received a primary heterologous prime-boost vaccination with long intervals between vaccinations, but the resulting long-term immunity and the effects of a subsequent ‘booster’, particularly against Omicron BA.1, have not been defined. We followed a cohort of 23 young adults, who received a primary heterologous ChAdOx1 nCoV-19 BNT162b2 prime-boost vaccination, over a 7-month period and analysed how they responded to a BNT162b2 ‘booster’. We show that already after the primary heterologous vaccination, neutralization titers against Omicron BA.1 are recognizable but that humoral and cellular immunity wanes over the course of half a year. Residual responsive memory T cells recognized spike epitopes of the early SARS-CoV-2 B.1 strain as well as the Delta and BA.1 variants of concern (VOCs). However, the remaining antibody titers hardly neutralized these VOCs. The ‘booster’ vaccination was well tolerated and elicited both high antibody titers and increased memory T cell responses against SARS-CoV-2 including BA.1. Strikingly, in this young heterologously vaccinated cohort the neutralizing activity after the ‘booster’ was almost as potent against BA.1 as against the early B.1 strain. Our results suggest that a ‘booster’ after heterologous vaccination results in effective immune maturation and potent protection against the Omicron BA.1 variant in young adults.

In-depth analysis of T cell immunity and antibody responses in heterologous prime-boost-boost vaccine regimens against SARS-CoV-2 and Omicron variant

“…Furthermore, in agreement with Beklitz et al, we showed decreased neutralizing capacities against Delta and Omicron in comparison to the SARS-CoV-2 WT (52). These observations are also in line with recent studies that demonstrated increased neutralizing antibody titers after first (prime-boost) (54) and second boost (prime-boost-boost) vaccination (39).…”

“…As a result of the SARS-CoV-2 pandemic, a considerable effort was made to investigate the safety and efficacy of newly generated vaccines. Recent studies have shown that heterologous and homologous prime-boost vaccine regimens result in adequate humoral and cellular immunity against SARS-CoV-2 ( 39 , 52 ), and prevent severe COVID-19 disease progression ( 53 ). Vaccines were initially developed against the ancestral SARS-CoV-2 Wuhan strain, and studies show that immunity against VOCs, especially Omicron, is equally achieved after the first ( 15 ) and second boost vaccination ( 47 ) of different vaccine regimens in terms of humoral immunity and rough T cell analysis ( 14 , 47 ).…”

“…Since COVID-19 vaccination is available and different vaccination strategies have been applied, the resulting immune response in different healthy and diseased cohorts has since been investigated (34,(39)(40)(41)(42)(43). However, further in-depth analysis of the humoral and cellular immune response can add to the existing knowledge, especially in light of the currently dominant Omicron variant.…”

Persistent T cell-mediated immune responses against Omicron variants after the third COVID-19 mRNA vaccine dose

“…Three months after the third vaccine dose, antibody levels decrease at a similar rate as after the second vaccine dose, while spike-speci c CD4 + and CD8 + T cells persist and effectively cross-recognize spike protein peptide pools from Omicron BA.1 and BA.2 variants. Our results support the ndings of other T cell studies on mRNA-vaccinated individuals 3,13,14 indicating a durable cell-mediated immunity against SARS-CoV-2.…”

What Proportion of Population has achieved Cellular Immunity against SARS-CoV-2 after Booster Vaccination: A Cross-sectional Study

“…Cellular immunity plays an important role in protecting individuals against severe cases of coronavirus disease 2019 (COVID-19), as reported in various studies, animal experiments [9,10], clinical studies [11,12,13,14,15,16,17,18,19,20], and general reviews [21,22,23]. Several studies showed booster vaccination induced stronger cellular immunity among relatively small number of participants or HCWs [24][25][26][27]. However, to this day, few studies have been conducted at the population level regarding cellular immunity after booster vaccination, and little is known about what proportion of population has achieved induced cellular immunity after booster vaccination and who is more likely to achieve it.…”