Assessment of humoral and cellular immunity after bivalent BNT162b2 vaccination and potential association with reactogenicity

Abstract

Objectives This study investigated the feasibility and clinical value of using a novel, automated and high-throughput SARS-CoV-2 Interferon Gamma Release Assay (IGRA), combined with total anti-SARS-CoV-2 antibodies assessment, for evaluating the immune response after bivalent BNT162b2 vaccination. Methods A cohort of healthcare workers, who already underwent primary vaccination and boosting with monovalent BNT162b2 vaccine, received a booster dose of the new BNT162b2 bivalent formulation. Blood samples were taken immediately before vaccination (T0) and 1 month afterwards (T1). Humoral and cellular immunity were assayed with Roche Elecsys Anti-SARS-CoV-2 and Roche Elecsys IGRA SARS-CoV-2, respectively. Results The study population consisted of 51 subjects (median age: 43 years; 51% females). Total anti-SARS-CoV-2 antibodies and IGRA SARS-CoV-2 values increased at T1 from 9,050 to 25,000 BAU/mL (p<0.001), and from 0.44 to 0.78 IU/mL (p=0.385), accounting for median increase of 2.0 and 1.6 folds, respectively. Increased T1 values of total anti-SARS-CoV-2 antibodies and IGRA SARS-CoV-2 were recorded in 100% and 68.6% subjects, respectively. In those with baseline values below the median, post-vaccine levels displayed larger increases of 3.3 and 5.1 folds for anti-SARS-CoV-2 total antibodies and IGRA SARS-CoV-2, respectively. The variation of total anti-SARS-CoV-2 antibodies was inversely associated with their T0 values (r=−0.97; p<0.001), whilst that of IGRA SARS-CoV-2 was inversely associated with its T0 value (r=−0.58; p<0.001). No other signifcant associations were found with demographical or clinical variables, including side effects. Conclusions The bivalent BNT162b2 vaccine booster enhances humoral and cellular immunity against SARS-CoV-2, especially in recipients with lower baseline biological protection.

Humoral and cellular response three months following bivalent booster administration

“…Compared to Salvagno et al, the increase we observed was signi cant, although the p-value was close to 0.05 (i.e., p = 0.485). Our results agree with those of Salvagno et al on the fact that participants with lower cellular response at baseline were the ones who most bene t from a higher boost (3.3 and 2.9-fold increase after two weeks and one month in our studies, and 5.1-fold increase after one month according to Salvagno et al) (33).…”

“…The corresponding fold increase after the bivalent BA.4/5 booster was 1.4-1.7 and 1.9-2.6 (n = 18) and was therefore similar to that of the monovalent booster (34). In another study on 51 subjects, Salvagno et al identi ed a 1.8-fold increase in cellular response by means of an IFNγ release assay 1 month after the bivalent BA.4/5 booster, even if this increase was judged non-signi cant (33). The proportion of positive patients for IFNγ at baseline was 86.3% and increased at 98% 1 month afterwards.…”

“…The levels of binding antibodies were shown to signi cantly increase after the bivalent booster administration (33,34,36). The decrease of neutralizing antibodies was more rapid compared to the decrease of binding antibodies as illustrated by the striking difference in terms of T 1/2 observed in our study.…”

“…The IFNγ was then measured on the three tubes using the Elecsys IGRA SARS-CoV-2 test. Test results are standardized against the rst British IFNγ (human, leukocyte-derived) standard (NIBSC code 82/587) (33). The analyser calculates the IFNγ concentration in IU/mL and the limit of detection of the test is 0.07 IU/mL.…”

Clinical pearls and pitfalls of SARS-CoV-2 serology

“…Surrogate measures have hence been identified for mirroring the efficacy of the immune response, especially in individuals at higher likelihood of poor immunization (morbid, older, immunosuppressed), or in those at enhanced risk of risk of developing more severe more of illness [9] . The opportunity to assess both arms of the immune response by means of rapid, easy and relatively inexpensive laboratory tests (i.e., cellular immunity using interferon-γ release assay and humoral immunity with SARS-CoV-2 serology, respectively) [10] , is emerging as a valuable asset in both clinical practice and public health. To this end, early recognition of a blunted and or a faster decline of the immune response would enable to reliably identify individuals who may benefit most from additional or closer booster doses, as clearly shown by Achiron et al.…”