Longitudinal monitoring of mRNA-vaccine-induced immunity against SARS-CoV-2

Abstract

BackgroundWorldwide vaccination campaigns significantly reduced mortality caused by SARS-CoV-2 infection and diminished the devastating effects of the pandemic. The first approved vaccines are based on novel mRNA technology and elicit potent immune responses offering high levels of protection from severe disease.MethodsHere we longitudinally assessed adaptive immune responses during a 12-month follow-up period after the initial immunization with 2 doses of mRNA vaccines and after the booster dose in blood and saliva.ResultsOur findings demonstrate a rapid waning of the anti-spike IgG titers between months 3 and 6 after the initial vaccination (1.7- and 2.5-fold decrease in plasma and saliva, respectively; P<0.0001). Conversely, the frequency of spike-specific memory B cells increased during this period (2.4-fold increase; P<0.0001) while the frequency of spike-specific CD4+ and CD8+ T cells remained stable for all assessed functions: cytotoxicity, IFNγ, IL-2, and TNFα expression. Booster vaccination significantly improved the antibody response in plasma and saliva, with the most profound changes observed in the neutralization capacity against the currently circulating omicron variant (25.6-fold increase; P<0.0001). The positive effect of booster vaccination was also evident for spike-specific IgG+ memory B cell (2.4-fold increase; P<0.0001) and cytotoxic CD4+ and CD8+ T cell responses (1.7- and 1.9-fold increase respectively; P<0.05).ConclusionsCollectively, our findings offer a detailed insight into the kinetics of adaptive immune response following SARS-CoV-2 vaccination and underline the beneficial effects of a booster vaccination.

Long-Term SARS-CoV-2-Specific Humoral and T Cell Responses after the BNT162b2 or BBIBP-CorV Booster and the Incidence of Breakthrough Infections among Healthcare Workers

“…However, one year following the booster vaccination, the cumulative number of virus-specific T cells increased to a similar level to that measured two weeks after receiving the booster, and thus the T cell response remained quite stable up to one year following the third dose. These results are in line with the findings of other groups showing that in BNT162b2-primed individuals, the T cell-mediated response was similarly robust and well maintained for several months after either a BNT162b2 [16] or mRNA-1273 (Moderna, Cambridge, MA, USA) booster [19]. In a comparison of the homologous vaccination composed of three doses of the BNT162b2 vaccine and the heterologous vaccination utilizing two doses of AZD1222 (Oxford/AstraZeneca, Cambridge, UK) followed by a BNT162b2 booster, comparable results were also reported, as the T cell response remained vigorous and similar in both cohorts up to six months after the third vaccination [17].…”

Longitudinal Molecular and Serological Evidence of SARS-CoV-2 Infections and Vaccination Status: Community-Based Surveillance Study (CONTACT)

“…In patients who were IgG-positive at baseline, only 7 of 28 maintained detectable levels of IgG through 3-month and 6-month visits and had the first IgG-negative test after 9 months of follow up, with 14 of 28 without detectable levels of IgG by the 6-month visit. The rapid seroconversion rates from IgG-positive to IgG-negative found in some participants over 3 months in the absence of current infection are in line with previous findings that IgG response wanes quickly and that infection boosts IgG response [ 12 – 14 ].…”

Reprogramming human B cells with custom heavy-chain antibodies

“…45 Memory B cells may play an important role in immune responses in tissues, including the lung mucosa and solid tumors, 46,47 and can also re-seed the plasma cell compartment in response to repeat antigen exposure. 48,49 The antigen-responsiveness of memory B cells could be exploited to support the amplification and persistence of engineered B cells, or to tune the levels of antibodies that are produced.…”