A boost with SARS-CoV-2 BNT162b2 mRNA vaccine elicits strong humoral responses independently of the interval between the first two doses

Abstract

SUMMARYDue to the recrudescence of SARS-CoV-2 infections worldwide, mainly caused by Omicron BA.1 and BA.2 variants of concern, several jurisdictions are administering a mRNA vaccine boost. Here, we analyzed humoral responses induced after the second and third doses of mRNA vaccine in naïve and previously-infected donors who received their second dose with an extended 16-week interval. We observed that the extended interval elicited robust humoral responses against VOCs, but this response was significantly diminished 4 months after the second dose. Administering a boost to these individuals brought back the humoral responses to the same levels obtained after the extended second dose. Interestingly, we observed that administering a boost to individuals that initially received a short 3-4 weeks regimen elicited humoral responses similar to those elicited in the long interval regimen. Nevertheless, humoral responses elicited by the boost in naïve individuals did not reach those present in previously-infected vaccinated individuals.

Humoral immune responses against SARS-CoV-2 Spike variants after mRNA vaccination in solid organ transplant recipients

“…We analyzed humoral immune responses in cohorts of 31 kidney, 11 liver, 14 lung and 8 heart organ transplant recipients after the second (median shown that this extended interval regimen leads to strong humoral and cellular responses after the second dose, notably against VOCs (Chatterjee et al, 2022;Nayrac et al, 2021;Payne et al, 2021;Tauzin et al, 2022a). This allowed us to compare humoral responses obtained in SOTR versus humoral responses elicited by a long interval vaccination regimen.…”

“…HCW received their first two doses of mRNA vaccine with a 16-week extended interval (median [range]: 111 days [76–134 days]), and their third dose around seven months after the second dose (median [range]: 219 days [167-235 days]), according to the province of Quebec, Canada public health authority’s vaccination roll out guidelines for HCW. Several studies have shown that this extended interval regimen leads to strong humoral and cellular responses after the second dose, notably against VOCs (Chatterjee et al, 2022; Nayrac et al, 2021; Payne et al, 2021; Tauzin et al, 2022a). This allowed us to compare humoral responses obtained in SOTR versus humoral responses elicited by a long interval vaccination regimen.…”

“…We also used a surrogate assay for antibody maturation by measuring the avidity for the RBD of vaccine-elicited Abs, using a previously described assay (Björkman et al, 1999;Fialová et al, 2017;Tauzin et al, 2022aTauzin et al, , 2022bTauzin et al, , 2022c. Briefly, plasma samples were tested in parallel by ELISA with washing steps having or not having a chaotropic agent (8M urea), measuring respectively the level of IgG with high avidity for the RBD and the level of total anti-RBD IgG.…”

“…Briefly, plasma samples were tested in parallel by ELISA with washing steps having or not having a chaotropic agent (8M urea), measuring respectively the level of IgG with high avidity for the RBD and the level of total anti-RBD IgG. The RBD-avidity index corresponds to the proportion of high avidity IgG among the total anti-RBD IgG (Figures 4), and provides an overall idea of antibody maturation (Björkman et al, 1999;Fialová et al, 2017;Tauzin et al, 2022aTauzin et al, , 2022bTauzin et al, , 2022c.…”

“…Because of the mutations, these VOCs are transmitted more efficiently than the original Wuhan strain and less well controlled by vaccination (Kumar et al, 2022; Lauring et al, 2022; Tseng et al, 2022). However, the administration of a third dose of mRNA vaccine (boost) leads to strong humoral responses and protects from severe outcome caused by these VOCs in the general population (Ariën et al, 2022; Tauzin et al, 2022a; Yoon et al, 2022). However, humoral responses elicited by the third dose on populations with compromised immune responses, particularly SOTR, are less documented.…”