Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.

We used plasma IgG proteomics to study the molecular composition and temporal durability of polyclonal IgG antibodies triggered by ancestral SARS-CoV-2 infection, vaccination, or their combination ("hybrid immunity"). Infection, whether primary or post-vaccination, mainly triggered an anti-spike antibody response to the S2 domain, while vaccination predominantly induced anti-RBD antibodies. Immunological imprinting persisted after a secondary (hybrid) exposure, with >60% of the ensuing serological response originating from the initial antibodies generated during the first exposure. We highlight one instance where hybrid immunity arising from breakthrough infection resulted in a marked increase in the breadth and affinity of a highly abundant vaccination-elicited plasma IgG antibody, SC27. With an intrinsic binding affinity surpassing a theoretical maximum (K D < 5 pM), SC27 demonstrated potent neutralization of various SARS-CoV-2 variants and SARS-like zoonotic viruses (IC 50 ∼0.1-1.75 nM) and provided robust protection in vivo . Cryo-EM structural analysis unveiled that SC27 binds to the RBD class 1/4 epitope, with both VH and VL significantly contributing to the binding interface. These findings suggest that exceptionally broad and potent antibodies can be prevalent in plasma and can largely dictate the nature of serological neutralization. HIGHLIGHTS: ▪ Infection and vaccination elicit unique IgG antibody profiles at the molecular level▪ Immunological imprinting varies between infection (S2/NTD) and vaccination (RBD)▪ Hybrid immunity maintains the imprint of first infection or first vaccination▪ Hybrid immune IgG plasma mAbs have superior neutralization potency and breadth.

Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination.

We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding domain (RBD) antibodies. This imprint persists after secondary exposures wherein >60% of ensuing hybrid immunity derives from the original IgG pool. Monoclonal constituents of the original IgG pool can increase breadth, affinity, and prevalence upon secondary exposures, as exemplified by the plasma antibody SC27. Following a breakthrough infection, vaccine-induced SC27 gained neutralization breadth and potency against SARS-CoV-2 variants and zoonotic viruses (half-maximal inhibitory concentration [IC50] ∼0.1-1.75 nM) and increased its binding affinity to the protective RBD class 1/4 epitope (dissociation constant [KD] < 5 pM). According to polyclonal escape analysis, SC27-like binding patterns are common in SARS-CoV-2 hybrid immunity. Our findings provide a detailed molecular definition of immunological imprinting and show that vaccination can produce class 1/4 (SC27-like) IgG antibodies circulating in the blood.

Same-Admission Microvascular Maxillofacial Ballistic Trauma Reconstruction Using Virtual Surgical Planning: A Case Series and Systematic Review.

Study Design: Retrospective case series; systematic review. Objective: It is unknown whether the use of virtual surgical planning (VSP) to facilitate same-admission microsurgical reconstruction of the mandible following acute maxillofacial ballistic trauma (MBT) is sufficient to achieve definitive reconstruction and functional occlusion. Methods: A single-center retrospective analysis was conducted for patients who underwent microsurgical reconstruction of the mandible using VSP after acute MBT. The PubMed/MEDLINE, Embase, ScienceDirect, and Scopus databases were systematically reviewed using blinded screening. Studies were evaluated via thematic analysis. Results: Five patients were treated by same-admission and microsurgical reconstruction of the mandible using VSP. We observed an average of 16.4 ± 9.1 days between initial presentation and reconstruction, an average length of stay of 51.6 ± 17.9 days, 6.2 ± 2.8 operations, and 1.6 ± 0.9 free flaps per patient. Four types and 8 total flaps were employed, most commonly the anterior lateral thigh flap (37.5%). Care yielded complete flap survival. Each patient experienced at least 1 minor complication. All patients achieved centric occlusion, oral nutrition, and an approximation of their baseline facial aesthetic. Follow up was 191.0 ± 183.9 weeks. Systematic review produced 8 articles that adhered to inclusion criteria. Consensus themes in the literature were found for clinical goal and function of VSP when practicing MBT reconstruction, yet disagreement was found surrounding optimal treatment timeline. Conclusions: Same-admission microsurgical reconstruction after MBT is safe and effective to re-establish mandibular form and function. VSP did not delay reconstruction, given the need for preparation prior to definitive reconstruction.

Acquired Sinus of Valsalva Fistula and Turner Syndrome.

A 21-year old woman with a history of Turner syndrome presented with a diastolic heart murmur, dizziness, dyspnea, and intermittent chest pain. Preoperative imaging revealed a fistula from the right sinus of Valsalva into the right atrium. Turner syndrome is associated with both aortopathy and congenital heart malformations. Acquired sinus of Valsalva fistula is a rare disorder, and this report describes its presence in association with Turner syndrome.