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BACKGROUND. Maintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown. METHODS. We measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses. RESULTS. The booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months. CONCLUSION. The durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines., Introduction Recent studies have shown the declining efficacy of the Pfizer-BioNTech (BNT162b2) and Moderna (mRNA1273) mRNA vaccines after primary and booster vaccinations (1, 2). Although the booster vaccination (third dose) [...]

Authorization of the Matrix-M (MM)–adjuvanted R21 vaccine by three countries and its subsequent endorsement by the World Health Organization for malaria prevention in children are a milestone in the fight against malaria. Yet, our understanding of the innate and adaptive immune responses elicited by this vaccine remains limited. Here, we compared three clinically relevant adjuvants [3M-052 + aluminum hydroxide (Alum) (3M), a TLR7/8 agonist formulated in Alum; GLA-LSQ, a TLR4 agonist formulated in liposomes with QS-21; and MM, the now-approved adjuvant for R21] for their capacity to induce durable immune responses to R21 in macaques. R21 adjuvanted with 3M on a 0, 8, and 23–week schedule elicited anti-circumsporozoite antibody responses comparable in magnitude to the R21/MM vaccine administered using a 0-4-8–week regimen and persisted up to 72 weeks with a half-life of 337 days. A booster dose at 72 weeks induced a recall response similar to the R21/MM vaccination. In contrast, R21/GLA-LSQ immunization induced a lower, short-lived response at the dose used. Consistent with the durable serum antibody responses, MM and 3M induced long-lived plasma cells in the bone marrow and other tissues, including the spleen. Furthermore, whereas 3M stimulated potent and persistent antiviral transcriptional and cytokine signatures after primary and booster immunizations, MM induced enhanced expression of interferon- and TH2-related signatures more highly after the booster vaccination. Collectively, these findings provide a resource on the immune responses of three clinically relevant adjuvants with R21 and highlight the promise of 3M as another adjuvant for malarial vaccines. Editor's summary: Most vaccines based on recombinant antigens rely on coadministration with an adjuvant to elicit a robust immune response. Although adjuvants are needed for many vaccines, it is less clear which adjuvant(s) should be paired with each immunogen. In two papers, Bechtold et al. and Arunachalam et al. performed comparative analyses to assess the effect of different adjuvants on the immune response. Bechtold et al. showed that an AS01-adjuvanted hepatitis B virus vaccine, which induces robust CD4+ T cell responses against the vaccine antigen, also elicited trained immunity in human recipients, which was not observed in an alum-adjuvanted vaccine. Arunachalam et al. found that Matrix-M and 3M-052 + aluminum hydroxide (Alum) adjuvantation induced robust immune responses to the R21 malaria vaccine in nonhuman primates, but a third comparator, GLA-LSQ, elicited a lower magnitude of response that was short lived. Although Matrix-M and 3M-052 + Alum induced robust and durable antibody responses, they elicited distinct innate immune responses, demonstrating that multiple innate immune mechanisms can program durable vaccine-induced immunity. These head-to-head comparisons in both humans and nonhuman primates demonstrate that selecting an adjuvant should be done carefully and that different adjuvants have distinct effects on both innate and adaptive immunity. —Courtney Malo [ABSTRACT FROM AUTHOR]

Despite the growing body of research on urban tourism in the field of tourism and hospitality, only a limited number of studies have delved into the role of city breaks in tourism and analyzed the tourist experience in city break travel. The primary objective of this study is to identify and conceptualize city break tourism and provide guidance for contemporary analyses of city break travel experiences. Specifically, this study aims to: (1) identify the characteristics of city break travel and develop a conceptual framework for city break tourism based on these features; (2) explore the factors influencing city break tourist experiences. To achieve these goals, a systematic review of city breaks has been conducted in the tourism and hospitality sectors to gain a comprehensive understanding of city break tourism. The study contributes both theoretically and practically to the field. [ABSTRACT FROM AUTHOR]

Vaccine adjuvants increase the breadth of serum antibody responses, but whether this is due to the generation of antigen-specific B cell clones with distinct specificities or the maturation of memory B cell clones that produce broadly cross-reactive antibodies is unknown. Here, we longitudinally analyzed immune responses in healthy adults after two-dose vaccination with either a virus-like particle COVID-19 vaccine (CoVLP), CoVLP adjuvanted with AS03 (CoVLP+AS03), or a messenger RNA vaccination (mRNA-1273). CoVLP+AS03 enhanced the magnitude and durability of circulating antibodies and antigen-specific CD4+ T cell and memory B cell responses. Antigen-specific CD4+ T cells in the CoVLP+AS03 group at day 42 correlated with antigen-specific memory B cells at 6 months. CoVLP+AS03 induced memory B cell responses, which accumulated somatic hypermutations over 6 months, resulting in enhanced neutralization breadth of monoclonal antibodies. Furthermore, the fraction of broadly neutralizing antibodies encoded by memory B cells increased between day 42 and 6 months. These results indicate that AS03 enhances the antigenic breadth of B cell memory at the clonal level and induces progressive maturation of the B cell response. Editor's summary: Adjuvants are known to improve the magnitude, durability, and breadth of the immune response to vaccination, but how they modulate memory B cells is unclear. Grigoryan et al. analyzed immune responses in healthy individuals at multiple time points after two-dose vaccination with a plant-based SARS-CoV-2 vaccine (CoVLP) with or without adjuvant (AS03). AS03 adjuvant induced robust and more persistent RBD-specific memory B cells with increased neutralization breadth. This was due to AS03 promoting the selection of broadly neutralizing memory B cells, which accumulated SHMs over time. These findings highlight the role of adjuvants in enhancing memory B cell responses to vaccination. —Hannah Isles [ABSTRACT FROM AUTHOR]

Stable propagation of laser filamentation arrays paves new ways for cross‐scale manufacturing. Although a single filament or multiple filaments can be used for laser processing in transparent media, sustainable developments of higher throughput and lower energy consumption are always the pursuit. Here, a proof‐of‐concept approach is proposed in which cross‐scale manufacturing of 3D microstructures is realized via an ionization‐induced volume plasma grating. The volume plasma grating is generated by the noncollinear interaction of two batches of arrays of multiple filaments. The volume plasma grating cannot only regulate the distribution of multiple filamentation but also promote the intensity inside the filaments. By this approach, 3D microstructures are written by 1D sample translation. In addition, rapid fabrications of volume gratings and terahertz wire grid polarizers (THz WGPs) are demonstrated by laser modification using volume plasma grating. The characteristics of the fabricated THz WGPs are comparable to those of commercial ones. The limitations and future implementations of this approach are discussed. [ABSTRACT FROM AUTHOR]