Humoral immune response to omicron infection in long-term Wuhan-Hu-1-imprinted population (preprint)

Recent WHO vaccination guidance no longer recommends COVID-19 vaccination beyond the first booster in low risk population, citing high population-level hybrid immunity due to widespread omicron infections.1 Although SARS-CoV-2 infection confers durable protection against reinfection,2-4 it may also produce immune imprinting, which skews subsequent immune response to variant antigens toward the first-exposed antigen based on the antigenic distance.5,6 China has the earliest and exclusively Wuhan-Hu-1(WH1)-imprinted population before the 2022 nation-wide omicron outbreak,7 which offers a unique opportunity to study long-term immune imprinting between most antigenically distant strains. Here, we assessed pseudovirus neutralization activity and anti-WH1 receptor binding domain (RBD) antibodies in 4 Chinese cohorts with hybrid or vaccine-only imprinting, or naïve to SARS-CoV-2 prior to omicron BF.7 infection. Both hybrid and vaccine-only imprinting augmented post-infection serum neutralization of WH1 and omicron sub-variants BF.7/BQ.1.1/XBB.1.5 comparing to naïve background. Feedback from pre-existing high-affinity antibodies limited the magnitude of humoral immune response to omicron infection without compromising protection, while antigenic seniority of pre-existing cross-reactive B cells only slightly reduces forward neutralization breadth in hybrid- and RBD vaccine-imprinted participants. Our results support the effectiveness of hybrid immunity against omicron reinfection in long-term imprinted population and provide immunological basis for similar epidemiological findings.8-10

Iontophoresis-Driven Microneedles Patch for Active Transdermal Delivery of Vaccine Macromolecules (preprint)

COVID-19 has seriously threatened public health and transdermal vaccination is an effective way to prevent pathogen infection. Microneedles (MN) can damage the stratum corneum for passive diffusion of vaccine macromolecules but the delivery efficiency is low, while iontophoresis can actively promote transdermal delivery but fails to transport vaccine macromolecules due to the barrier of stratum corneum. Herein, we developed a wearable iontophoresis-driven MN patch and its iontophoresis-driven device for active and efficient transdermal vaccine macromolecules delivery. Polyacrylamide/chitosan hydrogels with good biocompatibility, excellent conductivity, high elasticity and large loading capacity were prepared as the key component for vaccine storage and active iontophoresis. The transdermal vaccine delivery strategy of the iontophoresis-driven MN patch is: “press and poke, iontophoresis-driven delivery, and immune response”. We demonstrated that the synergistic effect of MN puncture and iontophoresis could significantly promote the transdermal vaccine delivery efficiency. In vitro experiments showed that the transdermal delivery amount of ovalbumin using iontophoresis-driven MN patch could be controlled by the iontophoresis current. In vivo immunization studies of Balb/c mice demonstrated that transdermal inoculation of ovalbumin using iontophoresis-driven MN patch induced an effective immune response, which was even stronger than that traditional intramuscular injection. Moreover, the iontophoresis-driven MN patch had little biosafety concern. This delivery system is low-cost, user-friendly, and active delivery that shows a great potential in vaccine self-administration at home.