Phase 1, randomized, rater and participant blinded placebo-controlled study of the safety, reactogenicity, tolerability and immunogenicity of H1N1 influenza vaccine delivered by VX-103 (a MIMIX microneedle patch [MAP] system) in healthy adults.

BACKGROUND: The MIMIX platform is a novel microneedle array patch (MAP) characterized by slowly dissolving microneedle tips that deploy into the dermis following patch application. We describe safety, reactogenicity, tolerability and immunogenicity for MIMIX MAP vaccination against influenza. METHODOLOGY: The trial was a Phase 1, exploratory, first-in-human, parallel randomized, rater, participant, study analyst-blinded, placebo-controlled study in Canada. Forty-five healthy participants (18 to 39 years of age, inclusive) were randomized in a 1:1:1 ratio to receive either 15 µg or 7.5 µg of an H1N1 influenza vaccine, or placebo delivered via MIMIX MAP to the volar forearm. A statistician used a computer program to create a randomization scheme with a block size of 3. Post-treatment follow-up was approximately 180 days. Primary safety outcomes included the incidence of study product related serious adverse events and unsolicited events within 180 days, solicited application site and systemic reactogenicity through 7 days after administration and solicited application site erythema and/or pigmentation 14, 28, 56 and 180 days after administration. Immunogenicity outcomes included antibody titers and percentage of seroconversion (SCR) and seroprotection (SPR) rates determined by the hemagglutination inhibition (HAI) assay. Exploratory outcomes included virus microneutralization (MN) titers, durability and breadth of the immune response. The trial was registered with ClinicalTrials.gov, number NCT06125717. FINDINGS: Between July 7, 2022 and March 13, 2023 45 participants were randomized to a treatment group. One participant was lost to follow up in the 15 µg group and 1 participant withdrew from the 7.5 µg dose group. Safety analyses included n = 15 per group, immunogenicity analyses included n = 14 for the 15 µg and 7.5 µg treatment groups and n = 15 for the placebo group. No SAEs were reported in any of the treatment groups. All treatment groups reported solicited local events within 7 days after vaccination, with mild (Grade 1) erythema being the most frequent symptom reported. Other local symptoms reported included mostly mild (Grade 1) induration/swelling, itching, pigmentation, skin flaking, and tenderness. Within 7 days after vaccination, 2 participants (4.4%) reported moderate (Grade 2) erythema, 1 participant (2.2%) reported moderate (Grade 2) induration/swelling, and 1 participant (2.2%) reported moderate (Grade 2) itching. There was an overall reduction in erythema and pigmentation reported on Days 15, 29, 57, and 180 among all treatment groups. Systemic symptoms reported within 7 days after vaccination, included mild (Grade 1) fatigue reported among all treatment groups, and mild (Grade 1) headache reported by 1 participant in the 7.5 µg treatment group. No study drug related severe symptoms were reported in the study. Group mean fold rises in HAI titers ranged between 8.7 and 12-fold, SCRs were >76% and SPRs were >92% for both VX-103 dose groups thereby fulfilling serological criteria established by the EMA and FDA for seasonal influenza vaccines. Longitudinal assessments demonstrate persistence of the immune response through at least Day 180. CONCLUSIONS: The MIMIX MAP platform is safe, well tolerated and elicits robust antibody responses.

Trends in the administration of COVID-19 vaccines with other vaccines in the United States reported to V-safe during December 14, 2020-May 19, 2023.

Introduction COVID-19 vaccines may be administered with other vaccines during the same healthcare visit. COVID-19 monovalent (Fall 2021) and bivalent (Fall 2022) vaccine recommendations coincided with annual seasonal influenza vaccination. Data describing the frequency of the co-administration of COVID-19 vaccines with other vaccines are limited. Methods We used V-safe, a voluntary smartphone-based U.S. safety surveillance system established by the CDC, to describe trends in the administration of COVID-19 vaccines with other vaccines reported to V-safe during December 14, 2020 - May 19, 2023. Results Of the 21 million COVID-19 vaccinations reported to V-safe, 2.2% (459,817) were administered with at least 1 other vaccine. Co-administration most frequently occurred during the first week of October 2023 (27,092; 44.1%). Most reports of co-administration included influenza vaccine (393,003; 85.5%). Co-administration was most frequently reported for registrants aged 6 months-6 years (4,872; 4.4%). Conclusion Reports of co-administration to V-safe peaked during October 2023, when influenza vaccination most often occurs, possibly reflecting increased opportunities for multiple vaccinations and greater acceptability of the co-administration of COVID-19 vaccine with other vaccines, especially influenza vaccine.

Transdermal microarrayed electroporation for enhanced cancer immunotherapy based on DNA vaccination.

Despite the tremendous clinical potential of nucleic acid-based vaccines, their efficacy to induce therapeutic immune response has been limited by the lack of efficient local gene delivery techniques in the human body. In this study, we develop a hydrogel-based organic electronic device (µEPO) for both transdermal delivery of nucleic acids and in vivo microarrayed cell electroporation, which is specifically oriented toward one-step transfection of DNAs in subcutaneous antigen-presenting cells (APCs) for cancer immunotherapy. The µEPO device contains an array of microneedle-shaped electrodes with pre-encapsulated dry DNAs. Upon a pressurized contact with skin tissue, the electrodes are rehydrated, electrically triggered to release DNAs, and then electroporate nearby cells, which can achieve in vivo transfection of more than 50% of the cells in the epidermal and upper dermal layer. As a proof-of-concept, the µEPO technique is employed to facilitate transdermal delivery of neoantigen genes to activate antigen-specific immune response for enhanced cancer immunotherapy based on a DNA vaccination strategy. In an ovalbumin (OVA) cancer vaccine model, we show that high-efficiency transdermal transfection of APCs with OVA-DNAs induces robust cellular and humoral immune responses, including antigen presentation and generation of IFN-γ+ cytotoxic T lymphocytes with a more than 10-fold dose sparing over existing intramuscular injection (IM) approach, and effectively inhibits tumor growth in rodent animals.

Preparation and Study of Bacterins.

Streptococcus suis is a bacterial pathogen that can cause significant economic losses in the swine industry due to high morbidity and mortality rates in infected animals. Vaccination with bacterins, which consist of inactivated bacteria and adjuvants to enhance the pig's immune response, is an effective approach to control S. suis infections in piglets. Here we provide a description of S. suis bacterins and the methods for vaccine preparation. Moreover, this chapter also describes the addition of recombinant Sao (rSao-L) protein to the S. suis bacterin, aiming to enhance the efficacy of the bacterins against S. suis in piglets. Furthermore, the methods for evaluating the immune response elicited by the bacterins are also covered in this chapter.

Treatment and Vaccination for Smallpox and Monkeypox.

The smallpox infection with the variola virus was one of the most fatal disorders until a global eradication was initiated in the twentieth century. The last cases were reported in Somalia 1977 and as a laboratory infection in the UK 1978; in 1980, the World Health Organization (WHO) declared smallpox for extinct. The smallpox virus with its very high transmissibility and mortality is still a major biothreat, because the vaccination against smallpox was stopped globally in the 1980s. For this reason, new antivirals (cidofovir, brincidofovir, and tecovirimat) and new vaccines (ACAM2000, LC16m8 and Modified Vaccine Ankara MVA) were developed. For passive immunization, vaccinia immune globulin intravenous (VIGIV) is available. Due to the relationships between orthopox viruses such as vaccinia, variola, mpox (monkeypox), cowpox, and horsepox, the vaccines (LC16m8 and MVA) and antivirals (brincidofovir and tecovirimat) could also be used in the mpox outbreak with positive preliminary data. As mutations can result in drug resistance against cidofovir or tecovirimat, there is need for further research. Further antivirals (NIOCH-14 and ST-357) and vaccines (VACΔ6 and TNX-801) are being developed in Russia and the USA. In conclusion, further research for treatment and prevention of orthopox infections is needed and is already in progress. After a brief introduction, this chapter presents the smallpox and mpox disease and thereafter full overviews on antiviral treatment and vaccination including the passive immunization with vaccinia immunoglobulins.

Modulation of innate immune response to mRNA vaccination after SARS-CoV-2 infection or sequential vaccination in humans.

mRNA vaccines are likely to become widely used for the prevention of infectious diseases in the future. Nevertheless, a notable gap exists in mechanistic data, particularly concerning the potential effects of sequential mRNA immunization or preexisting immunity on the early innate immune response triggered by vaccination. In this study, healthy adults, with or without documented prior SARS-CoV-2 infection, were vaccinated with the BNT162b2/Comirnaty mRNA vaccine. Prior infection conferred significantly stronger induction of proinflammatory and type I IFN-related gene signatures, serum cytokines, and monocyte expansion after the prime vaccination. The response to the second vaccination further increased the magnitude of the early innate response in both study groups. The third vaccination did not further increase vaccine-induced inflammation. In vitro stimulation of PBMCs with TLR ligands showed no difference in cytokine responses between groups, or before or after prime vaccination, indicating absence of a trained immunity effect. We observed that levels of preexisting antigen-specific CD4 T cells, antibody, and memory B cells correlated with elements of the early innate response to the first vaccination. Our data thereby indicate that preexisting memory formed by infection may augment the innate immune activation induced by mRNA vaccines.

Immune responses associated with protection induced by chemoattenuated PfSPZ vaccine in malaria-naive Europeans.

Vaccination of malaria-naive volunteers with a high dose of Plasmodium falciparum sporozoites chemoattenuated by chloroquine (CQ) (PfSPZ-CVac [CQ]) has previously demonstrated full protection against controlled human malaria infection (CHMI). However, lower doses of PfSPZ-CVac [CQ] resulted in incomplete protection. This provides the opportunity to understand the immune mechanisms needed for better vaccine-induced protection by comparing individuals who were protected with those not protected. Using mass cytometry, we characterized immune cell composition and responses of malaria-naive European volunteers who received either lower doses of PfSPZ-CVac [CQ], resulting in 50% protection irrespective of the dose, or a placebo vaccination, with everyone becoming infected following CHMI. Clusters of CD4+ and γδ T cells associated with protection were identified, consistent with their known role in malaria immunity. Additionally, EMRA CD8+ T cells and CD56+CD8+ T cell clusters were associated with protection. In a cohort from a malaria-endemic area in Gabon, these CD8+ T cell clusters were also associated with parasitemia control in individuals with lifelong exposure to malaria. Upon stimulation with P. falciparum-infected erythrocytes, CD4+, γδ, and EMRA CD8+ T cells produced IFN-γ and/or TNF, indicating their ability to mediate responses that eliminate malaria parasites.

Predicting vaccine effectiveness for mpox.

The Modified Vaccinia Ankara vaccine developed by Bavarian Nordic (MVA-BN) was widely deployed to prevent mpox during the 2022 global outbreak. This vaccine was initially approved for mpox based on its reported immunogenicity (from phase I/II trials) and effectiveness in animal models, rather than evidence of clinical efficacy. However, no validated correlate of protection after vaccination has been identified. Here we performed a systematic search and meta-analysis of the available data to test whether vaccinia-binding ELISA endpoint titer is predictive of vaccine effectiveness against mpox. We observe a significant correlation between vaccine effectiveness and vaccinia-binding antibody titers, consistent with the existing assumption that antibody levels may be a correlate of protection. Combining this data with analysis of antibody kinetics after vaccination, we predict the durability of protection after vaccination and the impact of dose spacing. We find that delaying the second dose of MVA-BN vaccination will provide more durable protection and may be optimal in an outbreak with limited vaccine stock. Although further work is required to validate this correlate, this study provides a quantitative evidence-based approach for using antibody measurements to predict the effectiveness of mpox vaccination.

Antibody persistence and revaccination recommendations of MenACWY-TT: a review of clinical studies assessing antibody persistence up to 10 years after vaccination.

INTRODUCTION: Invasive meningococcal disease (IMD) is potentially fatal and associated with severe sequelae among survivors. It is preventable by several vaccines, including meningococcal vaccines targeting the most common disease-causing serogroups (A, B, C, W, Y). The meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT [Nimenrix]) is indicated from 6 weeks of age in the European Union and >50 additional countries. AREAS COVERED: Using PubMed, Google Scholar, ClinicalTrials.gov and ad hoc searches for publications to June 2023, we review evidence of antibody persistence for up to 10 years after primary vaccination and up to 6 years after MenACWY-TT revaccination. We also review global MenACWY revaccination recommendations and real-world impact of vaccination policies, focusing on how these data can be considered alongside antibody persistence data to inform future IMD prevention strategies. EXPERT OPINION: Based on clear evidence that immunogenicity data (demonstrated antibody titers above established correlates of protection) are correlated with real-world effectiveness, long-term persistence of antibodies after MenACWY-TT vaccination suggests continuing protection against IMD. Optimal timing of primary and subsequent vaccinations is critical to maximize direct and indirect protection. Recommending bodies should carefully consider factors such as age at vaccination and long-term immune responses associated with the specific vaccine being used.

Immunogenicity and safety of a recombinant Omicron BA.4/5-Delta COVID-19 vaccine ZF2202-A in Chinese adults.

BACKGROUND: The Recombinant Omicron BA.4/5-Delta COVID-19 Vaccine (ZF2202-A) is primarily designed for the Delta and Omicron BA.4/5 variants. Our objective was to assess the safety and immunogenicity of ZF2202-A in Chinese adults. METHODS: A total of 450 participants aged ≥ 18 years, who had completed primary or booster vaccination with a COVID-19 vaccine more than 6 months prior, were enrolled in this randomized, double-blind, active-controlled trial. Participants in the study and control groups were administered one dose of ZF2202-A and ZF2001, respectively. Immunogenicity subgroups were established in each group. RESULTS: At 14 days after vaccination, the seroconversion rates of Omicron BA.4/5, BF.7, and XBB.1 in the ZF2022-A group were 67.7 %, 58.6 %, and 62.6 %, with geometric mean titers (GMTs) of neutralizing antibodies at 350.2, 491.8, and 49.5, respectively. The main adverse reactions (ARs) were vaccination site pain, pruritus, fatigue, and asthenia in both the ZF2022-A group and ZF2001 group. CONCLUSIONS: The novel bivalent vaccine ZF2202-A demonstrated satisfactory immunogenicity and safety against Omicron variants as booster dose in adults with prior vaccination of COVID-19 vaccines.

Lipid nanoparticle composition for adjuvant formulation modulates disease after influenza virus infection in quadrivalent influenza vaccine vaccinated mice.

There are considerable avenues through which currently licensed influenza vaccines could be optimized. We tested influenza vaccination in a mouse model with two adjuvants: Sendai virus-derived defective interfering (SDI) RNA, a RIG-I agonist; and an amphiphilic imidazoquinoline (IMDQ-PEG-Chol), a TLR7/8 agonist. The negatively charged SDI RNA was formulated into lipid nanoparticles (LNPs) facilitating direct delivery of SDI RNA to the cytosol, where RIG-I sensing induces inflammatory and type I interferon responses. We previously tested SDI RNA and IMDQ-PEG-Chol as standalone and combination adjuvants for influenza and SARS-CoV-2 vaccines. Here, we tested two different ionizable lipids, K-Ac7-Dsa and S-Ac7-Dog, for LNP formulations. The LNPs were incorporated with SDI RNA to determine its potential as a combination adjuvant with IMDQ-PEG-Chol by evaluating the host immune response to vaccination and infection in immunized BALB/c mice. Adjuvanticity of IMDQ-PEG-Chol with and without empty or SDI-loaded LNPs was validated with quadrivalent inactivated influenza vaccine (QIV), showing robust induction of antibody titers and T-cell responses. Depending on the adjuvant combination and LNP formulation, humoral and cellular vaccine responses could be tailored towards type 1 or type 2 host responses with specific cytokine profiles that correlated with the protective responses to viral infection. The extent of protection conferred by different vaccine/LNP/adjuvant combinations was tested by challenging mice with a vaccine-matched strain of influenza A virus A/Singapore/gp1908/2015 IVR-180 (H1N1). Groups that received either LNP formulated with SDI or IMDQ-PEG-Chol, or both, showed very low levels of viral replication in their lungs at 5 days post-infection (DPI). These studies provide evidence that the combination of vaccines with LNPs and/or adjuvants promote antigen-specific cellular responses that can contribute to protection upon infection. Interestingly, we observed differences in humoral and cellular responses to vaccination between different groups receiving K-Ac7-Dsa or S-Ac7-Dog lipids in LNP formulations. The differences were also reflected in inflammatory responses in lungs of vaccinated animals to infection, depending on LNP formulations. Therefore, this study suggests that the composition of the LNPs, particularly the ionizable lipid, plays an important role in inducing inflammatory responses in vivo, which is important for vaccine safety and to prevent adverse effects upon viral exposure.

The impact and cost-effectiveness of pneumococcal immunisation strategies for the elderly in England.

Pneumococcal disease, presenting as invasive pneumococcal disease (IPD) or community-acquired pneumonia (CAP) is an important cause of illness and hospitalisation in the elderly. To reduce pneumococcal burden, since 2003, 65-year-olds in England have been offered a 23-valent pneumococcal polysaccharide vaccine (PPV23). This study compares the impact and cost-effectiveness (CE) of vaccination with the existing PPV23 vaccine to the new 15-and 20-valent pneumococcal conjugate vaccines (PCV15 and PCV20), targeting adults aged 65 or 75 years old. We developed a static Markov model for immunisation against pneumococcal disease, capturing different vaccine effectiveness and immunity waning assumptions, projecting the number of IPD/CAP cases averted over the thirty years following vaccination. Using an economic model and probabilistic sensitivity analysis we evaluated the CE of the different immunisation strategies at current vaccine list prices and the willingness-to-pay at a median threshold of £20,000/QALY and an uncertainty threshold of 90% of simulations below £30,000/QALY. PCV20 averted more IPD and CAP cases than PCV15 or PPV23 over the thirty years following vaccination: 353(360), 145(159) and 150(174) IPD and 581(673), 259(485) and 212(235) CAP cases at a vaccination age of 65(75) under base vaccine effectiveness assumptions. At the listed prices of PCV20 and PPV23 vaccines as of May 2023, both vaccines were cost-effective when vaccinating 65- or 75-year-olds with an ICER threshold of £20,000 per QALY. To achieve the same cost-effectiveness as PPV23, the additional cost of PCV20 should be less than £44(£91) at an ICER threshold of £20,000/QALY (£30,000/QALY) if vaccination age is 65 (or £54(£103) if vaccination age is increased to 75). We showed that both PPV23 and PCV20 were likely to be cost-effective. PCV20 was likely to avert more cases of pneumococcal disease in elderly adults in England than the current PPV23 vaccine, given input assumptions of a higher vaccine effectiveness and slower waning for PCV20.

Report from the World Health Organization's immunization and vaccines-related implementation research advisory committee (IVIR-AC) meeting, virtual gathering, 26 February-1 March 2024.

The Immunization and Vaccine-related Implementation Research Advisory Committee (IVIR-AC) is the World Health Organization's key standing advisory body to conduct an independent review of research, particularly of transmission and economic modeling analyses that estimate the impact and value of vaccines. From 26th February-1st March 2024, at its first of two semi-annual meetings, IVIR-AC provided feedback and recommendations across four sessions; this report summarizes the proceedings and recommendations from that meeting. Session topics included modeling of the impact and cost-effectiveness of the R21/Matrix-M malaria vaccine, meta-analysis of economic evaluations of vaccines, a global analysis estimating the impact of vaccination over the last 50 years, and modeling the impact of different RTS,S malaria vaccine dose schedules in seasonal settings.

Functional antibody responses targeting the Spike protein of SARS-CoV-2 Omicron XBB.1.5 in elderly nursing home residents following Wuhan-Hu-1-based mRNA booster vaccination.

The immune effector mechanisms involved in protecting against severe COVID-19 infection in elderly nursing home residents following vaccination or natural infection are not well understood. Here, we measured SARS-CoV-2 Spike (S)-directed functional antibody responses, including neutralizing antibodies (NtAb) and antibody Fc-mediated NK cell activity (degranulation and IFNγ production), against the Wuhan-Hu-1, BA.4/5 (for NtAb), and Omicron XBB.1.5 variants in elderly nursing home residents (n = 39; median age, 91 years) before and following a third (pre- and post-3D) and a fourth (pre- and post-4D) mRNA COVID-19 vaccine dose. Both 3D and 4D boosted NtAb levels against both (sub)variants. Likewise, 3D and 4D increased the ability of sera to trigger both LAMP1- and IFNγ-producing NK cells, in particular against XBB.1.5. In contrast to NtAb titres, the frequencies of LAMP1- and IFNγ-producing NK cells activated by antibodies binding to Wuhan-Hu-1 and Omicron XBB.1.5 S were comparable at all testing times. Stronger functional antibody responses were observed in vaccine-experienced participants compared to vaccine-naïve at some testing times. These findings can contribute to identifying a reliable correlate of protection in elderly nursing home residents against severe COVID-19 and inform future vaccine strategies in this population group.

Effectiveness of cocoon strategy vaccination on prevention of influenza-like illness in young infants.

During the initial half-year of their existence, infants cannot receive the influenza vaccine, yet they face the greatest susceptibility to severe influenza complications. In this study, we seek to determine whether influenza vaccination of maternal and household contacts is associated with a reduced risk of influenza-like illness (ILI) and severe acute respiratory infection (SARI) in infants. This work was prospectively conducted during the influenza season. A total of 206 infants were included in this study. The percentage of infants with only the mother vaccinated is 12.6% (n:26), and the percent of infants with all household contacts vaccinated is 16% (n:33). Among the infants with only the mother vaccinated, the effectiveness of influenza vaccine is estimated as 35.3% for ILI and 41.3% for SARI. Among infants with all household contacts vaccinated, the effectiveness is estimated as 48.9% for ILI and 76.9% for SARI. Based on the results of multivariate logistic regression analysis, all-household vaccination is a protective factor against SARI (OR: 0.07 95% CI [0.01-0.56]), household size (OR: 1.75, 95% CI [1.24-2.48]) and presence of secondhand smoke (OR: 2.2, 95% CI [1.12-4.45]) significant risk factors for SARI in infants. The mother alone being vaccinated is not a statistically significant protective factor against ILI (OR: 0.46, 95% CI [0.19-1.18]) or SARI (OR: 0.3, 95% CI [0.11-1.21]). Along with the obtained results and analysis, this study provides clear evidence that influenza vaccination of all household contacts of infants aged 0-6 months is significantly associated with protecting infants from both ILI and SARI.

Effectiveness of a School- and Primary Care-Based HPV Vaccination Intervention: The PrevHPV Cluster Randomized Trial.

Importance: The human papillomavirus (HPV) vaccine is safe and effective, yet vaccination coverage remains below public health objectives in many countries. Objective: To examine the effectiveness of a 3-component intervention on HPV vaccination coverage among adolescents aged 11 to 14 years 2 months after the intervention ended, each component being applied alone or in combination. Design, Setting, and Participants: A cluster randomized trial with incomplete factorial design (PrevHPV) was conducted between July 1, 2021, and April 30, 2022, in French municipalities receiving 0, 1, 2, or 3 components of the intervention. Randomization was stratified by school district and municipalities' socioeconomic level. Analyses were carried out on 11- to 14-year-old adolescents living in all participating municipalities, regardless of what had been implemented. Intervention: The PrevHPV intervention had 3 components: (1) educating and motivating 11- to 14-year-old adolescents in middle schools, along with their parents; (2) training general practitioners (GPs) on up-to-date HPV information and motivational interviewing techniques; and (3) free HPV vaccination at school. Main Outcomes and Measures: The primary outcome was HPV vaccination coverage (≥1 dose) 2 months after the intervention ended among 11- to 14-year-old adolescents living in participating municipalities, based on the French national reimbursement database and data collected during the trial in groups randomized to implement at-school vaccination. Results: A total of 91 municipalities comprising 30 739 adolescents aged 11 to 14 years (15 876 boys and 14 863 girls) were included and analyzed. Half the municipalities were in the 2 lowest socioeconomic quintiles and access to GPs was poor in more than two-thirds of the municipalities. Thirty-eight of 61 schools (62.3%) implemented actions and 26 of 45 municipalities (57.8%) had at least 1 trained GP. The median vaccination coverage increased by 4.0 percentage points (IQR, 2.0-7.3 percentage points) to 14.2 percentage points (IQR, 9.1-17.3 percentage points) at 2 months. At-school vaccination significantly increased vaccination coverage (5.50 percentage points [95% CI, 3.13-7.88 percentage points]) while no effect was observed for adolescents' education and motivation (-0.08 percentage points [95% CI, -2.54 to 2.39 percentage points]) and GPs' training (-1.46 percentage points [95% CI, -3.44 to 0.53 percentage points]). Subgroup analyses found a significant interaction between at-school vaccination and access to GPs, with a higher effect when access was poor (8.62 percentage points [95% CI, 5.37-11.86 percentage points] vs 2.13 percentage points [95% CI, -1.25 to 5.50 percentage points]; P = .007 for interaction). Conclusions and Relevance: In this cluster randomized trial, within the context of the late COVID-19 pandemic period and limited school and GP participation, at-school HPV vaccination significantly increased vaccination coverage. The trial did not show a significant effect for training GPs and education and motivation, although it may be observed after more time has elapsed after the intervention. Trial Registration: ClinicalTrials.gov Identifier: NCT04945655.

PMMA dialyzers modulate both humoral and cell-mediate immune response to anti-COVID-19 vaccine (BNT162b2) in a cohort of chronic hemodialyzed patients.

Patients on hemodialysis (HD) have a high risk of death from COVID-19. We evaluated the humoral and cell-mediated immune response to BNT162b2 (Pfizer-BioNTech) vaccine in HD patients, comparing HD with Poly-methyl-methacrylate (PMMA) and HD with Polysulphone (PS). Samples were collected before vaccination (T0) and 14-days after the 2ndvaccine (T2) in a TG (TG, n = 16-Foggia) and in a VG (CG, n = 36-Novara). Anti-SARS-CoV-2-Ig were titrated in the cohort 2-weeks after the 2nddose of vaccine. In the Testing-Group, serum neutralizing antibodies (NAb) were assayed and PBMCs isolated from patients were thawed, counted and stimulated with SARS-CoV-2 IGRA stimulation tube set. All patients had a positive ab-response, except in a case. PMMA-patients had higher levels of anti-SARS-CoV-2 IgG (p = 0.031); VG data confirmed these findings (p < 0.05). NAb evaluation: PMMA patients passed the positive cut-off value, while in PS group only only 1/8 patient did not respond. PMMA patients showed higher percentages of anti-SARS-CoV-2 S1/RBD-Ig after a complete vaccine schedule (p = 0.028). Interferon-gamma release: PMMA patients showed significantly higher release of IFNγ (p = 0.014). The full vaccination course provided sufficient protection against SARS-CoV-2 across the entire cohort, regardless of dialyzer type. After vaccination, PMMA patients show a better immune response, both humoral and cellular, at the end of the vaccination course than PS patients.

Neutralizing antibody responses and cellular responses against SARS-CoV-2 Omicron subvariants after mRNA SARS-CoV-2 vaccination in kidney transplant recipients.

Although the mRNA SARS-CoV-2 vaccine has improved the mortality rate in the general population, its efficacy against rapidly mutating virus strains, especially in kidney transplant recipients, remains unclear. We examined the anti-SARS-CoV-2 spike protein IgG antibody and neutralizing antibody titers and cellular immunity against B.1.1, BA.1, and BA.5 antigens in 73 uninfected kidney recipients and 16 uninfected healthy controls who received three doses of an mRNA SARS-CoV-2 vaccine. The IgG antibody titers were significantly lower in recipients than in healthy controls. Similarly, neutralizing antibody titers against three viral variants were significantly lower in recipients. When the virus was mutated, the neutralizing antibody titers decreased significantly in both groups. In cellular immunity analysis, the number of spike-specific CD8 + non-naïve T cells against three variants significantly decreased in recipients. Conversely, the frequency of spike-specific Th2 CD4 + T-cells in recipients was higher than that in healthy controls. Nineteen recipients and six healthy controls also received a bivalent omicron-containing booster vaccine, leading to increase IgG and neutralizing antibody titers in both groups. After that, eleven recipients and five healthy controls received XBB.1.5 monovalent vaccines, increasing the neutralizing antibody titers against not only XBB.1.5, but also EG.5.1 and BA.2.86 antigens in kidney recipients. Although kidney recipients did not gain sufficient immunity against Omicron BA.5 with the third dose of vaccine, humoral response against mutant SARS-CoV-2 lineages significantly increased after bivalent Omicron-containing booster vaccine and the XBB.1.5 monovalent vaccine. Therefore, it is important for kidney recipients to continue to administer updated vaccines.

Hepatitis B Birth Dose Vaccination Improvement Initiative: The 24-Hour Baby Bundle.

BACKGROUND: An estimated 25,000 infants are born to mothers diagnosed with hepatitis B virus (HBV) each year in the United States. Administration of the birth dose HBV vaccine prevents transmission during delivery. Despite national guidelines promoting vaccination within 24 hours of birth, fewer than 70% of infants receive the dose in their first 3 days of life. To improve compliance with national recommendations, Northwestern Medicine implemented a bundled care initiative in the well newborn nursery, entitled the 24-hour baby bundle (24-HBB). PURPOSE: Evaluate the 24-HBB's effect on improving time to HBV vaccine administration. METHODS: The 24-HBB was created by an interdisciplinary team and implemented on February 17, 2020. Bundled care begins at 23 hours of life, starting with the HBV vaccine, followed by bath, weight, and congenital heart disease screening, and ending with metabolic screening. We conducted a retrospective cohort study of 22,057 infants born at Northwestern Medicine Prentice Women's Hospital in Chicago, Illinois. Our sample included preintervention birthdates between February 16, 2019, and January 16, 2020, and postintervention birthdates between March 17, 2020, and February 16, 2021, with a 2-month washout education period between January 17, 2020, and March 16, 2020. RESULTS: Hepatitis B virus immunization within 24 hours increased significantly from 43.83% to 66.90% (P < .0001). In addition, overall hepatitis B immunization prior to discharge significantly increased after implementation of the 24-HBB (98.18% vs 98.82%, P < .0001). IMPLICATIONS FOR PRACTICE AND RESEARCH: The 24-HBB is effective at increasing rates of HBV immunization within 24 hours of birth. Newborn nurseries may benefit from similar initiatives to prevent hepatitis B infection, satisfy national recommendations, and promote childhood vaccination compliance.

Profiling of Early Immune Responses to Vaccination Using THP-1-Derived Dendritic Cells.

The COVID-19 pandemic has made assessing vaccine efficacy more challenging. Besides neutralizing antibody assays, systems vaccinology studies use omics technology to reveal immune response mechanisms and identify gene signatures in human peripheral blood mononuclear cells (PBMCs). However, due to their low proportion in PBMCs, profiling the immune response signatures of dendritic cells (DCs) is difficult. Here, we develop a predictive model for evaluating early immune responses in dendritic cells. We establish a THP-1-derived dendritic cell (TDDC) model and stimulate their maturation in vitro with an optimal dose of attenuated yellow fever 17D (YF-17D). Transcriptomic analysis reveals that type I interferon (IFN-I)-induced immunity plays a key role in dendritic cells. IFN-I regulatory biomarkers (IRF7, SIGLEC1) and IFN-I-inducible biomarkers (IFI27, IFI44, IFIT1, IFIT3, ISG15, MX1, OAS2, OAS3) are identified and validated in vitro and in vivo. Furthermore, we apply this TDDC approach to various types of vaccines, providing novel insights into their early immune response signatures and their heterogeneity in vaccine recipients. Our findings suggest that a standardizable TDDC model is a promising predictive approach to assessing early immunity in DCs. Further research into vaccine efficacy assessment approaches on various types of immune cells could lead to a systemic regimen for vaccine development in the future.