Vaccine Response Research Articles

COVID-19 Vaccine Response in Pediatric Oncology Patients.

Pediatric oncology and hematopoietic stem cell transplant (HSCT) patients may fail to mount an appropriate immune response to COVID-19 vaccinations. The immunologic response to initial SARS-CoV-2 vaccination was studied in 93 pediatric patients with hematologic malignancy, solid tumors, or post-HSCT. The majority of patients who were not receiving chemotherapy showed a positive humoral and cell-mediated response to COVID-19 vaccination. In contrast, variable responses to vaccination were seen in patients receiving chemotherapy. Patients with a normal lymphocyte count showed higher rates of seroconversion than their lymphocytopenic counterparts. This report details pediatric oncology and HSCT patients' immunologic responses to COVID-19 vaccination during all phases of treatment.

Growth hormone replacement therapy enhances humoral response to COVID-19 mRNA vaccination in patients with adult-onset growth hormone deficiency.

Given the established link between GH/insulin-like growth factor 1 (IGF-1) deficiency and severe COVID-19 outcomes, this research seeks to determine whether GH therapy can enhance vaccine efficacy in patients with adult-onset growth hormone deficiency (aGHD). We conducted an observational retrospective study involving two groups: a cohort of 10 patients (8 females, 2 males) with obesity and aGHD who initiated recombinant GH replacement therapy at a standard dose of 0.1mg/day six months to one year before their first vaccine dose, and a matched control group of 7 patients (5 females, 2 males) with aGHD who had not started GH treatment. Both groups were matched for age, gender, and body mass index (BMI) to ensure comparability. Blood samples were collected 3 to 6months after the third booster dose of the COVID-19 vaccine (BNT162b2, Pfizer-BioNTech) and analyzed for anti-SARS-CoV-2 antibodies using a commercially available assay. The GH-treated group exhibited a significantly greater humoral response compared to the untreated group, with a mean antibody titer of 19,122.1 ± 7,736.84 U/mL versus 9,539.14 ± 5,408.90 U/mL in the control group (p = 0.01). Multivariate regression analysis revealed that GH replacement therapy was the only statistically significant predictor of vaccine response, while factors such as male sex, age, and visceral adipose tissue showed negative correlations that did not reach significance. Our findings suggest that GH replacement therapy may enhance the immune response to COVID-19 vaccination in patients with aGHD, potentially improving their overall metabolic health and immune function.

Effect of vaccination against foot-and-mouth disease during mid-pregnancy on the neutralizing antibody response in the cow.

As pregnancy can adversely affect the immune response of vaccination against foot and mouth disease virus (FMDV) due to physiological immunosuppressive milieu, we tested the effect of FMDV vaccination during mid-gestation on the antibody response. Pregnant and non-pregnant cows of crossbred and indigenous breed (n=28/group) were vaccinated with inactivated FMD vaccine covering O, A, and Asia1 serotypes and the sera were harvested at weekly interval till day 42 post-vaccination. Virus neutralization test (VNT) was done and the analysis of log10 VN50 antibody titer by mixed model ANOVA indicated that pregnancy did not significantly affect the log10 VN50 titer for FMDV serotype O and Asia1. Though pregnancy significantly decreased the titer for FMDV serotype A, the effect size was small. The experiment was repeated in purebred HF cows (n=10/group) and the results were reproducible. It was concluded that mid-pregnancy would not hamper the herd immunity to FMD vaccination in the cow.

Efficacy, immunogenicity, and safety of the Novavax COVID-19 vaccine in immunocompromised patients: A targeted literature review.

Individuals who are immunocompromised (IIC) may have impaired infection prevention/resolution, potentially causing increased disease severity, complications, and healthcare-system strain. Exclusion of IIC from COVID-19 vaccine trials and limited real-world Novavax COVID-19 vaccine assessments have resulted in a data gap. This article provides a review of literature on IIC who received the Novavax COVID-19 vaccine. A targeted literature search of BIOSIS Previews®, Embase®, Embase Preprints, MEDLINE®, and publicly available content was performed to identify published clinical data assessing efficacy, immunogenicity, and safety of the Novavax COVID-19 vaccine in IIC, with predefined terms for immune-modifying diseases/conditions and medications. Identified publications were screened to ensure they described study data from IIC who received the Novavax COVID-19 vaccine. The search (through October 2024) identified 137 reports indicating use of the Novavax COVID-19 vaccine in IIC. Screening resulted in 10 publications for review; exclusionary reasons included a lack of vaccine-specific data (i.e., limited [<0.2% or n<3] vaccine recipients, pooled/aggregated cohorts) and/or IIC population. Conditions described include HIV, multiple sclerosis, inflammatory rheumatic diseases, transplant recipients, and hematologic malignancies. Overall, the Novavax COVID-19 vaccine was immunogenic and had a tolerable safety profile across diverse populations of IIC; some outcomes varied based on condition, disease, and/or concomitant medication(s). Limited efficacy data indicates that the Novavax COVID-19 vaccine may help protect IIC against symptomatic/severe COVID-19; however, additional studies with larger sample sizes are needed. Future research should include disease-specific populations to assess how individual characteristics (e.g., disease state, concomitant medications, prior COVID-19 vaccination) impact vaccine response.

A-910823, a squalene-based emulsion adjuvant, enhances robust and broad immune responses of quadrivalent influenza vaccine in ferrets.

Robust and broad protective immunity is typically elicited by co-administration of an adjuvant with vaccine antigens. A-910823, a squalene-based emulsion adjuvant, has been approved in Japan. It effectively enhances the humoral and cellular immunity of S-268019-b, a recombinant COVID-19 vaccine; however, the adjuvant effects of A-910823 on other vaccines, including influenza vaccine, have not been evaluated. Here, a ferret model was employed to investigate the adjuvant effects of A-910823 when combined with split-inactivated quadrivalent influenza vaccine (QIV). We demonstrate that combination of A-910823 with QIV enhances the neutralizing antibody titer and its breadth against non-vaccine strains. Also, the protective efficacy of A-910823-adjuvanted QIV against virus challenge has been confirmed. Of note, QIV combined with A-910823 caused only minor detectable side effects, whereas a significant increase in fever was observed after two doses of mRNA-LNP in ferrets. This study provides information on the effectiveness and safety of A-910823-adjuvanted QIV and suggests the usefulness of the ferret model for evaluating vaccine-induced reactogenicity.

P-616. Sociodemographic and Clinical Factors Affecting Vaccination after Pediatric Solid Organ Transplantation at Duke University

Abstract Background Pediatric solid organ transplant (SOT) recipients are at increased risk for vaccine preventable illnesses (VPI). They frequently receive vaccines after transplantation when immunosuppressive medications and cytopenias may impact their immune response to routine childhood vaccines. Current guidelines recommend monitoring vaccine-specific serologies to ensure optimal vaccine responses and to guide the need for repeat doses. Methods In this single-center retrospective cohort study, a multivariate logistic regression model was used to determine the sociodemographic and clinical factors associated with delays in starting post-transplant vaccines and adherence to post-vaccine serologic monitoring among 199 pediatric patients who received a SOT at Duke University between 2014-2023. The prevalence of cytopenias at the time of post-transplant vaccination was also described. Results Out of 150 children eligible for post-transplant vaccines (Table1), 48 (32%) failed to start catch-up vaccines within 2 years of transplantation. Older children (OR=0.877, 0.83-0.927) and children with private insurance (OR=0.458, 0.211-0.993) had significantly decreased odds of early catch-up vaccines (Table 2). Hepatitis B serologies were obtained in 23% of patients after post-transplant vaccination, but titers against the remaining non-live childhood vaccines were only obtained in 1-8% of children (Table 3). Approximately 53% of all children had neutropenia or lymphopenia (less than 1500 x 10^6 cells/L) at the time of post-transplant vaccination, with heart and intestinal/multi-visceral transplant recipients having the highest rates at ∼75% (Table 4). Conclusion These findings identify pediatric SOT recipients most at risk for delayed post-transplant vaccines. The associations between vaccine delay and private insurance and older age warrant further investigation. The extremely low rates of vaccine-specific serologic monitoring and the high prevalence of cytopenias at the time of vaccination raise concerns that pediatric SOT recipients are insufficiently protected from VPI. Future work will determine the impact of cytopenias on vaccine response and will address inequities in vaccination among pediatric SOT recipients. Disclosures All Authors: No reported disclosures

P-7. A study of influenza vaccination response in disabled stroke patients

Abstract Background To date, no clinical study has confirmed the clinical efficacy of routine annual vaccination in stroke patients. The primary objective was to study the immunologic response to influenza vaccination between functional-dependence (FD) and functional-independence (FI) ischemic stroke patients. Median hemagglutination titers at T0 and T1 Methods A prospective observational study was conducted between 2023 and 2024 at Ramathibodi Hospital. Old ischemic stroke patients were screened for eligibility. Enrolled patients received standard doses of inactivated trivalent influenza vaccine. Data on patient demographics were retrieved. Blood samples were collected for hemagglutination inhibition (HAI) before and 4-8 weeks after vaccination to determine seroprotection and seroconversion rates. Results As per the interim analysis, 198 patients were enrolled, and 161 individuals have completed the HAI analysis. The mean ages (±SD) of the control (C), FI, and FD groups were 69.4±7.4 years, 71.4±8.6, and 75.9±8.3, respectively (p&amp;lt; 0.001). The FD group had significantly higher baseline IFN-α2, IFN-γ, IL-6, IL-12p, and IL-18 levels than the FI and C groups. Before (T0) and after (T1) vaccination, the proportion of participants with HAI titers &amp;gt;1:40 on the A/Sydney (H1N1) strain in the FI group was significantly higher than in the FD group (p=0.031 and 0.003 at T0 and T1, respectively) similarly to the A/Darwin (H3/N2) and the B/Austria strains and individuals achieved titer &amp;gt;1:160 (p=0.046 at T1). The C group displayed the highest seroconversion rates compared to the FI and the FD groups at 34.2%, 25.4%, and 19.4% (p=0.033). There were three probable and 23 possible influenza infections three months after enrollment. Twenty-two of 198 patients developed mild adverse events associated with influenza vaccination. Conclusion The FI group achieved higher seroprotection and seroconversion rates than the FD group. The possible associated factors were higher levels of pro-inflammatory cytokines at baseline, resulting in better vaccination responses in the FI group. Therefore, the FD group may require a different influenza vaccination strategy to achieve more appropriate immune responses. Disclosures All Authors: No reported disclosures

P-607. Immunogenicity and Tolerability of the Novavax Nanoparticle Influenza Vaccine (NIV) and COVID-Influenza Combination Vaccine (CIC)

Abstract Background There is a public health need for annual immunizations against both SARS-CoV-2 and influenza viruses. We developed both a standalone saponin-adjuvanted (Matrix-M™) recombinant quadrivalent hemagglutinin (HA) nanoparticle influenza vaccine (qNIV), and a COVID and influenza combination (CIC) vaccine, comprising recombinant SARS-CoV-2 Spike (rS) (NVX-CoV2373), qNIV, and Matrix-M adjuvant.Table 1.Study design Methods Participants in Australia and New Zealand (1571 treated, including 864 in the CIC group) aged 50–80 years were randomized equally to receive one intramuscular dose of vaccine in 1 of 20 groups: either 1 of 11 different dose/formulations of CIC, 1 of 3 formulations of qNIV with Matrix-M, 1 of 4 formulations of standalone rS with Matrix-M, or 1 of 2 influenza vaccine comparators (Fluzone HD® or FLUAD®) (Table 1). Immunogenicity assessments included anti-spike IgG, SARS-CoV-2 neutralizing antibody (vaccine-homologous and -heterologous strains), wild-type influenza HAI antibodies (vaccine-homologous strains). Reactogenicity was assessed for 7 days following vaccination and SAEs, AESIS, and MAAEs were assessed throughout the study.Table 2.CIC and qNIV post-vaccination immunogenicity assessments (Day 21, per-protocol analysis set) Results qNIV ([HA60/M75], n=75) HAI and neutralizing antibody responses were significantly higher than FLUAD and Fluzone HD against both vaccine-homologous A strains, particularly against H3N2 (Table 2). CIC ([HA60/rS35/M75], n=75) showed evidence of rS and HA antigen interference, but achieved anti-spike IgG and influenza HAI antibody responses that were comparable to both the standalone rS vaccine (NVX-CoV2373) and FLUAD /Fluzone HD, respectively (Table 2). All qNIV and CIC formulations evoked local and systemic solicited adverse events at rates and severities less than or comparable to FLUAD and Fluzone HD (Figure 1). There was no dose dependence of HA, rS antigens, or Matrix-M on tolerability. SAEs were infrequent in all groups.Figure 1.Solicited (A) local and (B) systemic TEAEs within 7 days of vaccination (safety analysis population) Conclusion qNIV produced improved wild-type HAI antibody responses as compared to FLUAD and Fluzone HD against influenza A strains, notably against H3N2. CIC achieved both anti-spike IgG responses comparable to the authorized prototype NVX-CoV2373 rS vaccine and HAI responses comparable to licensed enhanced influenza comparators. CIC and qNIV had safety profiles comparable to Fluzone HD and FLUAD. Disclosures Vivek Shinde, MD, MPH, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Joyce S. Plested, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Tim Vincent, n/a, Novavax, Inc.: Employee|Novavax, Inc.: Stocks/Bonds (Public Company) Mingzhu Zhu, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Shane Cloney-Clark, n/a, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Zhaohui Cai, PhD, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Bridget Riviers, Ph.D., Novavax, Inc.: Employee|Novavax, Inc.: Stocks/Bonds (Public Company) Farnaz Mahkhou, Ph.D., Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Anthony M. Marchese, PhD, Novavax Inc: Employee|Novavax Inc: Stocks/Bonds (Public Company) Iksung Cho, MS, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company) Louis F. Fries, III, MD, Novavax, Inc.: contractor for Novavax|Novavax, Inc.: Stocks/Bonds (Public Company) Wayne Woo, MS, Novavax, Inc.: employee|Novavax, Inc.: Stocks/Bonds (Public Company)

P-1969. Safety, Immunogenicity, and Pharmacokinetics of Repeat Dosing with AZD7442 (Tixagevimab/Cilgavimab): Final Analysis of the ENDURE Phase 2, Dose-Ranging Study in Immunocompromised Participants

Abstract Background Prior studies of the SARS-CoV-2 monoclonal antibody (mAb) combination AZD7442 (tixagevimab/cilgavimab) included limited numbers of immunocompromised (IC) participants, the target population for COVID-19 pre-exposure prophylaxis. We report repeat dosing data of AZD7442 in an IC population. Methods The randomized, open-label, ENDURE study (NCT05375760) enrolled individuals aged ≥ 18 yrs, weighing ≥ 40 kg, moderately to severely IC or at risk of inadequate vaccine response, and SARS-CoV-2–negative at baseline. Participants were randomized 1:1 to AZD7442 600 mg intramuscularly (IM) on Day 1 + 300 mg IM every 3 months (Arm A) or AZD7442 1200 mg intravenously on Day 1 + 600 mg IM every 6 months (Arm B). Month-12 dose was not administered due to non-safety related trial termination. Primary objectives were safety and immunogenicity (anti-drug antibodies; ADAs); secondary objectives were pharmacokinetics (PK) and SARS-CoV-2–neutralizing antibody (nAb) titers. Results Of 251 randomized participants, 124 were dosed in Arms A and B. Median exposure duration was 373.5 days in both arms. Participants’ mean age was 55.7 yrs, 53.2% were female, and 81.9% had not received a COVID-19 vaccine prior to study start. Adverse events (AEs) occurred in 84 (67.7%) participants in Arm A and 66 (53.2%) in Arm B. The proportion of participants with serious AEs (overall 9.3%) and AEs of special interest (3.1%) was similar across doses and following repeated dosing (Table 1). ADA incidence (% treatment-emergent ADA+) was similar in both arms (Arm A, 0.9%; Arm B, 2.7%) with no apparent impact of ADAs on safety, PK, or SARS-Cov-2 nAb titers (Table 2). Following dosing, mAb serum concentrations were stable in Arms A and B, with no accumulation observed (Figure 1). A strong correlation (R &amp;gt; 0.78) was observed between pseudovirus nAb titers and AZD7442 serum concentrations for both arms (Figure 2). Conclusion AZD7442 safety and ADA profiles were consistent across doses and dosing regimens. No accumulation in serum AZD7442 concentrations was observed with repeat dosing compared with the initial dose for each arm. These data may help inform development of future long-acting SARS-CoV-2 mAbs. Disclosures Taylor Cohen, PhD, AstraZeneca: Employee, holds or may hold stock Chigo Munthali, MBBS, MSc, DPM, MFPM, CCT(Pharma Med.), AstraZeneca: Employee, holds or may hold stock Herve Tchouakam Kouekam, MSc, Cytel Inc. (contracted to AstraZeneca): Employee of Cytel Inc. Sam Matthews, MSc, Exploristics Ltd. (contracted to AstraZeneca): Employee of Exploristics Ltd. Audrey Sharbaugh, PhD, AstraZeneca: Employee, holds or may hold stock Rohini Beavon, PhD, AstraZeneca: Employee, holds or may hold stock Dilki Wickramarachchi, PhD, AstraZeneca: Employee, holds or may hold stock Sharon Otal, HBSc, MBA, AstraZeneca: Employee, holds or may hold stock Haitao Yang, PhD, AstraZeneca: Employee, holds or may hold stock Anastasia A. Aksyuk, PhD, AstraZeneca: Employee, holds or may hold stock Lindsay E. Clegg, PhD, AstraZeneca: Employee, holds or may hold stock Huixia Zhang, PhD, AstraZeneca: Employee, holds or may hold stock Antonella Nadia Tuillio, MD, AstraZeneca: Employee, holds or may hold stock Seth Seegobin, PhD, AstraZeneca: Employee, holds or may hold stock Katie Streicher, PhD, AstraZeneca: Employee of AstraZeneca and may own AstraZeneca stock or stock options. David Wheeler, MD, AstraZeneca: Funding for clinical research|Gilead: Funding for clinical research|Janssen: Funding for clinical research Lee-Jah Chang, MD, AstraZeneca: Employee of AstraZeneca Hugh Montgomery, MD, AstraZeneca: Advisor/Consultant|Millfield Medical Ltd.: Advisor/Consultant|Millfield Medical Ltd.: Consulted for Millfield Medical Ltd during the development of a new Closed Circuit Continuous Positive Airway Pressure machine.|UK NIHR BRC at University College London Hospitals: Funding

P-597. Amezosvatein Demonstrates Non-Inferior Immunogenicity and Superior Tolerability Head-to-Head vs Shingrix in a Phase 2 Herpes Zoster Vaccine Trial

Abstract Background Low uptake and significant second-dose avoidance for herpes zoster (HZ) vaccination are behaviors linked to poor tolerability of the existing AS01B-adjuvanted recombinant gE herpes zoster vaccine, Shingrix, and represent an unmet medical need for a less reactogenic herpes zoster vaccine. Amezosvatein (CRV-101) is an investigational recombinant gE vaccine using a third-generation synthetic adjuvant (SLA-SE) targeting the human TLR4 receptor with improved tolerability and non-inferior immunogenicity. Humoral Immunogenicity: Anti-gE Antibody VRR and GMFR, and Anti-VZV Neutralizing Antibody GMFR Vaccine Response Rate, defined as a 4-fold rise in antibody concentration from baseline, Geometric Mean Fold-Rise (GMFR) in anti-gE ELISA from baseline, and fold rises in neutralizing antibody were identical or higher for amezosvatein Methods A randomized, observer-blind, active-controlled, multi-center Phase 2 trial of amezosvatein versus Shingrix enrolled 876 participants aged 50+. Participants received two injections of either Shingrix or amezosvatein at up to 100 μg of gE antigen with 5, 10, or 15 μg of SLA-SE. The primary endpoints of the study compared safety/tolerability and non-inferiority of immunogenicity of amezosvatein vs Shingrix. Amezosvatein demonstrates superior tolerability to Shingrix Amezosvatein demonstrated a clinically superior tolerability profile compared to Shingrix as measured by Grade 2/3 solicited local and systemic adverse events. Results Amezosvatein at 100 μg gE/15 μg SLA-SE demonstrated immunogenicity non-inferior to Shingrix at Day 84 as measured by anti-gE ELISA Geometric Mean Concentration (50,000 mIU/mL vs. 56,959 mIU/mL, adjusted ratio 0.89, 80% CI 0.79; 1.01). Vaccine Response Rate, defined as a 4-fold rise in antibody concentration from baseline, Geometric Mean Fold-Rise (GMFR) in anti-gE ELISA from baseline, and fold rises in neutralizing antibody were identical or higher for amezosvatein (Figure 1). Amezosvatein demonstrated a clinically superior tolerability profile compared to Shingrix as measured by Grade 2/3 solicited local and systemic adverse events. Grade 2/3 solicited AEs were reported by 7.3% of amezosvatein recipients versus 33.3% of Shingrix recipients. This difference was statistically significant in a post hoc analysis (p&amp;lt; 0.001) (Figure 2). Conclusion Our findings suggest amezosvatein has been shown as efficacious with a potentially better tolerability profile, making it a potentially-attractive alternative for the prevention of herpes zoster. Global Phase 3 trials of amezosvatein are anticipated to begin shortly. Disclosures Lisa R. Shelton, ARNP, Curevo Vaccine: Salary|Curevo Vaccine: Stocks/Bonds (Private Company) Soren Gantt, MD PHD MPH FRCPC, Altona Diagnostics: Grant/Research Support|Curevo Vaccine: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Meridian Biosciences: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|VBI: Grant/Research Support Guy De La Rosa, MD, Curevo Vaccine: Employee|Curevo Vaccine: Stocks/Bonds (Private Company) David A. G. Skibinski, PhD, Curevo Vaccine: Salary|Curevo Vaccine: Stocks/Bonds (Private Company) George Simeon, MPH, Curevo Inc.: Board Member|Curevo Inc.: salary|Curevo Inc.: Stocks/Bonds (Private Company) David Miller, BA, Curevo Vaccine: Employee|Curevo Vaccine: Stocks/Bonds (Private Company)

P-1852. Investigating the infant gut microbiome in relation to R21/Matrix-M™ vaccine immunogenicity and efficacy

Abstract Background R21/Matrix-M™ malaria vaccine was recently licensed in young children following good vaccine efficacy and induction of high titre antibody responses to the central repeat (NANP) of the P. falciparum circumsporozoite protein. Variability in NANP responses and efficacy was noted in the populations assessed and according to age. Links between the gut microbiome and the immune system mean early life gut microbiome is an important consideration when understanding vaccine responses. We investigated the relationship of these and participant factors with the gut microbiome in Burkinabe infants in the R21/Matrix-M™ phase IIb trial. Methods A phase IIb double-blind, randomised controlled trial assessing safety, immunogenicity and efficacy of R21/Matrix-M™ in 5-17 month olds took place in Nanoro, Burkina Faso from 2019 to 2023. Rectal swabs were collected at baseline and a year later, for both malaria vaccine (n=223) and control participants (n=77). Participant factors (i.e. age, gender, feeding, number of siblings, and Z-score), malaria episodes, and anti-NANP antibody responses were measured. Microbiome was assessed using 16S rRNA gene sequencing. Microbiome alpha- and beta- diversity were characterized, and microbial abundances were analysed using univariate and multivariate models. Results Participant microbiomes showed two discernible compositional phenotypes at baseline and follow-up timepoints. The microbiome of majority of participants (93%) were predominantly Firmicutes (39%) and Bacteroidetes (37%) and low in Proteobacteria (13%). However, a subset of participants (7%) had microbiomes that were mainly Proteobacteria (63%). Within-individual alpha-diversity significantly varied with age, but not other participant factors. Relative abundances of certain bacteria were associated with age. Microbial abundances will be analysed and presented against antibody responses, as well as the number of clinical malaria episodes in the first two years. Conclusion We describe the microbiome of Burkinabe infants within the context of R21/Matrix-M™ malaria vaccination. This dataset provides insight into a previously underrepresented population during early life, which is a key window for immunological and microbiome development. Disclosures Adrian V S Hill, PhD, Serum Institute of India: Grant/Research Support|Serum Institute of India: I am named as a co-inventor on patent applications related to R21

P-1987. Effectiveness of Tixagevimab-Cilgavimab as Pre-Exposure Prophylaxis in Patients Undergoing Hematopoietic Cell Transplant or Chimeric Antigen Receptor T-cell Therapy

Abstract Background Tixagevimab-cilgavimab (tixa-cil), was approved for emergency use authorization by the FDA in December of 2021 for pre-exposure prophylaxis of the COVID-19 virus in immunocompromised populations due to concerns about vaccine efficacy. Data regarding real world efficacy of tixa-cil in preventing SARS-CoV-2 infection in immunocompromised patients is limited.Table 1Patient Demographics Methods We conducted a retrospective analysis of all patients who had received hematopoietic cell transplantation (HCT) or chimeric antigen receptor T-cell (CAR-T cell) therapy between 12/1/2021-12/1/2022 at the University of North Carolina Bone Marrow Transplant and Cellular Therapy Program and were eligible to receive tixa-cil as pre-exposure prophylaxis. Patient demographics, underlying malignancy type, COVID-19 vaccine status, data and number of tixa-cil injections, cellular infusion type, presence of GVHD, adverse events, and cause of death if related to COVID-19 were all collected.Table 2Therapeutic Agents Used For Treatment of COVID-19 Results Of 184 eligible patients, 113 (61%) received at least one tixa-cil injection. Forty-five cases of either documented or reported COVID-19 infection following cell infusion (including 8 recurrent infections) were identified. Of the 113 patients who received tixa-cil, 14 (12%) had a documented positive COVID test within 6 months. In comparison, 23 (32%) of the 71 patients who did not receive tixa-cel had a documented positive COVID test, (p=0.0013, Fisher’s exact test), OR=0.2951. Of 13 COVID-related hospitalizations, only one occurred in a patient who received tixa-cil, (p=0.0048, Fisher’s exact), OR=0.0641. Number of Patients with Documented COVID Infections Who Did and Did Not Receive Tixa-Cil Conclusion Our findings indicate that tixa-cil was effective as pre-exposure prophylaxis in reducing SARS-CoV-2 infection and disease severity in a highly immunocompromised patient population. While the FDA removed authorization for ongoing use of tixa-cil in January 2023 due to its ineffectiveness against the Omicron variants, our data suggest that mAbs are highly effective in providing protective passive immunity to patients at risk of impaired vaccination responses. Pemibivart, a new anti-SARS-CoV-2 spike protein mAb, was recently authorized by the FDA. Our results suggest a clinical benefit for this therapy; however, real world studies will be needed to determine actual efficacy. Number of Patients Hospitalized Related to COVID Infection Who Did and Did Not Receive Tixa-Cil Disclosures Jonathan Ptachcinski, PharmD, Johnson &amp; Johnson: Company Employee

P-44. Immunogenicity and Safety of High-dose versus Standard-dose Quadrivalent Inactivated Influenza Vaccine in Patients Living with HIV: A Randomized Controlled Trial

Abstract Background Influenza can lead to severe complications in patients living with HIV (PLWH). Annual standard-dose (SD) quadrivalent inactivated influenza vaccine (QIIV) is recommended for PLWH, although it is associated with poor vaccine response. We aimed to investigate the immunogenicity and safety of high-dose (HD) versus SD QIIV in PLWH, as well as safety. Methods We conducted a randomized, open-label, controlled trial to compare the immunogenicity of the 2023 southern hemisphere HD QIIV at 60 μg (Efluelda, Sanofi) versus SD QIIV at 15 μg (Fluarix tetra, Sanofi) in patients living with HIV (PLWH) during August and November 2023. Seroprotection (SP), defined as serum hemagglutination-inhibition antibody titers ≥1:40 at 1 month post-vaccination, was assessed. Adverse events (AEs) following vaccination were also evaluated. Results We enrolled 110 patients who received the study vaccine, and 103 (52 HD; 51 SD) were eligible for analysis. Among them, 65 (62.1%) were male, with a mean age (SD) of 49.6 (11.2) years and a median CD4 count (IQR) of 555 (418-680) cells/mm3. The integrase strand transfer-based regimen was the most common antiretroviral regimen (57.3%), and the majority had an undetectable HIV viral load (93.2%). Fifty-two (50.5%) achieved SP to all strains (A/H1N1, A/H3N2, B/Victoria and B/Yamagata) after vaccination. Those who received HD QIIV reached SP significantly more compared to SD QIIV (61.5% vs. 39.2%, p = 0.02). In particular, SP to the A/H3N2 strain was significantly greater in the HD QIIV group compared to the SD QIIV group (76.9% vs. 52.9%, p = 0.011). Use of HD QIIV were independent factors for SP to all strains (OR 2.7, 95%CI 1.9-6.1, p = 0.02) and SP to the A/H3N2 strain (OR 3.2, 95%CI 1.4-7.8, p = 0.01). Twenty-nine (57.3%) participants in the HD group reported AEs, including muscle ache (36.5%), pain at the injection site (21.2%), and fever (13.5%). Those were all non-severe and comparable to those receiving SD QIIV. Conclusion HD QIIV could offer significantly better immunogenicity across all strains, especially the A(H3N2) strain, compared to SD QIIV in PLWH and should be considered as the preferred influenza vaccine for this population, without safety concerns. TCTR20230501002. Disclosures All Authors: No reported disclosures

A Pentavalent HIV-1 Subtype C Vaccine Containing Computationally Selected gp120 Strains Improves the Breadth of V1V2 Region Responses

Background: HIV-1 envelope (Env) variable loops 1 and 2 (V1V2) directed non-neutralizing antibodies were a correlate of decreased transmission risk in the RV144 vaccine trial. Thus, the elicitation and breadth of antibody responses against the V1V2 of HIV-1 Env are important considerations for HIV-1 vaccine candidates. The V1V2 region’s highly variable nature and the extensive diversity of subtype C HIV-1 Envelopes (Envs) make the V1V2 response breadth a high priority for HIV-1 vaccine regimens aiming for V1V2-mediated protection in Southern Africa. Here, we determined whether the breadth of the anti-V1V2 vaccine response can be broadened by including HIV-1 Env strains computationally designed to enhance the coverage of subtype C V1V2 sequence diversity. Methods: Three subtype C Env strains were selected to maximize antibody binding coverage while complementing subtype C vaccine gp120s that were given in human clinical trials in South Africa, as well as to improve epitope accessibility. Humoral immunogenicity of a novel trivalent gp120 vaccine immunogen, a bivalent gp120 boost already in clinical trials (1086C and TV1), and a pentavalent (all five gp120s combined) were evaluated in a preclinical immunization study in guinea pigs. The pentavalent combination was further evaluated with alum versus glucopyranosyl lipid adjuvants formulated in squalene-in-water emulsion (GLA-SE) adjuvants in non-human primates. The breadth of the anti-V1V2 response was assessed using an array of cross-subtype variable loops 1&amp;2 (V1V2) scaffold proteins and linear V2 peptides. Results: The breadth of the IgG response against V1V2 antigens of the trivalent and pentavalent groups was comparable, and both were greater than the breadth of the bivalent group. Linear epitope mapping showed that two linear epitopes in V2 were targeted by the vaccinated animals: the V2 hotspot focused at 169K that potentially correlated with decreased HIV-1 risk in RV144 and the V2.2 site (179LDV/I181) that is part of the integrin α4β7 binding site. The bivalent vaccine elicited a significantly higher magnitude of binding to the V2 hotspot compared to the trivalent vaccine whereas the trivalent vaccine elicited significantly higher binding to the V2.2 epitope compared to the bivalent vaccine, while the pentavalent recognized both regions. Conclusions: These results demonstrate that the three new computationally selected subtype C Envs successfully complemented 1086C and TV1 for broader V1V2 antibody responses, and, in concert with adjuvants that stimulate V1V2 responses, can be considered as part of a rationale immunogen design to improve V1V2 IgG coverage in future vaccine trials in South Africa.

Recombinant XBB.1.5 boosters induce robust neutralization against KP.2- and KP.3-included JN.1 sublineages

The newly emerged variants of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) demonstrate resistance to present therapeutic antibodies as well as the capability to evade vaccination-elicited antibodies. JN.1 sublineages were demonstrated as one of the most immune-evasive variants, showing higher neutralization resistance compared to XBB.1.5. In this study, serum samples were collected from adult participants including those who had gone through the BA.5/BF.7, EG.5/HK.3 and XBB/JN.1 infection waves, characterized by different infection and vaccination histories. We evaluated the neutralization in these serum samples against pseudoviruses of Omicron lineages. We further investigated humoral immune response of recombinant XBB vaccines against Omicron variants and estimated the neutralization resistance of JN.1 sublineages, including KP.2 and KP.3. Our results showed that sera from previous circulating Omicron subvariant breakthrough infections exhibited low neutralization against pseudoviruses of Omicron lineages. The GMTs of 50% neutralization against all tested pseudoviruses were significantly elevated in sera from individuals who received WSK-V102C or WSK-V102D boosters. Importantly, the GMTs of 50% neutralization in serum samples from individuals 4 months after a WSK-V102D booster against XBB.1.5, JN.1, JN.1.13, KP.2 and KP.3 pseudoviruses were 3479, 1684, 1397, 1247 and 1298, with 9.86-, 9.79-, 8.73-, 8.66- and 8.16-fold increase compared to those without booster, respectively, indicating that boosting with XBB.1.5 subunit vaccines still induced strong antibody responses against JN.1 sublineages. However, JN.1 sublineages, including KP.2 and KP.3, revealed more than 2-fold decreases in neutralizing antibody titers compared to XBB.1.5, suggesting significantly enhanced neutralization evasion and the necessity of boosters based on JN.1, KP.2 or KP.3.

Timing of post-vaccination tests in infants born to mothers with chronic hepatitis B virus infection.

Immunoprophylaxis is routinely recommended for infants born to mothers with hepatitis B virus (HBV) infection within the first 12-24 hours. Detection of hepatitis B surface antibody (HBsAb) resulting from hepatitis B immunoglobulin administered at birth may be perceived as a real vaccine response. This makes it difficult to detect HBV infection. For this reason, it is recommended that infants born to hepatitis B surface antigen positive mothers and who received immunoprophylaxis at birth should have HBsAb testing when they are 9-15 months old.

Assessment of Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV) as Complementary Biomarkers to Torquetenovirus (TTV)

Recent studies have identified Torquetenovirus (TTV) as a promising biomarker of immune competence, particularly in assessing the vaccine response of solid organ transplant (SOT) recipients. However, given the individual variability of viral load, it is not yet possible to define "normal levels”. Nevertheless, TTV is just one component of the broader Anelloviridae family, which also includes Torquetenominivirus (TTMV) and Torquetenomidivirus (TTMDV). This study explores whether the viremia of TTMV and TTMDV offers a stronger predictive marker for vaccine efficacy in SOT recipients. A cohort of 168 SOT patients (142 kidney and 26 lung transplant recipients) who received the BNT162B2 mRNA vaccine was examined, with viral loads quantified through virus-specific real-time PCR. While TTV remains a potentially useful biomarker for evaluating immune response, the combined analysis of all anelloviruses viremia provides deeper insights, particularly in cases where TTV is undetectable. Notably, only TTMV exhibited a pattern similar to TTV, suggesting its potential as an alternative biomarker when TTV is absent from the patient’s virome.

Integrative deep immune profiling of the elderly reveals systems-level signatures of aging, sex, smoking, and clinical traits.

Aging increases disease susceptibility and reduces vaccine responsiveness, highlighting the need to better understand the aging immune system and its clinical associations. Studying the human immune system, however, remains challenging due to its complexity and significant inter-individual variability. We conducted an immune profiling study of 550 elderly participants (≥60 years) and 100 young controls (20-40 years) from the RESIST Senior Individuals (SI) cohort. Extensive demographic, clinical, and laboratory data were collected. Multi-color spectral flow cytometry and 48-plex plasma cytokine assays were used for deep immune phenotyping. Data were analyzed using unsupervised clustering and multi-dataset integration approaches. We studied 97 innate and adaptive immune cell populations, revealing intricate age- and sex-related changes in the elderly immune system. Our large sample size allowed detection of even subtle changes in cytokines and immune cell clusters. Integrative analysis combining clinical, laboratory, and immunological data revealed systems-level aging signatures, including shifts in specific immune cell subpopulations and cytokine concentrations (e.g., HGF and CCL27). Additionally, we identified unique immune signatures associated with smoking, obesity, and diseases such as osteoporosis, heart failure, and gout. This study provides one of the most comprehensive immune profiles of elderly individuals, uncovering high-resolution immune changes associated with aging. Our findings highlight clinically relevant immune signatures that enhance our understanding of aging-related diseases and could guide future research into new treatments, offering translational insights into human health and aging. Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy-EXC 2155-project number 390874280.

Integrative Mapping of Pre-existing Immune Landscapes for Vaccine Response Prediction.

Using one of the most comprehensive LAIV datasets compiled to date, immunaut , an integrative machine learning framework, identifies distinct immunophenotypic responder groups shaped by baseline immune landscapes, advancing precision vaccinology and guiding more effective, personalized immunization strategies. Immunaut , an automated framework for mapping and predicting vaccine response immunotypes. Step 1 outlines the identification of vaccine response outcomes using pre- and post-vaccination data integration across immune features, including antibodies, flu-specific T-cells, and immunophenotyping at mucosal and systemic sites. Clustering methods define the vaccine response landscape, stability, and validation through t-SNE-based visualization. Step 2 leverages an automated machine learning modeling approach, to enhance the accuracy and interpretability of vaccine response predictions, enabling stratification and targeted intervention strategies for personalized vaccine immunogenicity.

Long-term antibody trajectories after PPSV23 in elderly: Results from a 4-year follow-up study.

The 23-valent pneumococcal polysaccharide vaccine (PPSV23) is recommended for standalone or sequential use in the elderly in many countries to prevent pneumococcal disease, making it crucial to assess vaccine response and long-term persistence. We aimed to describe the trajectories of circulating antibody levels to the PPSV23 in the elderly following immunization. Eligible individuals aged 65 to 70years were enrolled and vaccinated with one dose of PPSV23. Blood samples were collected at baseline (day 0), 4-6weeks, one year, two years, three years, and four years after vaccination from November 2019 to December 2023. Serotype-specific IgG antibodies were measured for 7(4,6B,9V,14,18C,19F and 23F) out of the 23 vaccine serotypes. Group-based trajectory modeling (GBTM) was applied to identify distinct trajectories of IgG concentration at each visit after immunization. A total of 237 participants completed all six visits over the four-year follow-up period, and the geometric mean concentrations (GMC) of antibodies against the seven serotypes remained elevated above the baseline levels by the fourth year. Females and those with a body mass index (BMI) over 25 have generally higher antibody levels pre- and post-immunization across the seven serotypes, with serotypes 6B, 18C show significant difference in higher BMI individuals, and serotype 9V show significant difference in females after immunization. Based on GBTM, we identified two or three distinct trajectory types of IgG concentration changes across serotypes, with the exception of serotype 4, and we found that participants who showed a more rapid decline in antibody levels two years after vaccination had significantly higher baseline antibody levels. Pneumococcal IgG antibody levels persist for a minimum of four years post-vaccination; Our findings indicate that BMI, gender, and pre-vaccination antibody concentrations should be considered when developing vaccination and revaccination strategies in the elderly.