Background
The Platform Trial In COVID-19 Vaccine priming and BOOsting (PICOBOO) is an MRFF-funded, multi-site, Bayesian adaptive platform trial evaluating COVID-19 booster strategies across 3 sites in Australia. Its flexible design allows for agile responses to the evolving vaccine landscape while improving efficiency and delivering impactful results. Since starting in March 2022, the trial has studied 9 different vaccine boosters and enrolled 1112 participants, with 22 ethics submissions, conducting over study 4800 visits and processing over 70,000 samples. This presentation will reflect on PICOBOO's implementation, identifying key operational challenges, infrastructure limitations, successful adaptations, and areas for improvement.

Key Operational Challenges
• Adapting to a Changing Vaccine Landscape: Frequent protocol amendments increased workload and delays; regulatory, ethics, and contract complexities arose; and limited time and funds hindered bespoke electronic data capture (EDC) development during an emerging pandemic.

• Multi-Layered Approvals: Distinct ethics and multi-jurisdictional governance bodies across various platforms led to inconsistent timelines and implementation delays.

• Fragmented Data & Documentation Systems: Lack of integration between Research EDC (REDCap) and tracking logs increased manual reconciliation efforts and compliance risks.

• Disparate Institutional & Site-Level Infrastructure: Varying governance/documentation methods caused oversight issues and duplication of effort.

Recommendations
• Standardise ethics/governance platforms to streamline approvals.
• Secure funding for a harmonised clinical trial management system (CTMS) to enhance coordination, compliance, and data integrity.
• Implement integrated electronic trial master files within a broader CTMS framework to improve trial documentation.
• Evaluate trade-offs between REDCap, commercial solutions and bespoke EDCs to balance costs with monitoring, database modification and reporting efficiency.

Conclusion
The PICOBOO study highlights the operational complexities of adaptive platform trials in Australia’s current clinical research landscape. Future trials should prioritise coordinated infrastructure improvements to enhance efficiency and scalability to deliver responsive public health impacts and prepare for potential future pandemics.

Objectives
Oral COVID-19 antivirals are important for prevention of severe outcomes from COVID-19, in particular for older people. Molnupiravir and nirmatrelvir/ritonavir, which have different effectiveness and suitability profiles, are currently available in NSW. Our study investigates the characteristics of COVID-19 antiviral dispensing rates over time in people aged 70 and over in NSW.

Methods
This observational population-based study used COVID-19 antiviral dispensing data from the Pharmaceutical Benefits Scheme (PBS) and demographic data from the Medicare Consumer Directory (MCD) for NSW residents aged 70 and over, from 1 March 2022 to 29 September 2024. Dispensing rates were calculated by sex, age group, local health district (LHD) region, and socioeconomic disadvantage using the Index of Relative Socioeconomic Disadvantage (IRSD) quintiles for postcode of residence. The association of socioeconomic disadvantage on sex, age and LHD region adjusted relative rates of antiviral dispensing (aRR) and sex, age, residential aged care facility (RACF) status and LHD region adjusted odds ratios (aOR) for type of antiviral dispensed were calculated.

Results
Antiviral dispensing was greater in females (aRR 1.11, 95% CI 1.09-1.14), metropolitan areas (aRR 1.19 95% CI 1.15-1.23) and in areas of least disadvantage (aRR least v highest 1.39, 95%CI 1.32-1.46). The relative difference in dispensing rate between least and most disadvantaged areas increased significantly over time (p<0.001). Of the 334,232 doses dispensed, 70.3% were molnupiravir and 29.7% were nirmatrelvir/ritonavir. Nirmatrelvir/ritonavir was more likely to be dispensed in the areas of least disadvantage (aOR least v highest 1.89, 95%CI 1.84-1.94).

Conclusions
The association between socioeconomic disadvantage and lower antiviral dispensing highlights the inequity in provision of COVID-19 antivirals. Higher prevalence of contraindicated conditions, reduced access to primary care and cost barriers are likely to be contributing factors. These findings provide valuable evidence to inform public health strategies aimed at ensuring equitable access to antiviral treatments.

Background: Memory B cells (MBC) are effectors of rapid and cross-reactive antibody responses following re-exposure, critical to long-term protection. MBCs comprise of diverse cellular phenotypes that include ‘classical’ (CD21+CD27+) and ‘non-classical’ (CD21LoCD11c+CD27+) subsets. There is little known of the types of MBC induced when different vaccine platforms (adenoviral-vector, mRNA and protein) are combined within a schedule. We characterised SARS-CoV-2-specific MBCs generated by homologous and heterologous combinations of adenoviral-vector, mRNA and protein COVID-19 vaccines in Australian adults enrolled in the Platform Trial in COVID-19 Boosting (PICOBOO).

Methods: Cryopreserved peripheral blood mononuclear cells from a subset of 50-69-year-old PICOBOO participants were assessed. Individuals were primed with either Oxford-Astrazeneca Vaxzevria (AZ; n=55) or Pfizer Comirnaty (Pf; n=59) and subsequently randomised 1:1:1 to receive 4th dose Pf, Moderna Spikevax (Mod) or Novavax Nuvaxovid (Nvx) monovalent ancestral booster. PBMC were analysed using 29-parameter full-spectrum flow cytometry incorporating Ancestral SARS-CoV-2 Spike and Influenza HA (A/Darwin/2021; negative control) tetramers, to assess the antigen-specific MBC response. Vaccine booster arms were compared using the Kruskal-Wallis test.

Results: Computational cytometry analysis of 279,408 antigen-specific B cells yielded 14 phenotypically distinct subsets reactive to SARS-CoV-2-Spike or Influenza HA. In both AZ- and Pf-primed adults, boosting with Pf and Mod resulted in an expansion of Spike-specific non-classical CD21loCD11c+CD27+IgG1+ MBC bearing an activated (CD71hi) phenotype at day 7 and 28 post-boost, which was not observed in Nvx-boosted individuals. In contrast, Nvx generated similar Spike-specific classical MBCs (CD21+CD27+CD45RB+IgG1+) compared to Pf and Mod boosters. IgG4+ MBC frequencies were higher in Pf-primed individuals compared to AZ-primed individuals, irrespective of booster type. MBC subsets specific for the control Influenza HA were similar over all study timepoints and priming schedules.

Conclusion: We demonstrate quantitative differences in the MBC response elicited by both homologous and heterologous COVID-19 vaccination, which have implications in vaccine strategies for COVID-19 and beyond.

Background
Australia achieved 99% coverage for the first two doses of the COVID-19 vaccine among those aged 70 and older in 2022, but uptake of 2023 pre-winter COVID booster vaccinations was lower. Recent COVID-19 vaccination rates are lower among overseas-born individuals and those with limited English proficiency, but no research has identified which specific ethnic groups have the lowest uptake.

Methods
We created a population-based cohort study by linking the Census and the Australian Immunisation Registry to examine COVID vaccination uptake 01/01/2023 to 30/06/2023. The study sample included all those aged 65 years and over who responded to the Census and were still alive and in Australia by the end of the study period (N= 4047320). Ethnicity was based on self-reported ancestry in the Census. We calculated the age-standardised percentage receiving a recent COVID-19 vaccine dose by ethnicity stratified by sex.

Results
Preliminary results found an overall recent vaccination uptake of 44.5% for males and 44.3% for females. However, the recent vaccination rate was 20% or lower in those of North African and Middle Eastern, Central Asian, South Eastern European, Central American and Pasifika ethnicity. There were also important differences by sex. Lower vaccination rates in females tended to be observed in ethnic groups with the lowest overall vaccination rates (12.0-26.6%). In contrast, lower vaccination rates in males were observed in those of Latin American, Caribbean or North American ethnicity who had vaccination rates of 28.4-47.5%.

Conclusions
We found large ethnic inequalities in recent COVID-19 vaccination uptake in older Australians. We also found important intersections between sex and ethnicity in vaccination rates. We will be further exploring intersections with migration-related factors and socioeconomic position in the work. These findings highlight the need for targeted public health strategies that actively engage with priority communities to address these vaccination inequalities.

Background: Despite nearly two decades of high pneumococcal conjugate vaccine (PCV) coverage in Australia, invasive pneumococcal disease (IPD) continues to cause a significant disease burden. The epidemiology of IPD changed with the non-pharmaceutical interventions (NPIs) used to control the coronavirus disease (COVID-19) pandemic. We assessed the impact of these NPIs on viral co-infection rates, serotype distribution, and clinical characteristics of IPD in Australian children before and after NPI implementation.

Methods: We retrospectively reviewed IPD cases in children <18 years at four Australian children’s hospitals, identified via two state reference laboratories, incorporating two-year periods pre- (2017–2018) and post-NPI (2021–2022).

Results: We analysed 220 cases (116 in pre-NPI and 104 in post-NPI cohorts). More than half (n=120) had a viral co-infection, commonly rhinovirus (n=26), RSV (n=21), and influenza (n=7). Children with antecedent or concurrent viral co-infection were younger at the time of IPD presentation (3.4y vs 4.3y, p=0.05), had longer hospital stays (15.3 vs. 10.4 days, p=0.01), and prolonged duration of fever (>14 days; 11% vs. 1%, p=0.04) compared to those without viral co-infection. Serotype 3 was the most frequently identified cause of IPD (25.0%, 44/176), and one-quarter of serotyped cases (25.6%, 45/176) were due to serotypes included in newer PCVs. No significant differences were observed in mean age, fever duration, or markers of inflammation between pre- and post-NPI cohorts. However, a higher proportion of cases presenting with meningitis (3.4% vs 13.5%, p=0.001) was observed post-NPI. Bacteraemia occurred in 25.0% (29/116) of pre-NPI cases and 31.7% (33/104) post-NPI.

Conclusions: Our study reveals unique insights into the changing epidemiology of paediatric IPD in Australia. We highlight the substantial contribution of newer PCVs in covering serotypes causing IPD and the potential role of enhanced immunisation in reducing severe IPD in children with viral co-infections.

COVID-19 disease can result in multi-organ pathologies including autoimmune-like complications, and persistent debilitating post-acute COVID19 sequalae (PASC). Autoantigen arrays for over 103 human proteins identified new autoreactive targets increased post COVID19 present up to 8 months after a single infection. To determine if molecular mimicry was able to drive autoreactivity, we predicted bioinformatically 11 novel B cell-epitopes (12-20 aa long), within human proteins, with potential to be cross-reactive with SARS-CoV-2 and explain aspects of COVID-19 pathology. Plasma or sera collected from cohorts of both COVID-19 negative and convalescent volunteers, from Victoria and Tasmania (n=290), was tested by ELISAs to measure IgG to the SARS-CoV-2 epitopes and their corresponding human protein homologues. Seven new SARS-CoV-2 specific epitopes and six corresponding epitopes in human proteins showed substantial reactivity. Four were significantly elevated post-COVID19. While most individuals responded to either the SARS-CoV-2 or it’s corresponding homologous human protein derived epitope, a percentage (1-27% depending on epitope region) reacted strongly to both. Two novel SARS-CoV-2 epitopes from the Nucleoprotein (NP) were recognised in most of the cohort, regardless of COVID-19 status (>83% positive), indicating potential environmental cross-reactivity. IgG levels to one of these abundant epitopes (NP4) showed a strong correlation (p<0.0001) to a homologous self-epitope in an autoantigen at lower reactivity levels. Given the frequent antibody recognition of the NP4 epitope pre-COVID19 we further tested its potential to cross-react with environmental microbes. We found and validated new NP4 homologous B-cell epitopes in proteins of Pseudomonas and Aeromonas bacterial species. Overall, these studies identify novel B cell epitopes within SARS-COV2 with potential to cross-react with both autoantigens and bacteria, indicating antibody reactivity to SARS-COV2 may be multidimensionally driven and modulated through molecular mimicry to the human host, as well as environmental microbes. These studies may have direct implications for understanding the initiation and persistence of PASC, as well as for the design of next generation vaccines using proteins beyond Spike.

Background: In older adults ≥60 YOA, adjuvanted RSVPreF3 was 82.6% effective against RSV lower respiratory tract disease over 1 season and provided clinically relevant protection over 3 seasons. In adults 50–59 YOA, including those at increased risk (AIR) for RSV, adjuvanted RSVPreF3 induced a non-inferior immune response compared to adults ≥60 YOA. We report immunogenicity and safety of adjuvanted RSVPreF3 in AIR adults 18-49 YOA.

Methods: Phase 3 open-label study (NCT06389487). AIR adults 18–49 YOA (RSV-AIR group) with chronic cardiopulmonary diseases, diabetes mellitus types 1/ 2, chronic liver or renal diseases, neurologic or neuromuscular conditions and older adults ≥60 YOA (RSV-OA group) received 1 dose of adjuvanted RSVPreF3. Non-inferiority of humoral immune response in AIR adults 18–49 YOA versus older adults ≥60 YOA was assessed 1M post-vaccination, with reactogenicity and safety.

Results: 855 participants received adjuvanted RSVPreF3 (RSV-AIR: 426; RSV-OA: 429). 1M post-vaccination, non-inferiority in immune response was shown for RSV-A and RSV-B neutralizing titers. Within 4 days post vaccination, solicited AEs were reported by 91.1% (RSV-AIR) and 70.3% (RSV-OA) of participants, with the most frequent being injection site pain, myalgia, and fatigue. Most solicited AEs were more common in RSV-AIR compared to RSV-OA, but there was low and comparable reporting of grade 3 events across groups. Unsolicited AEs within 30 days post-vaccination were 15.0% (RSV-AIR) and 16.3% (RSV-OA). SAEs up to the data lock point were reported by 0.2% (RSV-AIR) and 1.4% (RSV-OA) of participants, with no vaccine-related SAEs, potential immune-mediated diseases, or deaths.

Conclusions: Adjuvanted RSVPreF3’s immune responses in AIR adults 18–49 YOA were non-inferior to the immune responses in adults ≥60 YOA, in whom efficacy was demonstrated. In AIR adults 18–49 YOA, the adjuvanted RSVPreF3 had a clinically acceptable reactogenicity and overall safety profile.

Funding: GSK (222253); Encore from RSV Symposium