Background: Japanese encephalitis virus (JEV) caused 45 human cases and 7 deaths on mainland Australia in 2021-22(1) and has resurged since December 2024(2). Live-attenuated chimeric (Imojev®) and inactivated (JEspect®) vaccines are available. The JEVID-2 study evaluated immunogenicity and safety of fractional intradermal (ID) Imojev® in comparison with subcutaneous (SC) administration.

Methods: JEVID-2 was a randomised controlled trial of single-dose ID (0.1 mL) versus SC (0.5 mL) Imojev® in healthy, non-pregnant individuals aged ≥5 years in rural New South Wales. Plaque reduction neutralisation serum antibody titres (PRNT50 using JEV Nakayama strain) were performed before, and 1 week, 1 month, and 6 months after, immunisation. Seroconversion was defined as PRNT50 ≥ 1:10 at one month if seronegative at baseline, or a ≥ 4-fold rise in titre if seropositive at baseline.

Results: 236 eligible participants, median age 63 (IQR 50-70), were vaccinated (SC n= 120; ID n=116). One-month seroconversion rates were non-inferior ID (96.5% [95% CI: 91.2%, 99.0%]) compared with SC (99.2% [95.4%, 100.0%]); difference -2.7% [-7.3%, 1.9%].(3)

Overall JEV seropositivity after 6-months was 95.6%, with no significant difference between ID (97.3% [92.0%, 97.9%]) and SC (94% [88.0%, 97.5%]); difference 3.3% [-2.9%, 9.5%]. From >1 to ≤6 months of follow up, 11 serious adverse events occurred; none was considered vaccine-related.

Conclusion: ID administration of Imojev® remains non-inferior to SC in terms of seroprotection at 6-months. Intradermal administration may be a suitable dose- and cost-saving strategy during the current JEV resurgence in Australia and in other endemic settings.

References:

1. Kelly, Paul (Chief Medical Officer of Australia). Statement on the end of the Japanese encephalitis virus emergency response. https://www.health.gov.au/news/statement-on-the-end-of-japanese-encephalitis-virus-emergency-response Published 16 June 2023. Accessed 2 June 2024.

2. National Communicable Disease Surveillance Dashboard, National Notifiable Disease Surveillance System https://nindss.health.gov.au/pbi-dashboard/ Accessed 27 February 2025

3. One-month data presented ASID Canberra Apr 2025.

Background: The Live Attenuated Influenza Vaccine (LAIV) has been widely used in paediatric immunisation programmes in the Northern Hemisphere.We evaluated real-world absolute vaccine effectiveness (aVE) and relative vaccine effectiveness (rVE) of LAIV and Inactivated Influenza Vaccines (IIV) over the 20yrs of LAIV availability.
Methods: SLR and NMA of case-control, test-negative design and cohort studies published from Jan_2003 to Dec_2023 in peer-reviewed journals or by public health institutes. Inclusion criteria: children ≤19yrs in Northern Hemisphere, evaluating seasonal trivalent or quadrivalent LAIV or IIV (standard dose, non-adjuvanted), estimating effectiveness against influenza defined via clinician diagnosis or laboratory-confirmation in any setting. Studies combining multiple influenza vaccines were classified as LAIV or IIV when >90% of the children received LAIV or IIV. Random-effects meta-analysis was used to estimate pooled aVE by season (excluding 2009/10 due to A(H1N1) pandemic) and time period: pre-A(H1N1)-pandemic [2003/04 to 2008/09]; post-A(H1N1)-pandemic and prior to changes to the LAIV strain development process [2010/11 to 2016/17]; and recent years [2017/18 to 2022/23]. rVE was estimated using a three-node NMA (LAIV, IIV and unvaccinated).
Results: All but 3 of the 109 studies defined outcomes using laboratory-confirmation. aVE of LAIV and IIV against any influenza was similar (~50%) across time periods. rVE of LAIV vs IIV was not estimable pre-A(H1N1)-pandemic . From 2010/11, the 95% CIs of rVE overlapped 0 for all influenza outcomes, with the exception of A(H1N1) from 2010/11 to 2016/17 (-46%,95%CI:-57, -33) and for influenza B in recent years from 2017/18 (196%,95%CI:73, 406).
Conclusions: Over a 20yr period, aVE of LAIV against influenza in the real-world was moderate and comparable to that of IIV. Post-A(H1N1) pandemic, protection of LAIV against A(H1N1) was reduced compared to IIV, but was restored from 2017/18 after updates to LAIV strain development process. LAIV provided greater protection against influenza B than IIV.

Understanding the balance of immune-stimulatory and immune-suppressive antigen specific responses to SARS-CoV-2 antigens is crucial for gaining insight into COVID19 pathology, as well as for designing effective vaccine strategies. T cell responses to the SARS-CoV-2 Spike protein have proven to be long-lasting and protective in some human vaccine clinical trials. The Enzyme Linked Immuno Spot (ELISpot) assay is a powerful and sensitive tool to study antigen specific functional T cell responses. By using the Fluorospot method of the ELISpot, which incorporates multiple fluorescent readouts, we can not only assess individual T cell reactivity but also distinguish between immune-stimulating and immune-modulatory or suppressive responses by simultaneously measuring IFN-γ and IL-10. Preference for IFN-γ or IL-10 induction to Spike antigens could affect the overall strength, and protective potential, of vaccine induced responses. T cell responses to Spike ancestral and variant peptide pools (including novel and cross-reactive T cell epitope regions) were optimised in healthy blood donors using duo-colour Fluorospot assay. Donor specific IFN-γ responses were observed to both CD8 and CD4 peptide pools. Surprisingly, there was a preferential IL-10 induction to specific CD4 T cell epitopes within the pools, suggesting an intrinsically immunosuppressive bias. Immunogenicity to Spike peptide pools were optimised in healthy blood bank donors, and further studies will examine vaccine induced T cell responses in the Platform Trial In COVID-19 vaccine BOOsting clinical trial (PICOBOO), which aims to evaluate the effectiveness, safety, reactogenicity and immunogenicity of different booster vaccination strategies against SARS-CoV-2 ancestral and variant strains in the Australian population. Understanding the vaccine induced immune response to optimised SARS-CoV-2 Spike peptide epitope pools, with an intrinsic biological IFN-γ or IL-10 induction bias, will further our knowledge of antigen-specific and cross-reactive immune-modulation by SARS-CoV-2 antigens and help inform future booster vaccination strategies.

Introduction
SARS-COV-2 anti-spike and anti-nucleocapsid antibody assays are central to COVID-19 vaccine development, surveillance, and policymaking. It is important to assess relative performance between different assays to ensure consistent reliable measurements of antibody response. This study evaluates the concordance of commercially available assays.

Methods
We compared two anti-spike antibody (Anti-S) assays using 1741 paired samples: MesoScale Discovery (MSD) V-PLEX SARS-CoV-2 Panel 29 and Elecsys® Anti-SARS-CoV-2 S (Roche Diagnostics); and two anti-nucleocapsid antibody (Anti-N) assays using 92 samples: MSD COVID-19 Respiratory Panel 2 and Elecsys® Anti-SARS-CoV-2 N.
Samples were obtained from PICOBOO randomised adapative trial (ACTRN12622000238774) participants >18 years-old receiving their 3rd, 4th or 5th COVID-19 vaccine (Pfizer, Moderna, or Novavax) between March 2022-May 2023. Serum was collected pre-randomisation, 1w, 1m, 6m, and 1y post-vaccination.

Deming regression and Pearson’s correlation measured concordance. Geometric mean ratios and Bland-Altman plots estimated differences in titres.

Results
The Anti-S titres from Elecsys® were 6.91-fold (95%CI 6.21-7.68) higher than MSD. This difference was largest at 7 days (GMR 8.20, 95%CI 6.39-10.53) and 1 month (GMR 7.02, 95%CI 6.04-8.17) when mean titres were highest. Both assays were highly correlated overall (r 0.92; slope 1.092, 95%CI 1.071-1.113) and across all timepoints.

The Anti-N titres from Elecsys® were lower than MSD (GMR 0.18; 95%CI 0.09-0.35), but this difference diminished as mean titres increased. For lower antibody levels, MSD detected a wider range of values compared to Elecsys®. The Anti-N assays were less correlated (r 0.68; slope 1.48, 95%CI 1.12-1.85) than the Anti-S assays.

Conclusion
The Anti-S assays were strongly correlated, while the Anti-N assays were less concordant. Both comparisons showed constant and proportional titre differences which may be attributed to varied methodologies, cross-reactivity, or higher sensitivity of the MSD assay. This highlights the need for standardisation of SARS-COV-2 assays to enable serologic data harmonisation at a population level.

Introduction
A highly functional clinical laboratory is critical for supporting quality vaccine research. Multi-centre trials require efficient systems to facilitate reproducible collection, processing and preservation of bio-specimens. We share key lessons about optimising efficiency, capacity, and quality control processes for optimal sample collection in multi-site clinical trials, from the Platform Trial In COVID-19 Priming and Boosting (PICOBOO), a randomised adaptive platform trial, conducted at three Australian sites, involving >50 staff and enrolling 1112 participants, with 70,000 bio-banked specimens collected Mar 2022 to Sep 2024.

Key Learnings
1. Efficiency
The high volume of bio-specimens including sera, saliva and peripheral blood mononuclear cells, relative to available technicians posed a major challenge at trial onset, threatening feasibility. Our laboratory structure allowed senior scientists to discuss and implement swift changes to laboratory protocols with investigators. This resulted in updated processing methods with improved efficiency to cope with high volumes of samples, whilst reducing labour and consumable costs by approximately 20%, saving ~$155,000.

2. Reactive Capacity
Surges in clinic visits and evening collections were often unpredictable posing another major challenge. To optimise the laboratories capacity, we implemented systems involving robust laboratory management, effective methods of communication, and recruitment of surge personnel to staff the laboratory at short notice. This enabled rapid decision-making, scalability, and adaptability to accommodate unforeseen increased laboratory requirements.

3. Quality
Centralised standard operating procedures (SOPs) for sample management ensured consistent quality, integrity, and traceability across sites. Electronic freezer inventories, sample tracking systems, and frequent quality reviews reduced errors, improved documentation accuracy, and maintained bio-specimen quality. SOPs were codeveloped with stakeholders ensuring alignment with trial objectives and downstream immunological testing, ensuring quality and consistency across sites.

Conclusion
These key lessons, essential for optimising laboratory operations, were critical to the success of PICOBOO and systems established will be applicable for future, multi-centre clinical trials.

Our vision is to establish ADAPTIVAX – an investigator-led national adaptive platform for evaluating the comparative immunogenicity, reactogenicity, +/- effectiveness (including cost) of different immunisation strategies targeting preventable disease(s). We will build on existing collaborations and infrastructure established from the MRFF funded Adaptive Platform Trial In COVID-19 BOOsting (PICOBOO) trial (2014690/2016473) to establish a platform to allow the coordination of large-scale, high-impact vaccine trials. ADAPTIVAX will address key priorities of consumers and policymakers and will generate evidence to inform safe, effective, and value-informed immunisation strategies, including for high-risk populations, across the lifespan. These groups will include children, immunocompromised individuals, Aboriginal and Torres Strait Islander people, pregnant women, the elderly and culturally and linguistically diverse populations. Trials will be equitably integrated into healthcare systems and service delivery where possible to optimise research efficiency and to enable inclusion of high-risk populations across jurisdictions and diverse healthcare settings. Research nested within this platform will be prioritised and overseen by an independent scientific steering committee with input from the National Consumer Advisory Group for Vaccine Trials (chaired by CI Hughes) and the National Aboriginal Advisory Group for Vaccine Trials (chaired by CI Crooks). We will discuss key enablers for achieving this vision which will include (i) a governance framework designed to foster multi-institutional collaboration and shared access to central resources, opportunities and academic credit; (ii) collaboration with all end-users of clinical trial evidence including industry partners and (iii) enabling research infrastructure. We will also present the first two proposed research domains, which comprise an evaluation of different (i) pneumococcal vaccination strategies across the lifespan and (ii) immunisation strategies to optimise protection from respiratory syncytial virus (RSV) for mothers and their infants.

Background
BPZE1, a live attenuated intranasal pertussis vaccine, is designed to prevent Bordetella pertussis (Bp) infection (colonization), disease and transmission to address limitations of current vaccines. BPZE1 protects adults, primed with whole-cell pertussis vaccine in infancy, from colonization with virulent Bp. This study assessed BPZE1-induced immune responses, non-interference and safety when administered with or without tetanus-diphtheria-acellular-pertussis vaccine (Tdap; Boostrix™) in children 6-17 years old, primed in infancy with acellular pertussis vaccine (aPV).

Methods
366 healthy school-age participants were vaccinated after randomization 1:1:1 to 109 colony-forming-units (CFU) BPZE1+intramuscular-placebo, 109CFU BPZE1+Tdap, or Tdap+intranasal-placebo. Primary endpoints were geometric mean fold rise (GMFR) from baseline of nasal secretory immunoglobulin A (S-IgA) against whole cell B. pertussis extract (WCE) in BPZE1 and BPZE1+Tdap groups at Day 29 and solicited adverse events (AEs) through 7 days after vaccination. Key secondary endpoint was BPZE1+Tdap induction of serum IgG against tetanus, diphtheria, and aPV antigens compared with Tdap at Day 29.

Results
GMFRs of S-IgA against WCE were similar among BPZE1 and BPZE1+Tdap groups (3.8 [95% CI 3.1-4.7] and 3.5 [2.9-4.3]), but low in Tdap group (1.2 [1.0-1.5]). All participants in BPZE1+Tdap and Tdap groups had anti-tetanus and anti-diphtheria antibody levels ≥0.1 IU/mL and similar serum IgG responses to pertactin, filamentous hemagglutinin and pertussis toxin at Day 29. Solicited AEs were 50%, 52%, 45% (nasal/respiratory) and 42%, 50%, 55% (systemic) in BPZE1, BPZE1+Tdap and Tdap groups, respectively. Unsolicited AEs were similar between groups, no participants discontinued due to AEs, and no serious AEs were related to vaccination.

Conclusions
Intranasal BPZE1 vaccination with or without Tdap induced robust nasal mucosal and non-interfering systemic immune responses in school-age children who had been primed with aPV as infants with a favorable safety profile. In contrast to Tdap, BPZE1 has the potential to both protect against Bp colonization and reduce Bp transmission.

Background
The effectiveness of SMS reminders for improving childhood vaccine coverage and timeliness has varied in previous studies. We developed novel informatics infrastructure to support a digitally-automated trial that evaluated the effectiveness of a range of SMS reminder strategies for improving on-time vaccination in children at GP clinics across Australia.

Methods
AuTOMATIC was a Bayesian adaptive multi-centre randomised trial comparing 12 alternative SMS strategies and a control (no SMS) strategy. SMS arms varied by framing of content (neutral, personal benefit, personal harm or societal benefit) and timing (14 days prior to the due date, on the due date, or 7 days afterwards). Participants were parents of children (<4 years) registered with one of 20 primary care clinics across Australia. The trial primary endpoint was on-time vaccination defined as documented vaccination within 28 days of the due date. The trial used complex coded logic for trial procedures and response adaptive randomisation, allowing the study to be largely automated through practice IT systems.

Results
9,993 parents were randomised and included in the primary analysis; 637 were assigned to control and between 380 and 1,110 to each of the 12 SMS reminder arms. The adjusted odds ratio (aOR) of on-time vaccination for each of the 12 SMS arms compared to control ranged from 1.02 [95% CrI 0.76 to 1.34] to 1.53 [1.22 to 1.92] with a pooled effect aOR of 1.29 [1.06, 1.55]. On average, SMS reminders resulted in a 2% to 11% absolute increment in on-time vaccination compared to no SMS.

Conclusion
SMS reminders improved timely childhood vaccination compared to no SMS but there was no evidence that any content framing or timing option was superior. This trial demonstrates that trial automation is possible without impacting efficacy and may support other future automation for patient communication or nudge interventions.

In the prevention of the childhood diseases and mortality, it is globally recognized that childhood immunization is the most effective strategy (Whitney et al., 2014). Supervising the immunization program by Nursing Leaders is important, to know the effectiveness of the program (Dennison et al., 1968). This research aims to find out the acceptability of the Supportive Supervision E-Tool by Nursing Managers and acceptance by nurses being assessed using the tool. In the health sector, E-tool has become an increasingly key consideration in the development, evaluation and implementation of healthcare interventions (Sekhon et al., 2017).
An explorative mixed method study will be conducted, with the purposeful sampling of supervisors, who will be given a questionnaire, to assess them using the E- tool. While focus group discussions will be conducted with nurses chosen randomly from the divisions on their experience of being assessed with the E-Tool. The discussions were recorded into a voice recorder, data coded, sorted, and categorized into themes as thematic analysis was used.
Expected result would be that the Supervisors would find the E-Tool convenient to use and efficient as it covers all areas of Expanded Program of Immunization (EPI), hence tranquil flow of data and information collected. The tool will also generate the areas the nurse’s should improve on thus creating a more informed feedback sessions. At the same time the managers would comment on questions which may not be clear and suggest changes to be done with the E-tool Questionnaire. From the Nurses they will also be receptive, as the tool will give them Feedback on where to improve, identify tools and equipment’s which are standard to have in his or her facility to effectively carry out the EPI program.
Overall the use of E-Tool has strengthened the supportive supervision through identifying and addressing areas of improvement and a tool which is used by both the supervisors and the workers working together to achieve the expected outcome( Husband, R. (2017), standardizing equipment’s and tools used by health facilities, leading to a better service delivery and outcome. Therefore the use of E-Tool was received and implemented with positivity.

Background: Young people are at heightened risk of new HIV infection in sub-Saharan Africa including Ethiopia. However, few test for HIV because of a range of obstacles including societal stigma and discrimination and inaccessible services. HIV self-testing (HIVST) is a newly endorsed screening test option that seeks to address those challenges. We conducted a qualitative study that explored perspectives of various stakeholders on the acceptability and use of HIVST in Southern Ethiopia, to identify potential enablers and barriers to HIVST.
Methods: A descriptive qualitative study was applied among young people aged 15-24 years, health professionals, peer navigators (lay people trained on HIVST) and HIV program managers . Eight focus group discussions and 15 key informant interviews were completed with a total of 80 participants. Data was analysed using thematic analysis and trustworthiness was assured based on credibility, transferability, dependability, and confirmability criteria of the research technique and reflectivity of the investigatory team.
Results: All the stakeholders reported that HIVST is highly acceptable for young people. Greater privacy and confidentiality and subsequent reduction in stigma and discrimination; increased pathways to confirmatory testing and improved HIV care; reduced risk of contamination to health professionals and clients; and saving time and money were the key enablers identified. Nonetheless, concerns about lack of awareness; fear of social harm; requirement for confirmatory testing; perceived uncertainty and untimeliness; lack and costliness of kits; perceived inaccuracy of oral HIVST; and risk of contamination and pain after blood samples-based HIVST were shared among the stakeholders as barriers.
Conclusions and recommendations: HIVST is a well-accepted HIV screening for young people in urban southern Ethiopia. Interventions aimed to scale up HIVST need to consider barriers and consider wide promotion of the kits through a range of avenues, education on the benefits of HIVST and ways to link people to counselling.