Background
RZV had >90% efficacy against HZ in ≥50- and ≥70-year-olds (YO) in pivotal trials of ~4- Y follow-up. There is a need to understand long term vaccine efficacy (VE) by age strata. This final analysis of ZOE-LTFU (NCT02723773) provides, for the first time, long-term VE by age strata, plus safety after 11Y of follow-up since vaccination in the ZOE-50/70 efficacy studies (NCT01165177/NCT01165229).

Methods. VE during ZOE-LTFU was assessed overall against HZ in participants vaccinated from age 50 Y (primary objective) and by age ranges. Additionally, VE was assessed from 1 month after the second dose of RZV (RZV2) in ZOE-50/70, and yearly, overall and in all age ranges (secondary objectives). Analysis of VE for ZOE-LTFU used historical control estimates from the ZOE-50/70 placebo groups. Serious adverse events (SAEs) related to vaccination were recorded.

Results. 7258 subjects were included in the VE assessment on modified total vaccinated cohort (mTVC) over the duration of ZOE-LTFU. Overall, during 6 Y follow up in ZOE-LTFU, VE against HZ was 79.77% (95% CI 73.72–84.61) in participants ≥50 Y, and 73.18% (62.94–80.92) in participants ≥70 Y. VE from 1-month post-RZV2 until median of 11.6 Y post-vaccination was 87.73% (95% CI 84.89–90.12) in ≥50 YO and 84.33% (79.91–87.93) in ≥70 YO. Annual VE at Y11 was 82.00% (95% CI 63.03–92.22) in ≥50 YO and 72.00% (33.41–89.77) in ≥70 YO. No SAEs were considered causally related to RZV vaccination by the investigators.

Conclusions. RZV is the only vaccine to demonstrate high efficacy against HZ persisting beyond 10 Y. Uniquely, protection extends to all age-groups vaccinated from age ≥50 Y. No new concerns regarding RZV long-term safety were identified. Study results provide a better understanding of long-term protection with RZV and can guide decision-making regarding vaccination for HZ prevention.

Funding: GSK (201190); Encore from 34th ECCMID 2024

Background: Recombinant zoster vaccine (RZV) is recommended for herpes zoster (HZ) prevention in adults ≥50 YOA, but those with HZ history were excluded from pivotal trials. Final results are presented for a clinical trial evaluating HZ recurrence and safety after RZV vaccination in adults with HZ history.

Methods: This phase III, observer-blind, placebo-controlled trial (NCT04091451) randomized (1:1) adults ≥50 YOA with documented HZ episode ≥6 months prior. Participants received RZV or placebo 2 months apart and were followed for ≥ 26 months. Primary endpoint: HZ incidence from month 3 to study end (non-inferiority: upper limit of 95% CI of incidence rate ratio [IRR] of HZ recurrence [RZV vs. placebo] <5) in modified exposed set (mES: 2 doses, no HZ episode prior to 30 days post-dose 2). Complementary analysis assessed IRR in exposed set (ES: ≥1 dose) from day 1 to study end. Secondary endpoints included: solicited AEs 7 days post-dose, SAEs and potential immune mediated diseases (pIMDs) from day 1 to 1-year post-dose 2, and vaccine-related SAEs until study end.

Results: 1426 adults (RZV: 714; Placebo: 712) received ≥1 dose. All 8 confirmed HZ cases in mES (RZV: 668; Placebo: 682) were in Placebo group. Non-inferiority was met (IRR: 0.00 [95% CI: 0.00–0.46]). Similar results were seen in the ES. Similar results were observed in ES. Most solicited AEs were mild/moderate; median duration: ~2 days. Administration site pain and fatigue were the most common. SAEs were reported by 44 (6.2%) participants in RZV group and 32 (4.5%) in placebo group; pIMDs by 4 (0.6%) and 7 (1.0%) participants, respectively. One SAE/pIMD (type 1 diabetes, onset 701 days post-dose 2) was considered vaccine-related.

Conclusions: In adults ≥50 with a history of HZ, RZV does not increase recurrence and shows no new safety concerns, consistent with its known safety profile.

Funding: GSK (204939); Encore from ESCMID 2025

Background
ZOE-LTFU was an extension of two pivotal efficacy trials (ZOE-50/70) following participants vaccinated with adjuvanted recombinant zoster vaccine (RZV). Vaccine efficacy (VE) against herpes zoster (HZ) from 1-month post-dose 2 up to 11 years was 87.7%. We report characteristics of confirmed HZ cases during ZOE-LTFU, focusing on pain and complications.

Methods
ZOE-LTFU was a phase 3b, open-label study conducted in 18 countries between 2016 and 2023 (NCT02723773). Participants from the original randomised trials (NCT01165177 and NCT01165229) who received ≥1 dose of RZV were eligible. Pain experienced during an HZ episode was evaluated by the Zoster Brief Pain Inventory (ZBPI) until 90 days after first HZ visit or a 4-week pain-free period.

Results
Of 7273 participants in the primary VE analysis cohort, 69 had a confirmed HZ episode, and 61 had a ZBPI evaluation within 16 days of rash onset. Median age at first vaccination was 71.0 (50.0–87.0) years (N=69). Most participants (58/61, 95.1%) reported pain, with 52 (85.2%) experiencing clinically significant pain (score ≥3) and 38 (62.3%) reporting severe pain (score ≥7). Mean Worst Pain Score was 6.7 (standard deviation 3.0). Clinically significant pain resolved after a median of 19 days. Most participants (85.2%) received pain medication with a trend for longer duration of use with increasing age. VE was 87.5% (95% confidence interval [CI] 64.8, 96.8) against post-herpetic neuralgia (PHN) and 91.7% (95% CI 43.7, 99.8) against non-PHN complications in participants ≥50 years; complications occurred in participants ≥76 years 6–10 years after vaccination.

Conclusion
The limited numbers of HZ cases in ZOE-LTFU were associated with less frequent HZ complications. VE against PHN and non-PHN complications remained high over 11 years and was comparable to the original studies. These findings support the long-term benefit of RZV in preventing HZ and its complications.

Funding: GSK (201190); Encore from IDWeek 2024

Reliable estimates of varicella-zoster virus-related disease burden are important for surveillance, burden estimation and vaccine program evaluation. Studies of varicella coding accuracy in Australia are limited. We aimed to validate the primary diagnosis of varicella (ICD-10-AM code B01 subcategories) in a selection of hospital records in New South Wales (NSW).

We undertook a retrospective audit of hospital episodes with a principal diagnosis of varicella between 2017 to 2023, for children and adults at three NSW hospitals. Medical records were reviewed to determine whether an a-priori case definition for varicella or zoster was met. Differences in characteristics of correctly and incorrectly-coded hospital episodes were analysed.

Of 113 included hospital episodes, 69 (61%) met the case definition for varicella, 36 (32%) for zoster, seven (16%) neither varicella nor zoster, and one (2%) could not be determined. Compared to non-varicella cases, varicella cases had a lower mean age (21 ± 18.4 vs 47 ± 20.6, p<0.0001), shorter length-of-stay (median 2-days, IQR:1¬–4-days vs 4.5-days, IQR:3–8.5, p<0.001), shorter antiviral duration (median 8-days, IQR:7¬–10 vs 14-days, IQR:10–15, p<0.0001) and fewer complications (25% vs 64%, p<0.001). Severe complications occurred more frequently amongst non-varicella cases; meningitis (29% v 3%, p<0.001), encephalitis (16% vs 3%, p=0.012) and pneumonia (7% vs 4%, p=0.28).

There is substantial error in coding of hospital episodes using varicella diagnostic codes, potentially impacting burden estimates and vaccine evaluations. Ongoing training of clinicians and medical coders in recording and coding of varicella and zoster in hospital records is required.

Background:
Due to high rates of invasive meningococcal B disease, a 4CMenB vaccine population-based program was introduced in infants in October 2018 and in adolescents in February 2019 in South Australia.

Aim:
This study aimed to evaluate the long-term vaccine effectiveness (VE) and vaccine impact (VI) of 4CMenB on invasive meningococcal disease (IMD) and gonorrhoea, five years after implementation of the program.

Methods:
VE was estimated as the reduction in the odds of IMD and gonorrhoea notifications using a case-control approach. Vaccination history was obtained from the Australian Immunisation Register with 20 matched controls selected for each case. Vaccine impact for both diseases was estimated as incidence rate ratios (IRR) in pre-vs-post-program implementation years using negative Poisson/binomial regression. The instantaneous risk of a second gonococcal notification was assessed using Cox proportional hazards regression.

Results:
For IMD, VE=98.5% (95%CI 81.9-99.9%; p=0.001) for three doses and VE=64.0% (95%CI 7.4%-86.1%; p=0.034) for 2 doses in infants. In adolescents, two-dose VE=92.6% (95%CI 37.5%-99.1%; p=0.017). There was a 72.8% relative reduction in IMD B disease in infants <12 months of age (adjusted IRR=0.272 (95%CI 0.119%-0.622%; p=0.002) and 76.2% reduction in adolescents aged 15-18 years of age (adjusted IRR=0.238 (95%CI 0.097%-0.584%; p=0.002).
Estimated two-dose VE against gonorrhoea in adolescents and young adults was 40.1% (95%CI 32.5%-46.9%; p<0.001) using age-matched individuals with chlamydia notifications as controls. VE=-4.3% (95%CI -41.8-33.2) >60 months post-vaccination compared to those within 3-60 months of vaccination (VE=42.8% (95%CI 35.1%–49.6%)). Females had a higher VE estimate (41.6% (95%CI 31.4%-50.3%)) compared to males (38.9% (95%CI 25.5%-48.3%)). There was a 35.5% relative reduction in gonorrhoea notifications in 15-17 year olds (adjusted IRR=0.645 (95%CI 0.436-0.955; p=0.028)). The risk of a second gonococcal notification was lower in vaccinated gonococcal cases (aHR=0.633 (95%CI 0.465-0.861;p=0.004).

Conclusions:
4CMenB demonstrates high effectiveness against IMD and moderate effectiveness against gonorrhoea up to five years post-vaccination and offers benefit to high-risk groups for both diseases. Waning effectiveness was observed for gonorrhoea at 5 years. Continued evaluation of effectiveness for IMD and requirement for booster doses will occur through the recently NHMRC awarded NEIS Centre of Research Excellence in Neisseria disease control.

Background:
Gonococcal infection notifications have more than doubled over the last decade in Australia. Historically, gonococcal infections have been notified predominantly in men who have sex with men (MSM) and active public health messaging and testing practices have targeted this priority group. Between 2013 and 2021 the ACT has seen a greater than five-fold increase in notifications of cases in females. Given the asymptomatic nature of many of these infections combined with the more severe outcomes for females and persons who are pregnant, the increase in disease in this group is of concern. This study aimed to understand behaviours associated with gonococcal transmission to inform appropriate interventions and health promotion tools to reduce ongoing risks.

Methods:
Since February 2022, the online self-administered Gonococcal Enhanced Case Questionnaire (GECQ) has been distributed to ACT cases with notified gonococcal infection. This descriptive analysis of GECQ data compared differences between MSM and different-sex exposed males and females who completed the questionnaire between February 2022 and January 2025.

Results:
During the study period there were 1356 gonococcal infection notifications in the ACT and 461 responses to the GECQ, including 83 female, 65 men who have sex with women (MSW) and 269 records for MSM. Compared with MSM, a greater proportion of female cases reported having five or fewer sexual partners, meeting partners through friends and face-to-face social settings, and that they likely acquired their infection from a long-term partner. All groups most commonly report using condoms sometimes or never, with less than 15% in any group reporting always using condoms.

Conclusion:
This study shows differences in behaviours between MSM and female cases, particularly in meeting partners, and types of relationships. These differences should be considered when interventions and health promotion tools are designed and implemented.

Background: Emerging evidence indicates that the four-component serogroup B meningococcal (4CMenB) vaccine may offer protection against gonorrhoea due to genetic similarities between Neisseria meningitidis and Neisseria gonorrhoeae. The 4CMenB vaccine was provided for all 14-19 year olds as part of the B Part of it NT study, from March 2021 in the Northern Territory (NT), which has the highest notification rate of gonorrhoea in Australia. Vaccine effectiveness (VE) against gonococcal infection was evaluated three years after commencement of the study.

Methods: We undertook a time-to-event analysis, of all individuals recorded as born in the NT between 1 January 2001-31 December 2009 and gonococcal notifications reported in the NT from 1 March 2021 to 29 February 2024. The Australian Immunisation Register (AIR), a national database recording vaccinations administered to all individuals in Australia, was used to link to gonococcal notifications obtained from the NT Notifiable Disease System. Cox regression analysis was performed to estimate VE, stratifying by age and socio-economic status and adjusting for sex at birth, with time to gonorrhoea notification as the outcome and vaccine status as a time-dependant variable.

Findings: Of 34261 individuals, 42.1% identified as Indigenous, 49.9% resided in low socio-economic areas, 48.1% were female, and 7.9% were fully vaccinated. Of 1308 gonococcal cases, 97.3% occurred in Indigenous young people, 60.6% were in females and 77.9% in people from low socio-economic areas. The incidence of a first notification of gonococcal infection was 0.19 per 10,000 person-years (42 events in 2701 individuals) in the fully vaccinated group and 0.37 per 10,000 person-years (1234 events in 30674 individuals) in the unvaccinated vaccinated group. VE=45% (adjusted Hazard Ratio=0.55 [95% CI 0.40–0.75]; p<0.001).

Interpretation: Based on notification rates, 4CMenB had moderate effectiveness with a reduced risk of gonococcal infection in vaccinated young people. However the analysis did not take account of differential exposure to gonorrhoea risk and to the uptake of diagnostic testing, both of which may differ by vaccination status. A 4CMenB vaccine program has now been introduced in the Northern Territory for infants and adolescents.