Background and Aim: Mucosal antibodies provide a first line of defence against SARS-CoV-2 by limiting viral replication and aiding clearance. Limited data exist on how different vaccine platforms interact within mixed vaccination schedules. We characterised ancestral spike-specific antibodies induced by homologous and heterologous combinations of DNA vector, mRNA, and protein COVID-19 vaccines in Australian adults enrolled in the Platform Trial in COVID-19 Boosting (PICOBOO).


Methods and Analysis: Serum and saliva samples from PICOBOO participants (50–69-year-old) collected at baseline, 1, 3 and 12 months, were assessed for anti-ancestral SARS-CoV-2 Spike IgA and IgG using Mesoscale Discovery. Participants who had been primed with either Oxford-AstraZeneca Vaxzevria (AZ) or Pfizer Comirnaty (Pf) were subsequently randomised 1:1:1 to receive a fourth dose Pf (n=20 AZ-primed:20 Pf-primed), Moderna Spikevax (Mod;n=19 AZ-primed:19 Pf-primed) or Novavax Nuvaxovid monovalent ancestral (Nvx;n=20 AZ-primed:20 Pf-primed) booster.


Outcomes: Salivary IgA, IgG, and serum IgG levels were higher in adults primed with Pf compared to those primed with AZ at baseline, with this difference being maintained to 3-month post-boosting. Seroconversion, indicated by ≥4-fold rise in antibody titre, for salivary IgA was absent at 1-month in the AZ-primed group regardless of booster type, whereas for the Pf-primed group rates were 0/18, 2/18 and 3/19 when boosted with Mod, Nvx or Pf, respectively. The highest rates of seroconversion in serum and salivary IgG at 1-month post-boost were observed in individuals AZ-primed:Mod-boosted (11/19, 11/17 respectively), Pf-primed:Pf-boosted (10/19, 8/19), Pf-primed;Nvx-boosted (9/19, 7/18), AZ-primed:Pf-boosted (7/20, 8/18), Pf-primed:Mod-boosted (4/17, 5/18), and AZ-primed:Nvx-boosted (0/18, 3/19).


Conclusions and Future Actions: COVID-19 booster vaccines induce limited mucosal IgA responses, regardless of priming or booster regimen. In contrast, serum and salivary IgG may vary with vaccine schedule, with IgG transfer into saliva potentially contributing to protection. These findings underscore the need to define optimal heterologous booster strategies for mucosal immunity in future vaccination programs.

BACKGROUND & AIM: Avian influenza H5N1 and its genetic reassortants are highly pathogenic viruses with potential to infect humans, posing a global threat due to lack of immunity. Two MF59-adjuvanted, cell culture–derived H5 vaccines (aH5N8c; aH5N6c) are part of USA’s pandemic stockpile. This study assessed the safety of a homologous and heterologous prime-boost regimen with aH5N8c or aH5N6c in adults.

METHODS & ANALYSIS: In a Phase 2, randomized, observer-blind, multicenter study, 479 adults (18–64 years, n=240; ≥65 years, n=239) were randomized 2:1:1 to three priming regimens on Days 1 and 22: Arm A, two doses of aH5N8c (n=239) [homologous priming]; Arm B, aH5N8c→aH5N6c (n=120) [heterologous priming]; Arm C, aH5N6c→aH5N8c (n=120) [heterologous priming]. All subjects received aH5N8c on Day 202 (6 months post-2nd priming). Safety endpoints included solicited local/systemic adverse events (AEs), unsolicited AEs, serious AEs (SAEs), AEs of special interest (AESI), AEs leading to study withdrawal, and medically attended AEs (MAAEs). Data were analyzed by vaccination and age cohort.

OUTCOMES: Solicited and unsolicited AEs rates: comparable among groups. Most solicited AEs (up to 7 days post-vaccination): mild/moderate, occurred soon after vaccination, resolved within 3 days. Solicited AE rates after second priming and booster vaccinations: similar or lower than after the first dose. Solicited AEs: reported by fewer older adults than 18–64 years. The most frequent solicited local AE and systemic AE was injection site pain and fatigue respectively. Related unsolicited AEs (up to 3 weeks post-vaccination): low. MAAEs occurred in 36.7–45.8% subjects over 12 months, with no related SAEs, AESIs, or deaths. One subject each from Arms A and B withdrew due to an AE.

CONCLUSION AND FUTURE ACTIONS: Multiple vaccinations with MF59-adjuvanted H5 vaccines demonstrated an acceptable safety profile. Solicited AEs were common, transient and mild/moderate, with lower reactogenicity in older adults. Rates did not increase after subsequent doses.

Background: The highly pathogenic avian influenza H5N1 subtype and its genetic reassortants pose a global threat due to their ability to infect humans and the lack of immunity to H5 viruses in humans. We evaluated prime-boost regimens comprising two MF59-adjuvanted, cell-culture–derived vaccines containing either H5N8 A/Astrakhan/3212/2020 (aH5N8c) or H5N6 A/Guangdong/18SF020/2018 (aH5N6c). Primary immunogenicity (Days 1–43) and safety results are presented separately.

Methods: This Phase 2, randomized, observer-blind study assessed the immunogenicity of an aH5N8c booster administered 6 months after homologous or heterologous priming in 479 adults. Participants received two priming doses on Days 1 and 22: Arm A, aH5N8c→aH5N8c (n=239) [homologous priming]; Arm B, aH5N8c→aH5N6c (n=120) [heterologous priming]; Arm C, aH5N6c→aH5N8c (n=120) [heterologous priming]. All received aH5N8c booster on Day 202. Assessed at Day 223 (3 weeks post-booster): Hemagglutination inhibition (HI) and microneutralization (MN) responses against H5N8. Also assessed on Day 209 (7 days post-booster) and Day 382 (6 months post-booster): HI responses.

Results: 7 days post-aH5N8c-booster, robust antibody responses were observed: HI geometric mean fold increases (GMFIs) were 4.1, 7.1, 4.9 in Arms A–C, respectively. HI titers continued to rise, with Day 223/Day 202 HI GMFIs of 5.4, 10.7, 6.4, in Arms A–C, respectively. Day 223/202 HI seroconversion rates (SCRs) ranged from 57.7%-73.5%. Subjects with HI titer ≥1:40 ranged from 82.3%-86.9%. Day 223/Day 202 MN GMFIs were 8.4, 18.7, 12.0 in Arms A–C, respectively, with SCRs from 79.6-85.9%; MN titers ≥1:40 from 91.4% to 93.8%. Responses persisted 6 months post-booster. Both age cohorts (18-64 years and ≥65 years) had robust responses, though HI SCRs and MN SCRs were higher in younger adults.

Conclusions: A single aH5N8c booster given 6 months after priming elicited rapid, robust immune responses across all regimens and age cohorts, supporting its role in pandemic preparedness for H5 influenza viruses.

BACKGROUND & AIM: Increasing transmission of avian influenza H5N1 from wildlife/livestock to humans poses a global threat due to limited population immunity. We assessed immunogenicity of two doses of MF59-adjuvanted, cell-culture–derived H5N8 A/Astrakhan/3212/2020 influenza vaccine (aH5N8c). Booster immunogenicity at 6 months and safety results are reported separately.

METHODS: This Phase 2, randomized, observer-blind, multicenter study enrolled 479 subjects, 239 received two doses of aH5N8c. Participants included: 121 aged 18–64 years (60 poultry workers); 118 aged ≥65 years. Serum samples at baseline (Day 1), Day 22, and Day 43 assessed antibody responses via hemagglutination inhibition (HI) and microneutralization (MN) assays. Primary endpoints: HI and MN responses against H5N8 at Day 43. ANALYSES: geometric mean titers (GMTs), geometric mean fold increases (GMFIs), seroconversion rates (SCRs), percentages achieving titers ≥1:40. Subgroup analyses considered age, poultry worker status, prior influenza vaccination, sex, race.

OUTCOMES: After the first dose, HI titers increased, with GMFIs of 3.8 (18–64 years) and 5.6 (≥65 years) at Day 22. After the second dose, HI titers still rose, reaching GMFIs of: 13.7 (younger adults); 10.2 (older adults) at Day 43. SCRs were 75.8% (younger adults) and 71.0% (older adults); percentages achieving HI titers ≥1:40 were 75.8% and 73.0%, respectively. MN titers assessed in a subset: generally higher than HI titers, showing robust antibody responses across age cohorts at Day 43. MN GMTs exceeded HI GMTs, with Day 43 MN GMTs of 157.6 (younger adults) and 141.3 (older adults). MN SCRs reached 80.6% (younger adults) and 70.0% (older adults). No notable differences in immune responses by subgroup; baseline titers were uniformly low.

CONCLUSION; FUTURE ACTIONS: Two doses of aH5N8c three weeks apart elicited strong antibody responses by Day 43. Responses were consistent across age cohorts/subgroups. These findings support MF59-adjuvanted cell-based influenza vaccines as an important public health tool against H5 influenza.

Background and Aim: Immunocompromised (IC) adults with lung or kidney transplant are at increased risk of RSV disease and typically show reduced post-vaccination immune responses. We present immunogenicity and safety of adjuvanted RSVPreF3 in IC vs non-IC adults up to 12 months (M) post-vaccination.

Methods and Analysis: In this open label, phase 2b trial (NCT05921903), lung or kidney transplant recipients aged ≥18 years, randomised 1:1, received 1 adjuvanted RSVPreF3 dose (IC1) or 2 doses 1─2M apart (IC2). Non-IC adults aged ≥50 years received 1 dose. Humoral immune responses (all groups), cellular immune responses (subset), and safety profile were assessed.

Outcomes: Overall, 386 participants received 1-2 doses of adjuvanted RSVPreF3 (IC1: 131, IC2: 130, non-IC: 125). Mean age was 62.4 (±8.7) years; 56% were male. RSV-A/-B neutralising titres increased post-dose 1, further increasing post-dose 2 (IC2). Titres declined over time in all 3 groups but remained above baseline up to 12M post-vaccination. Post-dose 1 neutralising titres were lower in IC adults on mycophenolate (77%) than in IC adults not on mycophenolate and non-IC adults. However, post-dose 2, neutralising titres increased to levels similar to non-IC adults, following the same trend up to 12M post-vaccination. Cellular immune responses (CD4+ T cell frequencies) were high and similar between IC and non-IC adults and remained above baseline up to 12M post-vaccination. Most solicited events were reported at similar rates between IC and non-IC adults. Unsolicited adverse events (AEs) observed post-dose 1 and 2 were overall comparable across groups. Serious AEs were more frequent in IC vs non-IC adults, as expected. No cases of demyelinating disorders, such as Guillain-Barré syndrome, were reported.

Conclusions and Future actions: Adjuvanted RSVPreF3 elicited humoral and cellular immune responses post-vaccination with an acceptable reactogenicity and safety profile in IC adults with lung and kidney transplant.

Encore from ESCMID 2026.

Recently there has been a rapid acceleration in the development of vaccines and long-acting monoclonal antibodies to protect against Respiratory Syncytial Virus (RSV). Progression through the clinical trial pipeline is predicated on a rise in antibody titres, and the assumption that such a rise will lead to a concomitant improvement in protection. Despite this, no accepted immunological correlate of protection exists for RSV. Although several studies report on correlations within a single cohort, there is no established association between antibody titres and protection from RSV across different products and populations. Such a correlate would greatly aid future vaccine development and licensure.

We conducted a systematic review to identify published reports of immunogenicity and/or efficacy in RSV vaccines or long-acting monoclonal antibodies. We identified 130 unique reports, which we compiled into a publicly available evidence map.

We performed a meta-analysis on extracted data to identify if there is a relationship between antibody increase and protection against RSV disease. We found a strong correlation between the immunisation-induced rise in neutralising antibody titres and efficacy (Spearman ρ>0.7 for all comparisons).

For infants, we estimated that each 10-fold increase in neutralising antibody titres provides an additional 31% [95% CI 10%–47%], 47% [95% CI 36%–56%] and 57% [95% CI 45%–66%] reduction in the relative risk of symptomatic, moderate and severe disease, respectively. For older adults, a 10-fold rise in antibody levels was associated with a 34% [95% CI -2%–57%], 50% [95% CI 22%–67%] and 63% [95% CI 36%–79%] reduction in the relative risk of RSV disease with 1, 2 and 3 symptoms, respectively.

The correlate identified through our meta-analysis aligns closely with evidence from existing therapeutics (e.g. palivizumab), natural history studies and product-specific correlate analyses, supporting its utility in informing vaccine approval and public health policy decisions.

Background and aim
PICOBOO is a randomised, adaptive trial assessing the immunogenicity and reactogenicity of licensed COVID 19 booster vaccines in immunocompetent individuals aged ≥12 years. Our aim was to compare immune responses and safety profiles across nine licensed booster vaccines in adults within strata defined by age and primary COVID 19 vaccine schedule.

Methods and analysis
Between March 2023 and September 2024, healthy participants were enrolled at sites in Perth, Adelaide and Launceston and received one or more randomised booster doses. Anti spike immunoglobulin was measured at days 7, 28 and 84 (or 180), with neutralisation assays performed in a predefined subset. Immunological analyses used a Bayesian three level hierarchical linear model to incorporate shared information across dose number, age groups and mRNA vaccine platforms. Reactogenicity, adverse events, post randomisation SARS CoV 2 infections, hospitalisations and time away from regular activities were captured as unadjusted summary statistics (medians [IQR] and n [%]). Participants were followed to day 720.

Outcomes
A total of 586 adults contributed data for 1,050 booster doses; 57%, 16%, 17% and 10% were randomised once, twice, three or four times, respectively. All booster vaccines increased humoral immunity, with total Ig and neutralisation titres increasing at day 28 and returning to near baseline by day 365. Local reactions occurred after 786 (75%) of vaccine doses and systemic reactions after 798 (76%) of vaccine doses, with 1% local and 5% systemic reactions classified as severe, respectively. Findings are interpreted within the context of pandemic era policy decisions.

Conclusions and future actions
All vaccines generated strong humoral responses with acceptable reactogenicity, supporting ongoing transition to boosters targeting circulating subvariants.