Immunogenicity of MF59-adjuvanted Versus High-dose Influenza Vaccine in People With HIV: a Randomized Clinical Trial

Overview

Seasonal influenza causes morbidity in people with impaired immunity, including adults with elder ages and other comorbidities \[1\]. Standard-dose inactivated influenza vaccines (IIV) may induce lower hemagglutination inhibition (HAI) titers and more rapid waning in these groups. High-dose IIV could generate higher and more durable serological responses, including HAI, B-cell activation and antibody magnitude, which was demonstrated in randomized trials \[2,3\]. MF59-adjuvanted IIV further enhances innate immune activation and antigen presentation, potentially broadening and strengthening responses, particularly during antigenic drift seasons \[4\]. These enhanced platforms represent biologically distinct strategies to overcome reduced vaccine responsiveness. Influenza A/H3N2 was reported as the predominant circulating strain in Taiwan. Initial antigenic characterization suggested suboptimal match between some circulating A/H3N2 viruses (the subclade K variant) and the vaccine reference strain, whereas A/H1N1 viruses appeared consistency with the circulating and vaccine-containing strain \[5\]. As of February 2026, approximately 2,300 cases of severe influenza had been confirmed during the 2025-2026 season, representing the largest epidemic in the post-COVID-19 era. In the meanwhile, both MF59-adjuvanted and high-dose influenza vaccine were firstly introduced in Taiwan for elderly people \[5\]. Previous study had demonstrated that people living HIV (PWH) might have lower humoral immune responses compared with people without HIV, even among PWH with relatively higher (defined as ≥ 350 cells/mm3) CD4 counts \[6\]. In spite of the broad use of these novel influenza vaccines in older adults and other population with immunocompromised status such as the recipient of solid organ transplantation \[7\], evidence gap exists in PWH, where vaccine responses vary by CD4 count, viral suppression, immune activation, comorbidities, and prior vaccination history. High-dose influenza vaccination has shown improved serologic outcomes versus standard dose in PWH in randomized trials \[2\], while data of MF59-adjuvanted vaccines used for PWH are lacking. Moreover, comparative serological responses, durability or effectiveness between the two vaccines (MF59 adjuvant vs high-dose) was only conducted among participants with elder age, which showed that the seroconversion rate for H3N2 among those receiving MF59-adjuvanted vaccines did not meet noninferiority criteria compared with those receiving high-dose vaccines \[8\]. Nevertheless, such data on PWH remains unclear. In this study, we aimed to compare toe immunogenicity among PWH undergoing MF59-adjuvanted or high-dose seasonal influenza vaccine.

Interventions

• Biological IM
  0.5ml/Vial, IM on Day1

Primary outcome measures

• The vaccine response rate among participants undergoing MF59-adjuvanted and high-dose influenza vaccines at day 28 [Time frame: 1 month]

Eligibility criteria

Inclusion criteria

• PWH aged ≥18 years

Exclusion criteria

• History of confirmed severe adverse effects owing to any type of influenza vaccine, including anaphylaxis and Guillain-Barré syndrome.
• Severe coagulopathy which causes contraindication for vaccination.
• Already vaccinated with any type of 2026-2027 influenza vaccines.
• Having diagnosed with influenza one month before vaccination.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT07644546 · 202603137MIPA

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗