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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: HIV
• Intervention / Treatment: Biological: IM

• Study Type: Interventional
• Enrollment (Estimated): 350
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Wang-Da Liu, M.D., M.P.H.; Phone Number: +886-972-652797; Email: b95401043@ntu.edu.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MF59-adjuvant vaccine	Biological: IM; 0.5ml/Vial, IM on Day1
Active Comparator: high-dose vaccine	Biological: IM; 0.5ml/Vial, IM on Day1
Active Comparator: egg-based vaccine	Biological: IM; 0.5ml/Vial, IM on Day1

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The vaccine response rate among participants undergoing MF59-adjuvanted and high-dose influenza vaccines at day 28	The vaccine response rate among participants undergoing MF59-adjuvanted and high-dose influenza vaccines at day 28, defined as the proportion of patients exhibiting seroconversion for at least 1 viral strain (A/H1N1, A/H3N2, or B) contained in the trivalent vaccines at day 28 after vaccination. Seroconversion was defined as a ≥ 4-fold increase of HAI titer from baseline.	1 month

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): September 1, 2026
• Primary Completion (Estimated): February 28, 2027
• Study Completion (Estimated): December 31, 2028

Study Registration Dates

• First Submitted: June 8, 2026
• First Submitted That Met QC Criteria: June 8, 2026
• First Posted (Actual): June 12, 2026

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 8, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: HIV; vaccine; influenza
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Influenza, Human
• Other Study ID Numbers: 202603137MIPA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No