Papilloguard with AS04 shows non-inferior immunogenicity to Gardasil in HPV vaccine trialTrial Shows Papilloguard Vaccine Provides Strong Protection Against HPV Infection

Human vaccines & immunotherapeutics Published August 13, 2026 Study authors: Mardani Masoud, Darazam Ilad Alavi, Moini Ashraf, Ebrahimi Ali, Mirhassani Reihaneh, Barati Saghar, … PubMed ↗ DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

AI-generated summary of the cited source, checked by automated accuracy review. How we work

Key Takeaway

Consider Papilloguard as a non-inferior alternative to Gardasil, but interpret higher antibody responses cautiously.

This Phase III randomized controlled trial compared the immunogenicity and safety of Papilloguard, a quadrivalent HPV vaccine formulated with adjuvant system 04 (AS04), against Gardasil in 670 healthy individuals aged 15-25 years. The primary outcome was immunogenicity, measured by geometric mean concentrations (GMCs) of HPV-specific antibodies at day 210. Papilloguard demonstrated non-inferior immunogenicity compared to Gardasil across all four HPV types. Additionally, geometric mean antibody concentrations were consistently higher with Papilloguard for all four HPV types, and seroconversion rates were higher for HPV types 6, 11, and 18 at day 210. However, these superiority analyses were not prespecified, and the findings should be interpreted cautiously.

Safety data showed that most adverse events were grade 1 or 2. Vaccination site pain was the most commonly reported local solicited adverse event in both groups, while headache and fatigue were the most frequently reported systemic solicited adverse events. Two serious adverse events were reported in each group, none of which were considered related to the vaccines. The overall safety profile of Papilloguard was described as acceptable and comparable to other HPV vaccines, but it was associated with increased local reactogenicity.

Limitations include the non-prespecified nature of the superiority analyses and the lack of reported effect sizes, confidence intervals, and p-values. The follow-up duration was not reported, and the study population was limited to healthy individuals aged 15-25 years, so results may not generalize to other age groups or immunocompromised individuals. The enhanced immunogenicity may be associated with the AS04 adjuvant, but causality is not definitively established.

In practice, Papilloguard appears to be a promising HPV vaccine with enhanced immunogenicity and an acceptable safety profile, though clinicians should be aware of the increased local reactogenicity. The non-inferiority result supports its potential as an alternative to Gardasil, but the lack of long-term efficacy data and the cautious interpretation of superiority findings warrant further research.

How this fits prior evidence

This trial extends prior coverage by demonstrating that a quadrivalent HPV vaccine with AS04 adjuvant is non-inferior to Gardasil in immunogenicity, with higher antibody concentrations and seroconversion rates for some types. It aligns with the prior finding that 3-dose regimens provide high seroconversion, though this study does not report regimen details. It also complements the evidence on HPV vaccination reducing infection, but does not address high-grade lesions. The higher immunogenicity may have implications for populations with high HPV burden, such as men with HIV, but this study did not include such groups.

Researchers conducted a Phase 3 clinical trial involving 670 healthy individuals between the ages of 15 and 25. The study compared the Papilloguard vaccine, which includes an adjuvant system called AS04, against the Gardasil vaccine to see how well they triggered immune responses against four types of human papillomavirus (HPV).

The results showed that Papilloguard was not inferior to Gardasil in creating antibodies at day 210. However, the study also found that Papilloguard produced consistently higher antibody concentrations across all four HPV types compared to Gardasil. Additionally, more people in the Papilloguard group achieved seroconversion for specific HPV types.

Regarding safety, most side effects were mild, such as pain at the injection site, headache, and fatigue. While Papilloguard showed a similar overall safety profile to other vaccines, it was associated with increased local reactions at the site of injection. Because some findings regarding higher antibody levels were not part of the original study plan, these specific results should be viewed with caution. These findings are currently limited to healthy individuals aged 15 to 25.

What this means for you:

Papilloguard shows strong immune responses against HPV and is comparable in safety to other available vaccines.

Common questions

Is the Papilloguard vaccine safe for young adults?

The study found that the safety profile of Papilloguard was acceptable and comparable to other HPV vaccines. Most reported side effects were mild, such as headache, fatigue, or pain at the injection site. While there was more local reaction at the site of injection compared to other groups, no serious adverse events were linked to the vaccine.

How does Papilloguard compare to Gardasil?

The trial showed that Papilloguard was not inferior to Gardasil in creating antibodies at day 210. However, Papilloguard did show consistently higher antibody concentrations across all four HPV types and higher seroconversion rates for types 6, 11, and 18 compared to the Gardasil group.

Who is this vaccine intended for?

The study specifically included healthy individuals between the ages of 15 and 25. Because the trial was limited to this specific age group, the results may not apply to other age groups or people with different health profiles.

Study Details

Study typeRct

Sample sizen = 670

EvidenceLevel 2

PublishedAug 2026

PMID42424856

View Original Abstract ↓

OBJECTIVE: Papilloguard® is developed by Nivad Pharmed Salamat as a quadrivalent human papillomavirus (HPV) vaccine, uniquely combined with the adjuvant system 04 (AS04). The objective of this study was to evaluate the immunogenicity and safety of the quadrivalent Papilloguard® in comparison with Gardasil® (Merck). METHODS: This study enrolled 670 healthy participants aged 15-25 years. Vaccines were administered at Months 0, 2, and 6. Immunogenicity was assessed by geometric mean concentrations of HPV-specific antibodies at days 60, 180, and 210. Safety data were collected through direct monitoring, phone follow-ups, and diary cards. RESULTS: Papilloguard® demonstrated non-inferior immunogenicity compared to Gardasil® across all four HPV types at day 210. Moreover, Papilloguard® demonstrated consistently higher geometric mean antibody concentrations across all four HPV types compared with Gardasil®. Seroconversion rates were also higher for HPV types 6, 11, and 18 at day 210 in the Papilloguard® group. However, superiority analyses were not prespecified and these findings should be interpreted cautiously. This enhanced immunogenicity may be associated with the AS04 in the quadrivalent formulation. Most reported adverse events were grade 1 or 2. Vaccination site pain was observed in both groups as the most commonly reported local solicited adverse event. Headache and fatigue were the most frequently reported systemic solicited adverse events. Two serious adverse events were reported in each group, none of which were considered related to the vaccines. While associated with increased local reactogenicity, the overall safety profile of Papilloguard® was acceptable and comparable to other HPV vaccines. CONCLUSION: Papilloguard®, the first quadrivalent HPV vaccine combined with AS04, demonstrated non-inferior immunogenicity compared to Gardasil® for HPV types 6, 11, 16, and 18. Despite a higher incidence of local reactogenicity, likely associated with AS04, Papilloguard® showed enhanced immunogenicity while maintaining an acceptable overall safety profile, positioning it as a promising HPV vaccine.

Papilloguard with AS04 shows non-inferior immunogenicity to Gardasil in HPV vaccine trialTrial Shows Papilloguard Vaccine Provides Strong Protection Against HPV Infection

How this fits prior evidence

Common questions

Study Details

Intrawound tobramycin plus vancomycin did not reduce deep infection risk compared with vancomycin alone in high-risk tibial fractures

Adding Antibiotics to Bone Surgery Didn't Lower Infection Risk

Clinical research that matters. Delivered to your inbox.

Papilloguard with AS04 shows non-inferior immunogenicity to Gardasil in HPV vaccine trialTrial Shows Papilloguard Vaccine Provides Strong Protection Against HPV Infection

How this fits prior evidence

Common questions

More on Human Papillomavirus Infection

Study Details

Intrawound tobramycin plus vancomycin did not reduce deep infection risk compared with vancomycin alone in high-risk tibial fractures

Adding Antibiotics to Bone Surgery Didn't Lower Infection Risk

Clinical research that matters. Delivered to your inbox.

Related in Infectious Disease

From Other Specialties