Trust Through Candor: Sanofi’s Dr. Mary Bausch-Jurken on MenACYW-TT Safety and Talking About Vaccine Risk

Questions on clinical safety and communication perspective

1. Your review in Expert Review of Vaccines examines the clinical safety evidence for MenACYW-TT. What are the key findings clinicians should take away from the safety data?

Across more than 30 clinical trials and more than 17,000 participants, from infants as young as 6 weeks to older adults, MenACWY-TT (MenQuadfi) showed a consistently favorable and predictable safety profile. Four points matter most to clinicians:

• Reactions are mostly mild and short-lived (generally 1-3 days) and are similar to most vaccines, injection site pain/swelling, mild muscle aches and headache in older age groups, and drowsiness and crying in infants.
• Serious events were rare, reported in fewer than 1% of participants with no deaths reported in the trials.
• Safety was comparable to other quadrivalent conjugate meningococcal vaccines in head to-head studies against MenACWY-CRM, MenACWY-DT and MCV4-TT. Booster doses had a similar profile to the primary dose.
• Coadministration is feasible. MenACYW-TT can be given with routine pediatric and adolescent vaccines without compromising immunogenicity. Higher reaction rates with concomitant dosing appear to come from the coadministered vaccines.

2. How does the safety profile of MenACYW-TT compare across the different age groups studied, including adults and older adults?

The safety profile is broadly consistent across the life course with some expected differences in the type and frequency of reactions, but across all groups vaccine related serious adverse events were rare.

One finding deserves transparent discussion. In one of the infant studies seizures, febrile and non-febrile, were reported in 0.9% of the MenACWY-TT arm. Most occurred outside the 1–2-day window expected for an inactivated vaccine. Two were considered possibly related to the vaccine and followed the fourth dose of PCV13, MMR and varicella vaccines. Neither was prolonged or recurred. Clinicians should be aware of this signal, especially for the 12–18-month age group, while recognizing that the overall benefit-risk profile remains favorable.

3. With vaccine hesitancy and confusion on the rise, how should clinicians communicate about vaccine safety and risk in a way that builds genuine trust?

Trust is built less by reassurance than by candor. Here is what I would encourage clinicians to do.

• Lead with what the patient is likely to experience and describe the common reactions (sore arm, tiredness, headache, muscle aches) and when they typically resolve to set realistic expectations.
• Be upfront about rare events. Hypersensitivity reactions, including anaphylaxis, and convulsions with or without fever have been reported after licensure. Vaccine anaphylaxis is rare, about 1.31 cases per million doses distributed. Febrile seizures occur in 2–5% of children aged 6 months to 5 years, and the risk with MenACYW-TT given alongside routine pediatric vaccines is below 1 case per 1,000 vaccinated. Naming these risks plainly, with numbers, is more credible than omitting them.
• Put risk in context. Rare adverse events should be weighed against invasive meningococcal disease, which can be rapidly life-threatening and life-altering. In the US, 503 cases were reported in 2024, the highest since 2013.
• Explain how we know by describing where the evidence comes from.
• Listen first. Hesitancy may reflect specific concerns or past experiences.

4. What role does transparent reporting of safety evidence play in supporting shared clinical decision-making between clinicians and patients?

Shared decision-making only works when both parties have an accurate picture of benefits, risks, and uncertainties. This is increasingly relevant for meningococcal vaccination. US guidance for adolescent MenACWY vaccination has moved toward shared clinical decision making rather than a routine recommendation, although the American Academy of Pediatrics continues to advocate routine immunization at ages 11–12 with a booster at 16.

Transparent reporting supports this by giving clinicians usable numbers regarding reaction rates and severity and lets clinicians give patients the information. It also makes limitations visible, like lack of data in certain groups (pregnancy, immunocompromised etc.) Acknowledging gaps protects credibility. And lastly, it lets patients weigh what matters most to them. Clear data helps prevent patients going to other, less credible sources, to fill the gaps.

5. Were there any findings in the safety review that you believe are under-appreciated or commonly misunderstood?

• Higher reaction rates with coadministration usually reflect the other vaccines. In MET57, 32.7% of toddlers given MenACYW-TT alone had a solicited injection-site reaction, versus 58.1% with MenACYW-TT plus DTaP-IPV-HepB-Hib and 65.3% with DTaP-IPV HepB-Hib alone. In MET50, 46.6% of adolescents given MenACYW-TT alone reported a local reaction, versus 84.5% with Tdap and HPV added and 82.4% with Tdap and HPV alone. Concomitant administration has not been shown to increase serious adverse events.
• More injection-site reactions in older adults does not mean worse reactions. MenACYW TT caused more local reactions than the plain polysaccharide vaccine in MET49, but severe (grade 3) pain was identical at 0.7% in both arms. This is a known feature of conjugate vaccines.
• Durable protection and booster flexibility. Antibodies were documented up to 7 years after priming. Booster doses enhanced responses regardless of the meningococcal vaccine previously received, including MenACYW-TT, MenACYW-CRM, MPSV4, MenC-TT, and MCV4-TT, and across ages from children to older adults. This matters because individuals’ vaccination histories are often incomplete or mixed.

6. Looking ahead, what further evidence or real-world data would strengthen clinical confidence in meningococcal vaccination strategies?

Real-world effectiveness: Immunogenicity is a standard surrogate endpoint, but it is less intuitive for non-specialists. Data showing reductions in disease incidence, hospitalization, and long-term sequelae would reinforce clinical relevance and public confidence. The issue here is that invasive meningococcal disease is such a rare event, that collecting enough cases to calculate a VE would be very difficult.

Special populations: We need data in pregnant women (the ongoing MEQ00070 registry will help) and in immunocompromised individuals, including people living with HIV, those with asplenia, and those on complement inhibitors. Recent increases in invasive meningococcal disease, driven mainly by serogroup Y, have affected adults aged 30–60, Black and African American populations, and people living with HIV. These groups are specifically recommended for vaccination yet have not been systematically studied with MenACYW-TT.