Need for increasing uptake of influenza vaccination and investing in novel vaccines for paediatric influenza prevention

Despite being offered to all population groups in most high-resource countries, influenza vaccination is especially recommended for high-risk subjects (1,2). Immunocompromised and otherwise comorbid patients are indeed at a higher risk for complications and unfavourable outcomes, and the limited beneficial impact of antiviral therapies against influenza makes it fundamental to provide for preventive measures (3). Moreover, vaccination prevents strain on healthcare systems during epidemic seasons, thus containing medical expenses and favouring a more rational deployment and utilization of healthcare resources (4).

In the article by Hayek et al. (5), a significant vaccine effectiveness (VE) could be identified for both children with and without comorbidities, confirming the value of vaccination in preventing emergency department (ED) access and hospitalization. The data support the beneficial impact for both health children and children with comorbidities to receive influenza vaccination. However, the overall VE was not equally distributed across the study population, with statistically significant effect modification based on the presence of comorbidity [VE in otherwise healthy children: 53%; 95% confidence interval (CI): 47–59%, and VE in children with one or more comorbidities: 43%; 95% CI: 35–50%]. Though comparable, these figures go to show that a gap does exist in terms of vaccination cost-effectiveness between the two groups.

Influenza VE against visit to ED or hospitalization in comorbid patients is difficult to evaluate, as this occurrence could result from the subject’s baseline health conditions in addition to complication of influenza such as pneumonia or encephalopathy. While the observed VE in those with comorbidity needs a careful interpretation, the role of comorbidities in hindering the response to vaccination is well documented. Deregulation and dysfunction of the immune system, as well as interactions with chronically administered therapies, tend to hinder immune response to vaccination. At the same time, specific underlying medical conditions might increase the subject’s vulnerability to influenza and bacterial superinfections thereof (6,7). It is therefore legitimate to hypothesize that the difference observed by Hayek et al. (5) may exist. Nevertheless, the significant protective impact of vaccination against influenza-associated ED visit or hospitalization among both those with and without comorbidity highlights that vaccination is an important tool to mitigate influenza disease burden in children, irrespective of the presence of comorbidity. At the same time, in case of hospitalization, vaccination has been shown to positively impact the outcomes of hospitalization itself, further encouraging this practice (8,9).

It is however relevant to precise that available evidence failed to identify a significant reduction in hospital stay’s length in case of vaccination (8,9). This is especially relevant in the case of young children, who could be significantly distressed by prolonged hospitalization (10,11). Therefore, though limited, the gap observed by Hayek et al. may translate to relevant healthcare expenses, reduced resource availability and, most importantly, psychological suffering for both children and families.

The debate on policies aimed at protecting vulnerable subjects against influenza has been historically focused on the reinforcement of vaccination offer and health literacy. By building confidence and encouraging vaccine uptake, indeed, community immunity could be achieved (12). However, the recent surge of vaccine hesitancy has led to scenarios where high-risk subjects’ needs are not met by the surrounding community, thus highlighting the liabilities in relying on collective responsibility (13). The case of influenza brings forth even more critical points to be addressed, including benefits of repeated annual vaccination and yearly fluctuations of VE due to different circulating strains (14).

However, technological and pharmaceutical advancements have made it possible to introduce new influenza vaccine forms specifically dedicated to high-risk groups. In particular, high-dose influenza vaccines are currently employed for the elderly in order to counteract immunosenescence, while adjuvanted products can be used in highly vulnerable individuals to increase immunogenicity (15). Both these product types have been deployed in adult populations, with evidence of a positive cost-effectiveness profile and no major alerts as far as safety is concerned (16,17).

On the other hand, no dedicated products exist for routine immunization of paediatric patients against influenza. For instance, the live-attenuated nasal spray vaccine also aims at building mucosal immunity to prevent transmission to others. However, the live-attenuated nasal vaccine is generally avoided for immunocompromised populations (18). Novel technologies do have the potential for resulting in innovative platforms for vaccine development and delivery (19,20), but such advancements currently represent a perspective, rather than the state of the art. Novel products based on messenger ribonucleic acid (mRNA) technologies, for example, might be able to increase effectiveness of influenza vaccines by ensuring faster adaptation to circulating strains due to higher malleability of mRNA itself as a molecular platform for immunization products (21). Hayek et al.’s paper (5) remarks the need for dedicated products to be provided to vulnerable paediatric populations, and such innovations could contribute to closing the gap, thus improving quality of life for both comorbid children and their families.

The introduction of new influenza vaccines specifically designed for high-risk paediatric populations, could also improve vaccination uptake in these subjects: apart from improving effectiveness, specific products could help reinforcing the idea of tailor-made resources being deployed for children with risk factors, thus encouraging vaccine uptake. Vaccine hesitancy, indeed, often stems from lack of perceived utility of the vaccine itself (22), and the availability of a dedicated vaccine could positively change this belief in guardians (23). Moreover, an increase in investments dedicated to research and development of new products for paediatric use could help improve the general public’s trust towards research in general, in a moment of historically low trust in the pharmaceutical corporate world (24).

All things considered, increasing vaccination coverage remains the top priority for all healthcare professionals, and is especially crucial as far as highly vulnerable individuals are concerned. Tailored multidisciplinary interventions are required, including education of caregivers, dissemination of evidence related to vaccine safety, and activation of dedicated outpatient services for both routine and extraordinary immunization of children with specific health needs (23,25). In particular, limited accessibility of paediatric vaccination services may represent a major barrier to vaccination. Several experiences have demonstrated that school-based immunization campaigns (26), enhanced involvement of pharmacists and local medical clinics (27,28) are valuable strategies for improving accessibility and equity in vaccination offer. Finally, the role of community immunity should be emphasized in the public health context, pressing for shared responsibility in shielding those who might either not be eligible or fail to respond to vaccination.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article has undergone external peer review.

Peer Review File: Available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0346/prf

Funding: None.

Conflicts of Interest: Both authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0346/coif). T.K. has received grants from BioMérieux. The other author has no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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