Strategies used to improve immunization coverage of nirsevimab in an autonomous community in Spain

ABSTRACT

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract infections, particularly in infants under one year. In 2023, Spain became one of the first countries to implement nirsevimab, a long-acting monoclonal antibody, for RSV prevention. This study evaluates the second immunization campaign in the Region of Murcia, focusing on coverage, timeliness, and equity. A retrospective cross-sectional analysis included children born between April 2024 and March 2025. Coverage was assessed for infants born during and outside the RSV season. Continuous training for healthcare professionals and targeted family education were implemented to improve uptake. Of 12,606 children, 11,785 (93.5%) received nirsevimab, with coverage higher for those born during the campaign (96.0%) than before (90.5%, p < .001). Coverage was higher among children whose health card holder was born in Spain (94.2%) versus abroad (91.9%, p < .001), reducing the previous season’s gap from 5.7% to 2.3%. Most infants (92.4%) were immunized before maternity discharge, with delayed cases receiving protection at a mean age of 22.7 d. High protocol adherence (99.7%) and rapid catch-up immunization were observed. Continuous professional training and public information contributed to improved coverage, timely protection, and reduced inequities, demonstrating the feasibility of nirsevimab implementation in a public health program.

Introduction

Respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in children under five years of age, especially in those under one year.¹ Nevertheless, in high-income countries, the hospital admission rate is highest during the first 6 months of life.² In a multicentre, prospective, observational birth cohort study conducted between 2017 and 2020 in healthy term-born infants at five sites in different European countries (including Spain), the incidence of RSV-associated hospitalizations in the overall cohort was 1.8% (95% CI, 1.6–2.1%) during the first year of life. The majority (57.9%) of RSV-associated hospitalizations occurred in children younger than 3 months, and 84.2% occurred in children younger than 6 months.³

The authorization of nirsevimab – a long-acting monoclonal antibody with high efficacy and a good safety profile – by the European Medicines Agency in 2022, along with the disease burden caused by RSV, led the Spanish National Immunization Technical Advisory Group (NITAG) to recommend its use initially in May 2023⁴ and subsequently for the 2024–2025 season.⁵ The recommendation includes administration to children born between April of one year and March of the next, as well as to those with certain risk conditions, such as prematurity, congenital heart disease, severe lung disease, or immunosuppression, among others. In this way, Spain – along with France, Luxembourg, and the United States – became one of the first countries worldwide to implement this strategy during the 2023–2024 season. Spain is a country with 17 communities and 2 autonomous cities, which are the ones that have been granted authority over healthcare, including immunization programs. Despite the fact that the introduction of vaccination programs and schedules in each of them may have small variations, RSV immunization recommendations have been implemented in a relatively uniform manner across the autonomous communities.

The Region of Murcia, located in the southeast of the country, is an autonomous community with a population of 1,568,492 inhabitants according to the official 2024 census⁶ and 12,860 births in 2023, – representing 4.0% of the national birth cohort.⁷

The first immunization campaign was a success, both in its impact – with an estimated 10,793 RSV-related hospital admissions prevented nationwide among children under one year of age^8,9 – and in regional immunization coverage: 89.67% for the whole target population, 87.73% for those born before the season (from April to September), and 93.08% for new-borns (from October to March).¹⁰ Despite high coverage rates, some evaluated data – such as the delay in immunizing new-borns before discharge from the maternity ward and the lower uptake among children of migrant mothers – indicate room for improvement.

Therefore, the aim of the present paper was to describe the actions and strategies carried out during the second RSV immunization campaign in our autonomous community (2024–2025), as well as to evaluate the results obtained in the target population born from April 2024 to March 2025.

Materials and methods

Evaluation carried out

A retrospective cross-sectional evaluation was carried out on May 6, 2025, of children born between April 1, 2024, and March 31, 2025, who were either immunized or non-immunized with nirsevimab. Demographic characteristics of the children and their health card holders (usually the mother), available in the population database, called PERSAN, were collected. Immunization coverage was calculated separately for two groups: those born out of season and those born during the RSV season. The first group was immunized at their primary health care centers and regular immunization posts as part of a catch-up campaign, while the second group was immunized within the first 48 hours of life before discharge from the maternity hospital or, in cases of refusal, offered immunization at their health centers and regular vaccination posts during subsequent visits.

Activities carried put to improve immunization coverage

Information on the results of the previous campaign for healthcare professionals (HCPs)

Continuing with all the actions developed prior to the 2023–2024 campaign, as previously described by Pérez Martín & Zornoza Moreno (2024),¹¹ the results obtained in this campaign were ultimately communicated to HCPs and nursing and medical directors.

Information, education and awareness campaign for HCPs

Prior to the 2024–2025 campaign, preparatory online meetings were held to inform HCPs about the burden of RSV disease and the impact of nirsevimab using local and national data, as well as to review product characteristics and real-world safety data. They were informed about various evaluated indicators identified during the 2023–2024 campaign, which were established as targets for improvement during the 2024–2025 campaign. These online meetings were held with primary care and hospital HCPs from both the public and private sectors. Despite having emphasized the fundamental role of midwives during the first campaign, in this second campaign (2024–2025), their role in informing families was once again highlighted – not only in prenatal maternal education but also in the active and as early as possible identification of non-immunized new-borns in the maternity ward prior to discharge.

The protocol containing all specifications for HCPs was later shared via e-mail through each center’s vaccination lead and coordinators, and was made available throughout the entire campaign on the official website https://www.murciasalud.es/web/vacunacion/-/virus-respiratorio-sincitial-vrs-1. In addition, starting from the second week of the campaign, immunization coverage data were published on the official website and also shared via e-mail.

Education and awareness campaign for families

For family education and information, brochures were prepared with frequently asked questions about RSV, the benefits of the immunization available in our country, and local real-world safety data.¹² These materials were also translated into Arabic,¹³ the language of the largest immigrant population with language barriers. The Spanish brochures were included in the information folder that families receive with all new-born-related materials before discharge from the maternity ward. Both Spanish and Arabic brochures were available at health centers, regular vaccination posts, and maternity hospitals. In every healthcare setting related to new-borns and toddlers, informational posters with a QR code linking to the official website were displayed, were these frequently asked questions were also available. As in the previous campaign, text messages were sent to mobile phones during the 2024–2025 campaign and also social media and mass media were used to inform families about various important aspects of the immunization. HCPs, more confident due to their previous experience, were provided with lists of their non-immunized patients to actively recruit them through telephone calls.

Evaluation variables and data source

The evaluation variables included: date of birth (age), gender, birth country of the health card holder (usually the mother), date of nirsevimab administration, immunization site, product administered, reason for immunization, and maternity hospital where the baby was born (for those born during the RSV season). All data were obtained from the regional vaccination registry database (VACUSAN) and the population database (PERSAN). Both databases depend on the Prevention and Health Protection Service of the Regional Ministry of Health and are central databases, which include data on both people with public and private health care at the regional level.

Statistical methods

A descriptive analysis was conducted to summarize all demographic and relevant evaluation data.

As data were asymmetric, continuous variables are expressed as medians, and measures of dispersion (range, and interquartile range [IQR]). Categorical variables are described as absolute and relative frequencies. Data analysis was performed both overall and stratified according to the timing of birth in relation to the immunization campaign.

Comparisons between qualitative variables were assessed using the Chi-square test, and differences between quantitative variables were analyzed using U Mann-Whitney test. A significance level of 5% was set. Statistical analyses were carried out using SPSS version 25.

Ethics

We conducted the evaluation in accordance with the Declaration of Helsinki and national legal and ethical data protection requirements. The protocol was reviewed by the Ethics Committee for Clinical Research of Hospital Clínico Virgen de la Arrixaca, the reference center for the Region of Murcia. However, approval and the requirement for informed consent were waived due to the nature of this evaluation as part of a public health program.

Results

Immunization sites

In the Region of Murcia, in the 2024–2025 season, nirsevimab was available for the immunization of healthy new-borns and infants, as well as those with risk conditions, at 157 public health centers and clinics and 6 public maternity hospitals, as well as 13 private vaccination sites and 2 private maternity hospitals.

Doses distribution

A total of 98.43% of the 12,259 distributed doses were reported as administered. Moreover, 99.70% (12,222) of the reported nirsevimab doses were administered to the target population of the 2024–2025 immunization campaign, with only 37 doses given to individuals outside the groups for which nirsevimab was recommended.

Evaluation by population characteristics

The evaluation included 12,606 children born between April 1, 2024, and March 31, 2025, 11,785 of them immunized (representing 93.5% of the total). Immunization coverage was significantly higher among those born during the campaign (96.0%) compared to those born before it began (90.5%) (p < .001). Among the entire target population for whom the nationality of the health card holder was known (12,301), coverage was also higher in children whose card holder was born in Spain (94.2%) than in those whose card holder was born abroad (91.9%) (p < .001). Differences were also observed based on the cardholder’s country of birth, categorized according to WHO Health Regions, as shown in Table 1, along with other sociodemographic data for children immunized both during and prior to the campaign. No statistically significant differences in coverage were found based on the sex of the infants.

Table 1.

Sociodemographic data of children, stratified by immunization status and birth period relative to the campaign.

		Immunized – N (%)	Non immunized – N (%)	p-value
BORN BEFORE THE BEGINNING OF THE CAMPAIGN
Sex	Male	2,862 (89.4%)	339 (10.6%)	.831
	Female	2,671 (89.2%)	322 (10.8%)
Health card holder	Spanish	3,503 (92.0%)	305 (8.0%)	.003
	Migrant	1,804 (89.7%)	208 (10.3%)
WHO Health Regions	Spain	3,503 (92.0%)	305 (8.0%)	<.001
	Western European Region	38 (82.6%)	8 (17.4%)
	Eastern European Region	105 (79.5%)	27 (20.5%)
	African Region	65 (90.3%)	7 (9.7%)
	Eastern Mediterranean Region	874 (88.9%)	109 (11.1%)
	South America Region	672 (92.9%)	51 (7.1%)
	Other regions	50 (89.3%)	6 (10.7%)
All		5,533 (89.3%)	661 (10.7%)
BORN DURING THE CAMPAIGN
Sex	Male	3,258 (92.9%)	250 (7.1%)	.119
	Female	3,104 (92.7%)	244 (7.3%)
Health card holder	Spanish	4,230 (96.2%)	169 (3.8%)	<.001
	Migrant	1,960 (94.1%)	122 (5.9%)
WHO Health Regions	Spain	4,230 (96.2%)	169 (3.8%)	<.001
	Western European Region	62 (88.8%)	7 (10.2%)
	Eastern European Region	115 (90.6%)	12 (94%)
	African Region	77 (97.5%)	2 (2.5%)
	Eastern Mediterranean Region	906 (92.3%)	75 (7.7%)
	South America Region	741 (96.7%)	25 (3.3%)
	Other regions	59 (98.3%)	1 (1.7%)
All		6,362 (92.8%)	494 (7.2%)

Evaluation by timing

When stratified by timing of birth relative to the immunization campaign, infants born during the campaign period and within the RSV circulation season were immunized at ages ranging from 0 to 126 d. The median age at immunization in this cohort was 2.00 d (IQR 1–3) (Figure 1A). Among those who received nirsevimab prior to hospital discharge (92.4% of the whole population), the maximum age at administration was 86 d (in the case of a preterm infant), with a median of 2.00 d (IQR 1–3). There were no significant differences in the age at which children of migrant mothers were immunized in the maternity ward (p = .578), with a median of 2.00 d (IQR 1–3), compared to children of Spanish-born mothers, who had a median of 2.00 d (IQR 1–2). A total of 291 families declined immunization with nirsevimab at the maternity hospital; their children subsequently received the antibody at their primary care center or usual vaccination site, reaching a final coverage of 96.0%. In this subgroup, the median age at immunization was 13.00 d (IQR 4–30). Children of migrant mothers were immunized at a significantly older age than those of Spanish-born mothers, with a median of 17.00 d (IQR 9–63), compared to a median of 14.00 d (IQR 6–21), respectively (p < .001).

Figure 1.

Frequency distribution of immunization. A. Days of life at immunization for children born during the campaign (from September 23, 2024, to March 31, 2025). B. Number of days from the official start of the campaign until immunization for children born before the campaign began (from April 1 to September 22, 2024).

For infants born before the start of the campaign, the key metric was the number of days between the official launch of the campaign and immunization. In this group, the time to immunization ranged from −12 to 191 d, with a median of 11.00 d (IQR 3–25) (Figure 1B). Children of migrant mothers were immunized significantly later than those of Spanish-born mothers, with a median of 17.00 (IQR 7–35) vs. a median of 9.00 (IQR 3–22), respectively (p < .001).

Figure 2 shows the rate of nirsevimab dose administration during the catch-up phase of the campaign, which aimed to immunize the majority of infants born before the onset of the RSV season and viral circulation. During this period, 25% of doses were administered within the first 4 d after the official campaign start date (with some administered up to 12 d earlier), 50% within 14 d, 75% by day 25, and 90% by day 45 (November 7).

Figure 2.

Evolution of the cumulative immunization rate among children born before the start of the campaign (April 1 to September 22, 2024).

Discussion

Spain was one of the first countries in the world to introduce the monoclonal antibody for RSV prevention in infants and to evaluate its effectiveness.¹⁴ The Region of Murcia contributed to the success achieved in Spain, with a coverage rate of 88.3% during the 2023–24 season (91.5% among those born during the campaign and 85.1% among those born before its start).¹¹ In this second season (2024–2025), coverage has improved, rising from 88.3% to 93.5% (96% born during the season vs. 90.5% born before season). The increase in coverage in the years following the implementation of an immunization program has been observed both in our country^15,16 and in countries with very different cultures.¹⁷ This may be due to the greater maturity of the program, increased public awareness, the information provided to health professionals and the general population about the positive impact of the first immunization campaign,^8,9,14,18 as well as the absence of safety alerts following its implementation.

Coverage rates reached 94.2% for children whose parents were born in Spain and 91.9% for those whose health card holders were born abroad. In the previous season, the rates were 91.3% and 85.6%,¹¹ respectively, representing increases of 3% for the Spanish-born population and 6.3% for those of foreign origin. This reduced the coverage gap from 5.7% to 2.3%, increasing the equity of the program and nearly equalizing coverage. Two key actions stand out in this regard: during training sessions for healthcare professionals, the need to reduce this gap was repeatedly emphasized, and materials were translated into Arabic to improve accessibility of the information. Undoubtedly, an important aspect of improvement is evaluating and informing professionals about areas that need enhancement, a practice that has also been described in other European countries.^19,20 Another new feature of this campaign was the translation of materials into Arabic, which may have improved comprehension among the Moroccan-born population, who represent 5.9% of the total population in the Region of Murcia and 38.7% of the foreign population.²¹

92.4% of babies left the maternity ward fully immunized, a figure that increased to 96% through immunization at primary care centers after discharge. This 3.6% difference is lower than the 4.9% observed in the previous campaign,¹¹ indicating a better outcome for this campaign, especially since healthcare professionals were repeatedly informed about the importance of ensuring that the majority of babies leave the hospital immunized. The average age at which babies who left the maternity ward without immunization received the monoclonal antibody also decreased to 22.7 d, compared to 27.4 d in the previous season.¹¹ This is another positive finding, as it reduces the period during which these babies remain unprotected.

Another important piece of data is the immunization pace of the campaign in health centers for children born out of season, as its speed ensures timely protection before the RSV epidemic season begins. In the 2024–2025 season, 25% of doses were administered within the first 4 d, 50% within 14 d, 75% by day 25, and 90% by day 45 (November 7), figures very similar to those of the previous campaign,¹⁰ in which 90% of doses were administered within the first 39 d – still fast enough to ensure protection before the epidemic season.

Both this season and the previous one, the doses have been used in the target population for which they are intended. During the last season, 99.6% of doses,¹¹ and in this season, 99.7%, were administered according to protocol, indicating a high level of rigor on the part of all healthcare professionals involved across 178 health centers and hospitals.

The experience in our region is similar to that observed in Spain; however, it is very different from that described in the US, where by March 2025, 57% of infants under 8 months of age had received protection against RSV.²² This represents an improvement over the 51% of the previous season²³⁰, but it is still far from the coverage rate recorded in Spain. Immunization coverage in France apparently decreased during the second season (76.5% in the first season,²³ and according to the French Society of Pediatrics, only 46% of babies born between February and August 2024 received preventive treatment),²⁴ which is very different from the results we have described.

This study has several limitations that should be considered when interpreting the results. First, it is an observational evaluation based on coverage and process indicators, which precludes establishing direct causal relationships between the implemented interventions and the observed improvements in coverage. In addition, the analysis is limited to a single region, which may restrict the generalizability of the findings to other settings with different sociodemographic, organizational, or cultural characteristics. Moreover, no qualitative information was collected on individual reasons for non-immunization or on families’ perceptions, particularly among populations of foreign origin, which would have allowed for a deeper understanding of the determinants of acceptance.

Key strengths of this study include the high quality and completeness of the data, covering virtually the entire target population and reflecting a high level of protocol adherence across a large number of healthcare centers. The comparative analysis of two consecutive seasons allows for an assessment of the program’s evolution and documents sustained improvements in coverage, equity, and timeliness of immunization. Furthermore, the study highlights specific and reproducible strategies – such as continuous training of healthcare professionals, feedback on results, and culturally adapted informational materials – that are associated with a significant reduction in coverage inequalities. Finally, situating the regional experience within an international context enhances the relevance of the findings and positions the region as a reference for the effective and equitable implementation of RSV prevention programs.

Conclusions

In our region, the RSV prevention strategy using Nirsevimab was successful in its first season of use (2023–24), with coverage rates of 88.3%, rising to 93.5% in the second season. During this second season, a significant decrease in inequality was also observed, with a reduction in the coverage gap between the native and immigrant populations. Continuous training for healthcare professionals and public information campaigns are key to increasing the success of the strategy.

Biography

Jesús Javier Yelo Cano, Specialist Nurse in Family and Community Nursing. Nurse in the Vaccination Program of the Service for Prevention and Protection of Health of the Regional Ministry of Health of the Region of Murcia since 2023. Holder of a Diploma in Nursing from the University of Murcia.

Funding Statement

Article publication charges (APC) were funded by Sanofi Spain.

Disclosure statement

M.Z.M. and J.J.P.M. declare having received funding from AstraZeneca for research, training, and dissemination activities. Additionally, J.J.P.M. discloses the same relationship with Sanofi, and M.Z.M. declares having received funding from Sanofi for research activities. J.J.Y.C. declares no conflict of interest.