Taxonomy of the Full Health and Societal Value of Maternal Vaccination to Prevent Infant Respiratory Syncytial Virus Disease

Abstract

We provide a taxonomy of the full health and societal value of maternal vaccination (MV) to prevent infant respiratory syncytial virus (RSV) disease. RSV is the leading cause of acute lower respiratory tract infections in infants and young children. Most children are infected by RSV before age one, and by age two, infection is nearly universal. Most cases are mild, but some are severe and can result in hospitalization, death, or long-term complications. RSV disease burdens have global scope but are typically higher in low- and middle-income countries. Globally, most severe cases occur among term and previously healthy infants, making RSV prevention in all infants a public health priority. Preventing infant RSV requires reliance on passive rather than active immunity. One recently developed passive immunization is RSVpreF, which has been found to be efficacious and to have an overall favorable safety profile, and which national immunization authorities will soon consider for inclusion in immunization schedules. Essential to realizing MV’s potential contribution to this global public health priority are optimal coverage decisions by vaccine payers, informed by accurate value-for-money (VfM) assessments. To support VfM assessments and optimal coverage decisions, we formulate a taxonomy of the values promoted by MV. This taxonomy distinguishes between narrow health benefits and broader socioeconomic benefits. It distinguishes among benefits to infants; the mother, parents, caregivers, and household members; the health system; and the broader population, society, and government. Value elements include infant health (including from reduced mortality, severe disease, and long-term complications), reduced health system costs, reduced caregiver burdens, financial risk protection, parental peace of mind, averted parental bereavement, process utility from transference of injection burdens and risks from infant to mother, health and socioeconomic equity, antimicrobial resistance reduction from averted inappropriate antibiotic use, potential enhanced education from reduced long-term sequelae, and potential herd effects.

Key Summary Points

Respiratory syncytial virus (RSV) prevention among all infants is a global health priority.

Passive immunization products for infant RSV have recently become available, and country health payers around the globe will soon be making decisions regarding their coverage in immunization schedules.

One immunization strategy for the prevention of infant RSV is maternal vaccination (MV), and optimal coverage decisions for MV must be informed by its full health and societal value.

To inform national MV coverage decisions, we constructed a comprehensive taxonomy of its full health and societal value, which spans both its narrow health-related impacts and its broader socioeconomic impacts.

Our taxonomy both enumerates and imposes conceptual structure on the elements of such full value. Value elements include infant health (including from reduced mortality, severe disease, and long-term complications), reduced health system costs, reduced caregiver burdens, financial risk protection, parental peace of mind, averted parental bereavement, process utility from transference of injection burdens and risks from infant to mother, health and socioeconomic equity, antimicrobial resistance reduction from averted inappropriate antibiotic use, potential enhanced education from reduced long-term sequelae, and potential herd effects. Some value elements specific to MV and not represented in prior taxonomies include averted bereavement from infant mortality and the spillover effects of improved antenatal care systems. Some taxonomy elements are supported by suggestive but not definitive causal evidence and require further investigation, such as long-term sequelae and their educational and productivity consequences, and herd effects.

Introduction

Infant RSV Disease Burden

Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory tract infections (LRTIs), including bronchiolitis and pneumonia, in infants and young children [1]. In 2019, an estimated 33 million global cases of RSV-associated LRTIs occurred in children under five, resulting in about 3.6 million hospitalizations [1]. Globally, most children are infected with RSV in their first year of life (e.g., 53.4% in the United States (US) [2]), and by age two, infection is nearly universal [3, 4].

About 90% of cases are mild [5], manifesting as cold-like symptoms. However, infections can be severe in infants < 3 months and in young children with risk factors, such as prematurity or congenital heart disease [6–8]. Severe infections can result in mortality and short- and long-term health risks and complications, summarized in Table 1. Some of these complications are causally well established, such as otitis media [9] and decreased lung function [9, 10]. Others remain under investigation, with suggestive but inconclusive causal evidence, such as recurrent wheezing and asthma [11]. Some are common, such as otitis media, and others are rare, such as those associated with vertical transmission and the resulting adverse birth outcomes [12, 13].

Table 1.

Infant respiratory syncytial virus (RSV)-related health risks

Mild upper respiratory tract infections

Rhinorrhea; nasal congestion; cough; sneezing; fever; myalgia—Jain et al. (2024) [162]

Croup—WHO (2025) [45]

Severe acute lower respiratory tract infections (LRTIs)

Bronchiolitis—Jain et al. (2024) [162]

Pneumoniaa—Jain et al. (2024) [162]

Complications associated with severe LRTIs

Otitis media—Zar et al. (2024) [9]

Seizures—Saravanos et al. (2021) [163]; Eisenhut (2006) [164]; Stravoravdi et al. (2025) [142]

Apneaa—Jain et al. (2024) [162]; Robinson and Busl (2020) [165]; Stravoravdi et al. (2025) [142]

Myocarditis—Eisenhut (2006) [164]

Tachycardia—Eisenhut (2006) [164]

Endocrine system effects—Eisenhut (2006) [164]

Liver complications—Eisenhut (2006) [164]

Nosocomial infections—Kidszun et al. (2013) [166]

Sepsis—Kidszun et al. (2013) [166]

Respiratory failurea—Jain et al. (2024) [162]

Acute respiratory distress syndrome—Nye et al. (2016) [167]

Deatha—Jain et al. (2024) [162]; Eisenhut (2006) [164]

Long-term sequelae associated with infant RSV

Recurrent wheezingb—Zar et al. (2024) [9]; Fauroux et al. (2017) [10]

Asthmab—Zar et al. (2024) [9]; Fauroux et al. (2017) [10]; Rosas-Salazar et al. (2023) [11]

Decreased lung function—Zar et al. (2024) [9]; Fauroux et al. (2017) [10]

Allergiesb—Fauroux et al. (2017) [10]

Recurrent LRTI—Zar et al. (2024) [9]

RSV-related secondary infections

Viral infections

Influenza A and B—Haney et al. (2022) [168]

Rhinovirus—Halabi et al. (2022) [169]

Human metapneumovirus—Halabi et al. (2022) [169]

Adenovirus—Halabi et al. (2022) [169]

Parainfluenza—Halabi et al. (2022) [169]

SARS-CoV-2—Halabi et al. (2022) [169]

Bacterial infections

Haemophilus influenzae type B—Hishiki et al. (2011) [170]; Wiegers et al. (2019) [171]

Streptococcus pneumoniae—Hishiki et al. (2011) [170]; Wiegers et al. (2019) [171]

Staphylococcus aureus—Wiegers et al. (2019) [171]

Moraxella catarrhalis—Wiegers et al. (2019) [171]

Risk of interaction with comorbidities

Preterm delivery—Resch et al. (2012) [172]

Chronic lung disease—Resch et al. (2012) [172]

Congenital heart disease—Resch et al. (2012) [172]

Neuromuscular disorders—Resch et al. (2012) [172]

Immunodeficiencies—Resch et al. (2012) [172]

Cystic fibrosis—Resch et al. (2012) [172]

Down syndrome—Lowensteyn et al. (2020) [107]

Vertical transmission of RSV infection during pregnancya—Manti et al. (2022) [12]

Adverse pregnancy outcomes related to vertical transmission of RSV infection: during pregnancy

Preterm birth—Manti et al. (2022) [12]; Andrade et al. (2022) [13]

Low birth weight—Manti et al. (2022) [12]

Selective immune deficiency—Manti et al. (2022) [12]

Childhood chronic airway dysfunction—Manti et al. (2022) [12]

Long-term and potentially lifelong neurocognitive and behavioral impairment—Andrade et al. (2022) [13]

LRTI lower respiratory tract infection

^aHealth outcomes that are rare

^bAssociation is well established but causation remains unproven

RSV infections follow distinct seasonal patterns, peaking in the winters of the temperate northern and southern hemispheres; and during the rainy season, though with more variability, in equatorial, tropical, and high-humidity regions [14].

The first few months of life are the age of highest RSV infection risk, especially during the RSV season, and the age of highest severe infection risk [15, 16]. In the US, for example, over half of infant hospitalizations occur within the first 3 months of life, and over three-fourths occur within the first 6 months [17]. Globally, there were 1.4 million hospitalizations and 13,300 in-hospital deaths for RSV LRTI in infants under 6 months in 2019 [18].

The burden of RSV is disproportionately borne by low- and middle-income countries (LMICs): 95% of RSV-related episodes and more than 97% of RSV-related mortality in children under five occurs in LMICs [1, 5]. Approximately half of these deaths worldwide occur in infants younger than 6 months of age [19]. Globally, the majority of severe cases occur among term and previously healthy infants [6, 7, 20], making prevention for all infants a public health priority.

Infant RSV Disease Treatment, Prevention, and Transmission

Treatment

The only approved RSV treatment is ribavirin [21]. However, its use is limited to life-threatening infections because of its toxicity, inconvenient administration route, risks to healthcare worker safety, and limited efficacy [21]. Because many severe RSV cases occur in the first 3 months after birth in otherwise healthy infants [4, 22], and given limited treatment options, prompt and effective RSV prevention in all newborns is essential.

Prevention

The development of RSV prevention in newborns via active immunization, which depends on the vaccine recipient’s own immune system to generate antibodies, has encountered significant challenges, and is therefore not available. These challenges include the immaturity of the infant immune system [23, 24] and safety [23–25]. Passive immunization, whereby antibodies are produced externally and delivered to the infant, is therefore more promising [26].

There are two modes of passive immunization available for the prevention of RSV disease among infants. One prevention strategy is maternal vaccination, in which the infant receives maternal antibodies trans-placentally in utero. The second is direct administration of monoclonal antibodies (mAb) to the infant at birth or soon after.

In 1998, the US Food and Drug Administration (FDA) approved the mAb palivizumab for preventing RSV in children at risk of severe infection [27]. However, that restrictive indication along with its high cost and demanding monthly dosing schedule make it unsuitable for preventing RSV disease in all infants globally [28].

Nirsevimab (Beyfortus, Sanofi, and AstraZeneca) is a single-dose long-acting recombinant mAb with an extended half-life that is administered at birth (or soon after) to infants who are born during the RSV season, or to older infants just before entering their first RSV season. A single dose of nirsevimab is shown to protect against medically attended and severe RSV LRTI through 150 days post-injection [29, 30], the duration of the typical RSV season [19, 31]. Nirsevimab was first licensed for such use in 2022 in the European Union (EU) [32] and United Kingdom (UK) [33], and was licensed for use in the U.S. in 2023 [29]. In 2025, the FDA and European Medicines Agency approved a new mAb, clesrovimab (Enflonsia, Merck) [34, 35]. Clesrovimab is a single-dose long-acting mAb administered at or soon after birth that is shown to protect infants from medically attended RSV LRTI and RSV-associated disease through 150 days post-injection [36, 37]. Clesrovimab is currently being considered for recommendation by the US Centers for Disease Control and Prevention (CDC) [38], and is likely to be considered by licensing authorities and immunization recommending bodies globally in the near future [39].

RSVpreF (Abrysvo, Pfizer) is a single-dose bivalent stabilized RSV prefusion F protein maternal vaccine without adjuvant that is administered within antenatal care (ANC) beginning in the third trimester of pregnancy through 36 weeks of gestation [40]. It is shown to protect infants against medically attended hospitalized RSV LRTI through 180 days post-injection [41]. RSVpreF was first licensed for such use in 2023 in the US [42] and EU [33]. (We henceforth use “MV” to denote maternal vaccination for infant RSV disease prevention, whether with RSVpreF or some other vaccine.)

Adverse Events and Safety

Adverse event risks of MV may include preterm birth (PTB). The RSVPreF3-Mat trial was halted because of higher relative risk of PTB (statistically significant) and neonatal deaths (non-statistically significant) in the vaccinated group relative to placebo [43]. The pivotal RSVpreF trial found a non-statistically significant imbalance in PTB in the vaccinated group relative to the placebo group [41, 44]. The FDA holds that “data are insufficient to establish or exclude a causal relationship” between RSVPreF and PTB, but restricted the RSVPreF indication to 32 through 36 weeks of gestational age to avoid this risk [44]. Post hoc analysis showed that the PTB imbalance occurred in South Africa, a non-high-income country [45, 46]. Subsequent observational studies have failed to establish a statistically significant causal effect of RSVPreF on PTB [47–51].

Adverse event risks of MV may also include hypertensive disorders of pregnancy (HDP). The RSVPreF3-Mat found a non-statistically significant association between vaccination and HDP [43], while the RSVPreF trial found a statistically significant association [41]. Another observational study found a statistically significant association of RSVPreF with HDP meriting further study [47], though two found no such association [49, 50]. Post-licensure market surveillance of RSVPreF, including monitoring adverse events, is ongoing [52].

Infection, Transmission, and Herd Effects

The pivotal RSVPreF trial did not assess prevention of infection or transmission [41], and its real-world use is too recent to detect population-level transmission impacts. Therefore, there is no direct evidence for or against its impacts on infection, transmission, or herd effects. However, enough indirect evidence suggests the possibility of such prevention and consequent herd effects to merit further study and consideration. In an adult challenge trial, RSVPreF was shown effective against symptomatic RSV infection and viral shedding [53]. In addition, an antiviral candidate targeting the same RSV F protein-mediated fusion mechanism as RSVPreF was shown to reduce the duration and level of shedding [54–56]. Vectored RSV vaccine candidates were also found to protect against RSV infection in calves, rodents, and non-human primates [57, 58]. Such impacts have been sufficiently suggestive of MV effectiveness against infant human infection and transmission that modeling studies have assumed such protection [54, 59, 60] and shown it to result in herd protection benefits [54]. Future MVs may also yield such benefits. Such hypothesized protection should be assessed in future work for both RSVPreF and other potential MVs. In what follows, we signal the possibility but lack of direct evidence for these effects by referring to “potential household herd effects” and “potential population herd effects”.

Recommendations

The World Health Organization (WHO) recommends that all countries introduce products for preventing RSV in all infants and leaves individual countries to choose between RSVpreF and a long-acting mAb according to factors such as cost-effectiveness, implementation feasibility, costs, expected coverage, supply, and financing [45]. National immunization authorities such as the US CDC [15] and UK Joint Committee on Vaccination and Immunisation [33] also recommend that all infants be protected against RSV disease with either nirsevimab or RSVpreF.

Value Taxonomy to Support Value-for-Money Assessment of a Maternal RSV Vaccine

Given the public health priority of infant RSV disease prevention and given findings of RSVpreF efficacy and overall favorable safety profile, national immunization authorities worldwide are, or will soon be, making decisions regarding MV inclusion into their immunization schedules. To guide such decision-making, most countries have a National Immunization Technical Advisory Group that conducts health technology assessments (HTA) of immunizations under consideration. HTAs typically consider evidence on disease burden, safety and efficacy, implementation feasibility, economic evaluations (including value-for-money (VfM) and budget impact), and ethical and legal considerations [61, 62]. The vaccine payer, typically a health ministry or department, uses HTA findings to inform coverage decisions.

Limited resources and unlimited needs, both within health sectors and societies in general, make VfM a critical determinant of funding and coverage decisions. (VfM assessments are often called “cost-effectiveness analyses” or CEAs, but strictly speaking, CEAs are just one type of VfM assessment, so we use the more general term.) For example, the WHO Strategic Advisory Group of Experts on Immunization recommends “cost-effectiveness and cost-utility [analyses] of RSV immunization products” [63]. Similarly, the RSV Maternal Immunization Roadmap [64] recommends assessing the return on investment to a maternal RSV vaccine to support financing decisions.

Value taxonomies attempt to enumerate and impose conceptual structure on the types of value that can, or ought to be, considered in VfM assessments and coverage decisions. Taxonomies support VfM assessments by identifying, highlighting, or theoretically developing value elements in ways that support their subsequent quantification. They also support VfM assessments by calling attention to currently unquantified elements, so that decision-makers can consider them qualitatively. Such taxonomies thereby support better reimbursement and recommendation decisions and optimal vaccine spending. They also help summarize existing research and inform future research.

To facilitate such VfM assessments of MV, we construct a comprehensive taxonomy of its health, economic, and social values. This taxonomy applies to RSVpreF and other future MVs. We adopt a broad global perspective and include value elements relevant to both developed and developing countries.

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.

The Broad Value Perspective

Perhaps the most important policy question in value assessment of vaccinations is whether to value technologies narrowly or broadly. Narrow valuation focuses on health-centered outcomes, for example, health impacts and health system costs. Broad valuation expands the scope to include impacts on the broader economy and society (e.g., productivity).

Broad valuation is essential to achieving optimal allocations of constrained national health payer budgets and optimal decisions regarding the scale of those budgets. Omitting vaccinations’ broader values omits a potentially quantitatively significant class of benefits. This risks vaccine undervaluation, which can lead to sub-optimal exclusions from vaccine schedules and underinvestment by health payers in valuable vaccines. Sub-optimal vaccine coverage and underinvestment result in foregone health and socioeconomic benefits, creating risks to population health and income. Given the disproportionate burden of infant RSV in LMICs and vulnerable populations within countries, such underinvestment has inequitable consequences, both globally and nationally. Underinvestment also sends adverse market signals that disincentivize future research and development (R&D). Reduced R&D in turn deprives us of the health, socioeconomic, and equity benefits of foregone future vaccines. In sum, omitting broad values conduces to lower health and income and greater health and socioeconomic inequities, both nationally and globally, both now and in the future.

Taxonomy of the Full Health and Societal Value of Maternal Vaccination to Prevent Infant RSV Disease

We structure the taxonomy by distinguishing between narrow and broad values, and among beneficiaries. Narrow values are health-related values, while broad values are non-health-related values, including socioeconomic values. Among beneficiaries, we distinguish among infants; mothers, parents, caregivers, and household members; the health system; and the population, society, and government.

The taxonomy is shown in Table 2. Column 1 lists the value element, characterizing whether it is health-related (i.e., narrow) or broad and describing its beneficiary. Columns 2 through 7 indicate whether that value element is found in selected value frameworks (Beck et al., 2022 [65]; Bell et al., 2022 [66]; Gavi Vaccine Investment Strategy (VIS), 2024 [67]; Hutubessy et al. (2023) (WHO Full Value of Vaccine Assessment (FVVA)) [68]; Sevilla, 2022 [69]; and Shafrin et al., 2024 [70]). We selected these value frameworks for comparison because they are either highly relevant to a comprehensive valuation of MV and/or are increasingly relied upon by policymakers worldwide. Column 8 describes methods typically used to quantify the value element and examples, if available, of papers quantifying those value elements.

Table 2.

Taxonomy of the full value of maternal RSV vaccination (MV)

Value element	Beck et al. (2022) [65]	Bell et al. (2022) [66]	Gavi VIS (2024) [67]	Hutubessy et al. (2023) [68]	Sevilla (2022) [69]	Shafrin et al. (2024) [70]	Methods and measures
(1)	(2)	(3)	(4)	(5)	(6)	(7)	(8)
1. Health-related benefits to infants
1.1. Reductions in mortality and morbidity	✓	✓	✓	✓	✓	✓	Value elements 1.1, 1.2, and 1.3 are typically measured in QALYs or DALYs. Estimates for MV include Do et al. (2023) [96]; Gebretekle et al. (2024) [159]; Guinazu et al. (2024) [160]; Hodgson et al. (2024) [81]; and Shoukat et al. (2023) [161]
1.2. Reductions in mortality and morbidity from vertical transmission (see Table 1)	✓	✓	✓	✓	✓	✓
1.3. Offsetting adverse effects of maternal RSV vaccination (MV)			✓	✓	✓	✓
1.4. Health risk protection	✓	✓	✓	✓	✓	✓	The value of health risk protection can be valued at WTP for reduction in variance in QALY or DALY outcomes (Lakdawalla and Phelps, 2022 [173]; Shafrin et al., 2024) [70]
1.5. Non-specific effects	✓				✓	✓	Non-specific effects are health impacts (both beneficial and adverse) beyond the targeted infection. Can be measured through QALYs or DALYs. (Aaby et al., 2014 [72])
1.6. Adherence-improving factors					✓	✓	The value of vaccine characteristics that raise uptake and adherence to clinical guidelines regarding the optimal use of the technology. Can be measured through QALYs or DALYs resulting from improved adherence
2. Health-related benefits to mothers, parents, caregivers, and household members
2.1. Reduced maternal infections
2.1.1. Health gains	✓	✓	✓	✓	✓	✓	Value elements 2.1.1 and 2.1.2 are typically measured in QALYs or DALYs. Estimates for MV can be found in Hodgson et al. (2024) [81]
2.1.2. Offsetting adverse effects			✓	✓	✓	✓
2.2. Other household health-related effects
2.2.1. Peace of mind		✓			✓	✓	Value element 2.2.1 is the peace of mind parents gain from reduced risk of infant disease. Can be measured through QALYs, DALYs, or WTP (Lakdawalla et al., 2018 [74])
2.2.2. Averted mental and physical health burdens of caregiving	✓				✓	✓	Measured in QALYs or DALYs
2.2.3. Averted bereavement from infant mortality							Measured in QALYs or DALYs
2.2.4. Household herd effects	✓	✓	✓		✓		Measured in QALYs or DALYs
2.2.5. Process utility					✓		An example of process utility in the context of MV is the psychological benefit to parents from shifting risk and discomfort of injections from infant to mother. Can be evaluated using WTP (Aviles-Blanco, 2021 [174])
2.2.6. Health risk protection		✓	✓	✓	✓	✓	The value of health risk protection can be valued at WTP for reduction in variance in QALY or DALY outcomes (Lakdawalla and Phelps, 2022 [173]; Shafrin et al., 2024 [70])
3. Health-related benefits to health systems
3.1. Health system costs							Typically measured as opportunity cost of health sector resources consumed (Neumann et al., 2017 [148])
3.1.1. Averted treatment costs	✓	✓	✓	✓	✓	✓	Costs of treating RSV disease averted by MV. Empirical estimates can be found in Do et al. (2023) [96]; Gebretekle et al. (2024) [159]; Guinazu et al. (2024) [160]; Hodgson et al. (2024) [81]; and Shoukat et al. (2023) [161]
3.1.2. MV program costs	✓	✓	✓	✓	✓	✓	Costs of MV programs, including costs of vaccine doses, labor, storage, transport, and capital investments. Empirical estimates can be found in Do et al. (2023) [96]; Gebretekle et al. (2024) [159]; Guinazu et al. (2024) [160]; Hodgson et al. (2024) [81]; and Shoukat et al. (2023) [161]
3.1.3. Reduced public health costs	✓	✓	✓	✓	✓		Cost offset to health system measured by reductions in RSV-related patient management expenditures within the health system (e.g., gowns, masks, and gloves) (Bont, 2009 [175])
3.2. Health system strengthening
3.2.1. Reduced congestion and crowding from RSV outbreaks	✓				✓		Existing measures of congestion and overcrowding in the respiratory virus context include wait times, length of stay, emergency room revisits, and overcrowding scores (Janke et al., 2023 [176]; Van Der Linden et al., 2023 [177]). Methodological innovation is needed to integrate these measures into existing VfM measures such as ICERs or net monetary benefits. Can be considered qualitatively or through multiple criteria decision analysis (Thokala et al., 2016 [178])
3.2.2. Improved antenatal care (ANC) systems							Methodological innovation is needed to measure this value element and integrate such measures into existing VfM measures such as ICERs or net monetary benefits. A possible indicator is projected cost savings realized within non-MV programs enabled by MV-related investments in ANC infrastructure
4. Health-related benefits to the broader population
4.1. Public health benefits
4.1.1. Herd effects	✓	✓	✓	✓	✓		Measured in QALYs or DALYs gained and treatment costs averted among non-immunized individuals
4.1.2. Disease control	✓		✓	✓	✓		Percent reduction in infant RSV-related hospitalizations and NICU admissions (Hogan et al., 2017 [60])
4.1.3. Reductions in antimicrobial resistance (AMR)	✓	✓	✓	✓	✓		Methodological innovation is needed to measure this value element and integrate such measures into existing VfM measures such as ICERs or net monetary benefits. In principle, AMR reduction value can be quantified in terms of resistant-disease-related QALYs or DALYs and health system costs impacts, which can be integrated into standard VfM measures (Sevilla et al., 2018 [69]). In practice, a proxy measure of AMR-related indirect effects from MV is the number of antimicrobial prescriptions averted, which can be valued at an estimate of the economic cost per unit antimicrobial consumed (Shrestha et al., 2018 [179])
4.2. Health equity benefits	✓	✓	✓	✓	✓	✓	Can be defined as the value of improving the distribution of health gains across patient sub-groups. Can be operationalized by weighing health gains of the less healthy or more disadvantaged groups by more than the corresponding gains of other groups (Shafrin et al., 2024 [70])
5. Broad benefits to infants
5.1. Education	✓	✓		✓	✓	✓	Measured by change in lifetime earnings resulting from improved cognition and educational attainment due to avoided disease (White et al., 2024 [180]; WHO, 2019 [181])
5.2. Productivity
5.2.1. Paid work	✓	✓	✓	✓	✓	✓	Typically measured as the product of expected number of work hours lost, % of normal productivity lost during those work hours (e.g., 100% for absenteeism, and < 100% for presenteeism), and total compensation per hour of normal productivity (Neumann et al., 2017 [148]; Lakdawalla et al., 2018 [74])
5.2.2. Unpaid work	✓		✓		✓	✓	Typically measured as the product of expected unpaid work hours lost (e.g., time spent on housework, caregiving, and volunteering) and hourly wage plus fringe benefits (Neumann et al., 2017 [148]; Lakdawalla et al., 2018 [74])
5.3. Income	✓	✓	✓	✓	✓	✓	Total financial costs incurred by the household in seeking or receiving care for the infected infant. Includes OOP costs for formal and informal health care. Examples of empirical estimates of averted OOP costs from MV are in Gebretekle et al. (2024) [159] and Shoukat et al. (2023) [161]
5.4. Financial risk protection	✓	✓		✓	✓	✓	The value of financial risk protection is typically measured as WTP for reduction in the variance of financial costs associated with a disease (Lakdawalla and Phelps, 2022 [173]; Shafrin et al., 2024 [70]). A central element of financial risks is uncertainty over OOP costs for formal healthcare
5.5. Consumption					✓	✓	Averted consumption losses from infant disease (Murphy and Topel, 2006 [147]; Neumann et al., 2017 [148])
5.6. Leisure	✓				✓		Typically measured as the product of averted losses in leisure hours and hourly wage plus fringe benefits (Murphy and Topel, 2006 [147]; Neumann et al., 2017 [148])
6. Broad benefits to mothers, parents, caregivers, and household members
6.1. Education	✓	✓		✓	✓	✓	Same as 5.1
6.2. Productivity							Same as 5.2
6.2.1. Paid work	✓	✓	✓	✓	✓	✓	Same as 5.2.1
6.2.2. Unpaid work	✓		✓		✓	✓	Same as 5.2.2
6.3. Income	✓	✓	✓	✓	✓	✓	Same as 5.3
6.4. Financial risk protection	✓	✓		✓	✓	✓	Same as 5.4
6.5. Consumption					✓	✓	Same as 5.5
6.6. Leisure	✓				✓		Same as 5.6
7. Broad benefits to the broader population, society and governments
7.1. Fiscal effects		✓		✓	✓		Change in tax revenue and transfer payments attributable to changes in mortality and morbidity caused by the vaccine (Hutubessy et al., 2023 [68]; Suh et al., 2022 [127]). Can be measured using a fiscal health modelling framework (Connolly and Kotsopoulos, 2020 [158])
7.2. Socioeconomic equity	✓	✓	✓	✓	✓	✓	Can be defined as the value of improving the distribution of well-being in the population. Can be operationalized by wellbeing gains of the worse off by more than the corresponding gains of the better off groups. (Adler, 2019 [182])

AMR antimicrobial resistance, ANC antenatal care, DALY disability-adjusted life-year, ICER incremental cost-effectiveness ratio, MV maternal RSV vaccination, NICU neonatal intensive care units, OOP out-of-pocket, QALY quality-adjusted life-year, RSV respiratory syncytial virus, VfM value-for-money, VIS Vaccine Investment Strategy, WHO World Health Organization, WTP willingness-to-pay

In what follows, we use “health” to encompass mortality and morbidity reductions, physical and mental health, and short- and long-term (including lifetime) outcomes. When we refer to narrow and broad benefits associated with the infant, we mean those associated with the infant’s disease. When we refer to narrow and broad benefits associated with mothers, parents, caregivers, and household members, we mean those associated with their own health, their caregiving, and their relationship with the infant. We provide each value category with a parenthetical reference to the value index in column 1 (e.g., (3.1.1) for “averted treatment costs”).

Health-Related Benefits to Infants

The central value elements in the taxonomy are health gains to the immunized infant. These include averted mortality and morbidity from mild and severe disease, acute- and long-term disease, complications, coinfections, and sequelae (1.1) [71]. These gains may also come from averted vertical transmission of RSV (1.2), which, though rare, can result in spontaneous abortion, fetal death, and other adverse birth outcomes [12, 13], and from averted post-partum transmission from mother to infant [64]. Health risk protection (1.4) involves the value to the risk-averse of MV-induced reductions in uncertainty or variance of future health [70]. (Although it is parents who are likely risk averse, we place this value element in this section since it is uncertainty in infant health that drives this value, and parents’ risk aversion reflects their concern for the infant’s interests.) MV may also induce non-specific or heterologous effects, that is, protection from non-target pathogens (1.5). Such effects are documented for many vaccines [72] but remain under investigation for RSV [73].

Offsetting these health gains are adverse effects risks (1.3) described in “Infant RSV Disease Treatment, Prevention and Transmission”. Adherence-improving factors (1.6) are MV attributes that may raise uptake and adherence to clinical guidelines regarding its optimal use [74]. Such factors may include simplicity, convenience, and acceptability. Surveys show parental acceptability of MV and RSVPreF, which can support adherence [75–78]. However, RSVPreF requires an ANC visit during a narrow gestational age window, which may hinder adherence, especially where ANC accessibility is an issue or when timing is inconvenient.

Health-Related Benefits to Mothers, Parents, Caregivers, and Household Members

RSV has been considered a potentially important but underappreciated pathogen during pregnancy [79, 80]. MV may provide immunity during pregnancy (2.1), though this is unconfirmed for RSVPreF and should be investigated for future MVs [81]. Offsetting these potential maternal health gains are adverse effect risks (2.1.2) described in “Infant RSV Disease Treatment, Prevention and Transmission”. Mothers, parents, caregivers, and household members may also experience health benefits from peace of mind (i.e., reduced worry about infant disease risk) (2.2.1) [82], averted mental and physical health burdens of caregiving (2.2.2) [83–85], averted bereavement from infant death (2.2.3) [86–89], potential household herd effects (2.2.4) discussed below, and the associated reductions in uncertainty regarding the health of these other household members (2.2.6).

Values to parents include process utilities (2.2.5), which are aspects of the process of receiving MV that are valuable independently of their health impacts, such as reductions in inconvenience, discomfort, embarrassment, and invasiveness. One possible MV-related example is the potential psychological benefits of shifting the risk and discomfort of injections from the infant to the mother [75, 77, 78, 90, 91].

The possible but unconfirmed prevention of infection and transmission discussed in “Infant RSV Disease Treatment, Prevention and Transmission” suggests potential household herd effects (2.2.4), though this requires further investigation. Kenyan evidence suggests infant RSV infection is acquired from outside the household in 32% of cases, from older siblings in 39% of cases, and from other household members in 15% of cases [92]. Duration of shedding is highest in infants and decreases with age [93]. These findings suggest that if MV prevention of infant infection and transmission can be confirmed, potential household herd effects could follow. Potential infant immunity may therefore potentially shield non-infant household members from outside infections and from infections of other household members.

Health-Related Benefits to Health Systems

Health system impacts include averted direct costs of treating RSV disease (3.1.1) [94–97], the costs of MV itself (3.1.2), reduced costs of public health response to RSV outbreaks (3.1.3), and various health system strengthening benefits (3.2). Direct costs are costs of formal healthcare, which are averted through the direct effects and potential herd effects of MV in preventing disease. They include costs associated with mild- and severe-, acute- and post-acute-, and non-complicated and complicated disease.

MV program costs include costs of vaccine doses, labor, storage, transport, and capital investments. ANC systems are underdeveloped in many LMICs [98, 99] and some high-income countries [100–102], which constrains MV provision and uptake. Scaled-up MV provision and uptake may therefore incur program costs in terms of necessary ANC-strengthening investments (3.2.2) [64, 103]. Public health response costs include those associated with outbreak surveillance and monitoring (e.g., the US CDC’s RSV-NET system [104]), communications and education campaigns [105], and changes to patient management protocols within the health system (e.g., increased use of goggles, gowns, masks, and gloves) [106, 107].

Health system strengthening benefits include reduced congestion of healthcare facilities from RSV surges (3.2.1) [94, 108, 109]. The ANC-strengthening investments mentioned above, once incurred, will also yield positive spillovers on downstream ANC services including other maternal vaccines, which can now be provided at lower cost and higher volumes through the increased ANC capacity [64, 103].

Health-Related Benefits to the Broader Population

Potential health-related benefits to populations, broader society, and government include potential MV-induced population-level herd effects (4.1.1), disease control (4.1.2) [60, 107, 110–112], reductions in antimicrobial resistance (AMR) (4.1.3) [113], and health equity benefits (4.2).

Potential population-level herd effects derive from the possibility, yet unconfirmed, of preventing infant infection and transmission discussed in “Infant RSV Disease Treatment, Prevention and Transmission", and the potential household herd effects described in “Health-Related Benefits to Mothers, Parents, Caregivers, and Household Members”, both of which may have spillover effects outside the household. Such population herd effects have been modeled in the literature [54, 59, 60], but currently lack direct confirmation for RSVPreF. In general, disease control can involve eradication, elimination, reductions in endemic incidence and prevalence, or reductions in the probability and scale of outbreaks. In the case of MV, disease control results from both the direct effect of vaccination on infant disease, and potential population-level herd effects. Disease control may manifest in reductions in the probability and scale of RSV outbreaks in neonatal intensive care units (NICUs) [110, 111], other health facilities [107], daycare centers and schools [112], elderly care centers [114], and elsewhere in the general community [115].

Regarding NICUs and other health facilities such as neonatal wards and clinics: reported outbreaks in these settings are few, but this potentially reflects underreporting and underdiagnosis, and may increase with improved diagnostics, surveillance, and reporting practices [107, 116, 117]. Non-preterm births constitute a significant minority of NICU populations (our estimates based on US data suggest 45% [118, 119]), and a majority in well-baby wards. RSVPreF confers protection from birth for these non-preterm births, which directly reduces the incidence and size of RSV outbreaks, and which if such protection extends to infection and transmission, would further allow non-preterm births to break transmission chains in these facilities.

The potential household herd protections described above extend to older siblings, which in turn implies that RSVPreF may reduce outbreak risks in the daycare centers and schools attended by those older siblings. Direct and potential indirect effects from RSVPreF potentially reduce the risk of RSV outbreaks in elderly care settings resulting from sick visitors [114].

The extent of disease control benefits depends on MV’s impact on the probability of the emergence of novel RSV variants, which in theory could be positive or negative. Outbreaks often occur when new disease variants emerge. RSV undergoes ongoing evolution, which is reflected in recurring emergence and disappearance of genotypes [120], and immune pressure has been hypothesized to influence variant emergence [121]. RSV mutation frequencies giving rise to novel genotypes appear to correlate with RSV prevalence [120]. If MV prevents infection and transmission, then it may contribute to reductions in global prevalence and variant emergence. On the other hand, widespread MV may create pressures for the evolution of vaccine resistance. There is some evidence of immune escape RSV variants emerging in response to herd effects from natural immunity [121] and palivizumab administration [122]. However, vaccine escape in general appears historically rare [123]. This is in part because most vaccines like RSVPreF target multiple pathogen epitopes, reducing the probability variants can simultaneously generate all the mutations required to achieve vaccine escape [41, 123].

MV may help reduce AMR by preventing viral disease cases that would otherwise be inappropriately treated with antibiotics [113].

Global RSV burdens are disproportionately borne by LMICs, and national RSV burdens are disproportionately borne by vulnerable populations (as defined by economic deprivation [124], racial minority status [125, 126], household crowding [5], low parental education [5], and receipt of public support [127]). This implies MV has the potential to differentially benefit the worse off globally and nationally, facilitating health equity (4.2).

Broad Benefits to Infants

Regarding broader benefits, there is now an abundant literature documenting the impact of improved health on individuals’ economic well-being [128–141]. In the case of infant RSV disease, potential economic impacts are mediated by potential educational impacts (5.1). These potential educational impacts, in turn, are mediated by infant RSV disease’s potential causal impact on childhood and adolescent asthma, wheezing, allergies, and other chronic respiratory conditions (see Table 1), as well as on neurocognitive and behavioral development [142], all of which have well-known associations with reduced educational attainments [143–146].

Potential MV impacts on infant disease prevention, therefore yield potential educational benefits, which in turn yield potential lifetime productivity benefits (5.2) [147]. These productivity gains span both paid and unpaid work. Paid work benefits (5.2.1) can include reductions in labor market exit, unemployment, absenteeism, and presenteeism (inability to function at full capacity upon returning to work before full recovery). Unpaid work benefits (5.2.2) can include improvements in the ability to perform housework, caregiving, and volunteering. MV-induced infant mortality reductions also avert the lifetime productivity losses from such mortality [148].

The improved lifetime productivity gains from reduced morbidity potentially raise future income (5.3). Income benefits associated with infant health gains also include reduced out-of-pocket (OOP) treatment costs [149, 150]. Infant hospitalization can be associated with considerable, and in some cases, catastrophic OOP costs [150]. In LMICs, for example, OOP costs constitute a large share of total health expenditure [151]. In addition, OOP costs disproportionately burden the poor [152].

Financial risk protection (5.4) is a benefit to risk-averse individuals from reductions in disease-induced uncertainty over OOP costs, income, and expenditures. MV beneficial impacts on productivity and income support future consumption of goods and services (5.5). Reduced disability and mortality also allow infants to enjoy more leisure time over their lifetime (5.6).

Broad Benefits to Mothers, Parents, Caregivers, and Household Members

The above economic benefits can also be received by the parents, household members and caregivers who themselves face lower risks of disease from maternal immunity and reduced intrahousehold transmission. Older siblings may benefit from potential household herd effects and may therefore enjoy educational benefits from MV (6.1). These benefits may come from not having to miss school when sick. They may also come from the hypothesized reduced risks of longer-term sequelae and their adverse educational impacts discussed in “Broad Benefits to Infants”.

Parents and caregivers benefit from reduced caregiving burdens associated with sick infants or household members. These reduced caregiving burdens raise opportunities for paid work (6.2.1) [153] and unpaid work (6.2.2). Income benefits (6.3) reflect increased paid work from reduced caregiver burdens; increased paid work from fewer disease episodes among working-age household members; and reduced OOP treatment costs from fewer disease episodes among household members [94, 95, 154–156]. These fewer disease episodes may in turn reflect possible MV-induced maternal direct protection and potential household herd effects. Households may also benefit from financial risk protection from reduced uncertainty about these financial or income burdens (6.4) [74, 157]. The averted income losses can in turn facilitate consumption (6.5). Averted morbidity and caregiving burdens can facilitate household members’ leisure (6.6).

Broad Benefits to the Broader Population, Society, and Governments

Broad benefits at the population, societal, and government levels include potential fiscal impacts (7.1), and socioeconomic equity (7.2). Fiscal effects include reduced public support [127] and social care costs associated with RSV infections [68, 127, 158]. Socioeconomic equity benefits derive from MV’s averting RSV’s socioeconomic burdens (see “Broad Benefits to Infants” and “Broad Benefits to Mothers, Parents, Caregivers, and Household Members”), which are disproportionately borne by lower-income nations and households [1, 5, 125, 126].

Comparison with Existing Value Frameworks

Columns 2–7 of Table 2 show that many value elements in our taxonomy are described in existing frameworks. However, none of these frameworks contains all the value elements in our taxonomy. Value elements not captured in any of these frameworks include averted bereavement from infant mortality (2.2.3) and the spillover effects of improved ANC systems (3.2.2). The prominent WHO FVVA (Hutubessy et al., 2023 [68]) and Gavi VIS [67] frameworks also omit the peace of mind that parents gain from a reduction in the risk that their infant will become infected (2.2.1) and averted mental and physical burdens of caring for a sick infant (2.2.2).

Discussion and Conclusion

Our taxonomy attempts to represent the full health and societal value of MV. This taxonomy can assist decision-makers’ assessments of the value of MV by calling attention to its elements, supporting their quantification, supporting their qualitative consideration where quantitative estimates are missing, and supporting further research.

Many important value elements are narrow health benefits and can therefore be considered by decision-makers adopting a narrow health-centric value perspective. However, many other important value elements are broad, including impacts on education, productivity, income, financial risk protection, leisure, consumption, daycare and school closures, and socioeconomic equity. These elements suggest that optimal coverage and investment in MV will likely be facilitated by adopting a broad value perspective.

Many value elements are globally relevant, such as infant morbidity reductions; maternal, caregiver, and household health and socioeconomic benefits; health system cost reductions; public health effects; and health and socioeconomic equity. Other elements are disproportionately relevant in LMICs, including infant mortality reductions and reducing OOP costs and financial risks. Of special relevance to LMICs is the relative underdevelopment of ANC. On the one hand, this can be an obstacle to achieving MV coverage goals. On the other hand, investments in ANC to support MV would have spillover benefits for other ANC services and maternal vaccination programs.

The magnitudes of these value elements will vary across countries and depend greatly on vaccine effectiveness and uptake. Many narrow and broad value elements can be quantified using traditional VfM measures such as the incremental cost-effectiveness ratio. They therefore do not require methodological innovation to be considered in decision-making. These elements include any mortality or morbidity reduction impacts on infants, children, and adults that can be transformed into quality-adjusted life-years (QALYs) or disability-adjusted life-years (DALYs); any savings in treatment costs faced by health payers and households (e.g., OOP costs); public health cost savings; and indirect cost savings (e.g., productivity losses). Sources of country-specific estimates of these quantities at varying levels of effectiveness and immunization coverage are provided in Table 2 [81, 96, 159–161]. Other value elements (e.g., risk protection, equity) may require methodological innovation, but such innovation is ongoing [70]. Many narrow and broad value elements require relatively standard data (e.g., QALYs, DALYs, treatment and productivity costs), but other elements are more difficult to quantify because of data requirements (e.g., potential herd effects and AMR reduction).

Optimal funding and coverage decisions regarding MV depend not only on its broad value but also on its price. They also depend on the VfM of alternatives such as mAbs, which, for consistency, should also be evaluated broadly. Our taxonomy supports optimal assessments of the value of MV and therefore contributes to optimal decisions regarding its use.

Author Contributions

Conceptualization: JP Sevilla, David E. Bloom; Writing – Original Draft Preparation: JP Sevilla, Daria Burnes, David E. Bloom; Writing – Review & Editing: JP Sevilla, Daria Burnes, David E Bloom; Visualization: Daria Burnes; Supervision: JP Sevilla, David E. Bloom; Project Administration: JP Sevilla, David E. Bloom; Funding Acquisition: David E. Bloom.

Funding

This study was sponsored by Pfizer Inc through a contract with Data for Decisions, LLC. An award or grant number is not applicable. The journal’s Rapid Service fee was enabled and organized by Pfizer Inc.

Data Availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Declarations

Conflict of Interest

JP Sevilla and Daria Burnes are employees of Data for Decisions (DfD), and David Bloom is an external consultant to DfD. DfD received funding from Pfizer in connection with the development of this manuscript and the conduct of the study on which it is based. JP Sevilla and Daria Burnes in their capacities as employees at DfD and David Bloom in his capacity as an external consultant to DfD have worked on other studies funded by grants from Pfizer to DfD. JP Sevilla and David Bloom in their personal capacities have received compensation, including expense reimbursement, from Pfizer Inc for providing consulting services and for speaking and participating in meetings and advisory boards.

Ethical Approval

This article is based on previously conducted studies and does not contain any new studies with human participants or animals performed by any of the authors.