Understanding the impact of adult pertussis and current approaches to vaccination: A narrative review and expert panel recommendations

ABSTRACT

Pertussis has several notable consequences, causing economic burden, increased strain on healthcare facilities, and reductions in quality of life. Recent years have seen a trend toward an increase in pertussis cases affecting older children and adults. To boost immunity, and protect vulnerable populations, an enduring approach to vaccination has been proposed, but gaps remain in the evidence surrounding adult vaccination that are needed to inform such a policy. Gaps include: the true incidence of pertussis and its complications in adults; regional variations in disease recognition and reporting; and incidence of severe disease, hospitalizations, and deaths in older adults. Better data on the efficacy/effectiveness of pertussis vaccination in adults, duration of protection, and factors leading to poor vaccine uptake are needed. Addressing the critical evidence gaps will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to healthcare professionals, policymakers, and payers.

KEYWORDS:

• Bordetella pertussis
• disease burden
• underreporting
• Tdap vaccination
• adults

Introduction

Pertussis is a highly contagious respiratory infection caused by the bacterium Bordetella pertussis and commonly characterized by severe, repeated coughing episodes.^1,2 It is a worldwide public health problem and a notifiable disease in many countries.^3,4

Pertussis accounts for a significant level of morbidity and mortality in infants who are too young to be vaccinated worldwide, despite high levels of pediatric vaccination coverage.³ Although widely considered a childhood illness, the age distribution of clinically significant pertussis reported in recent years has been changing in countries with high primary vaccination coverage.^3,5 Reported cases increasingly involve older children and adults, particularly where acellular pertussis (ap) vaccines have replaced whole-cell pertussis (wp) vaccines for primary vaccination.^3,5 Although case notifications and seroprevalence data provide an indication of this evolving epidemiologic pattern, the true burden of pertussis in adults is unknown due to lack of recognition and underreporting in clinical practice.^3,6 Pertussis can have severe and sometimes fatal consequences in adults, and is associated with a significant detrimental impact on quality of life, and substantial healthcare utilization and costs.^7–11

An enduring (lifelong) approach to pertussis vaccination has been proposed to increase immunity and reduce disease burden in all age groups, while helping to decrease the risk of transmission to unvaccinated infants and other vulnerable populations.^6,12 However, universal adult vaccination recommendations have not been adopted consistently or funded even in high-income countries. Where recommendations are in place, evidence of low uptake is common.^13–16

A previous publication examined methods to improve pertussis vaccination in at-risk groups including older adults.¹⁷ The current publication, developed by an international panel of pertussis experts, builds on that article to provide up-to-date perspectives on the burden of pertussis in adults, identify current gaps in the evidence around adult Tdap vaccination, and lay out recommendations for future research directions.

Methods

In July 2022, an academic panel was assembled to discuss their views on the evolving epidemiology of B. pertussis infection and the need for adult pertussis vaccination. The panel consisted of 24 renowned national and international experts in pertussis and vaccination from 14 countries.

The panel discussion was organized by Sanofi, took place during seven virtual meeting sessions, and via an online discussion platform. Discussion was facilitated by open-ended questions relating to potential knowledge gaps and practical challenges in adult pertussis illness and pertussis vaccination in adults, with a goal of driving development of expert recommendations on how gaps might be addressed. This manuscript summarizes the panel’s positions and recommendations, which are informed by key peer-reviewed publications, surveillance data, and health authority assessments, as well as real-world experience.

Etiology, transmission, pathogenesis, and presentation of pertussis disease

Pertussis (whooping cough) is an ancient, contagious respiratory infection caused by the aerobic Gram-negative bacterium Bordetella pertussis, with other Bordetella species (e.g., B. parapertussis, B. holmesii) also causing pertussis-like symptoms.^1,2,18,19 The incubation period is typically 7–10 d (range: 4–21 d).¹

Transmission most commonly occurs from human to human via contact with infectious airborne respiratory droplets from a cough or sneeze, and requires repeated or prolonged exposure and/or close contact.^1,20 Attack rates for nonimmune contacts in the household setting have been estimated at up to 90%,²¹ and inoculation studies show that as few as 140 organisms are required to infect susceptible people.²⁰

While the molecular pathogenesis of pertussis is not completely understood, the disease appears to be primarily toxin driven, as B. pertussis creates various biologically active and antigenic products, including filamentous hemagglutinin (FHA), pertactin (PRN), and pertussis toxin (PT).¹ These toxins are released when the bacteria attach to cilia of the respiratory system mucosa, paralyzing the cilia and causing inflammation in the respiratory tract.¹ Clearance of pulmonary secretions is subsequently impeded, leading to the classic symptoms of pertussis: paroxysms of rapid coughing, ending with a long inspiratory whoop (i.e., “whooping cough”), post-tussive apnea, and post-tussive emesis.^1,8 The molecular pathogenesis of pertussis has been investigated in infants, for whom disease is severe.²² Adolescents and adults less often present with the classic symptoms of pertussis, because they are usually milder than in children,¹⁷ yet there are limited data available on the pathology of mild or typical pertussis in adults.²³

Current understanding of the epidemiology of adult pertussis and burden of disease

Incidence, lack of recognition, and missed diagnosis

Despite a general trend of increased childhood pertussis vaccination rates globally in recent years and declines in disease in this age group since the pre-vaccine era, pertussis remains a threat to public health.^3,24 It is an endemic disease, with cyclical outbreaks typically seen every few years and a higher incidence reported in the summer months.^18,25,26 The seasonality of pertussis remains unexplained.²⁵ Outbreaks among adolescents and adults are commonly associated with school and workplace settings, but may also occur in elderly residents of care homes.^8,27,28

The epidemiology of pertussis among all age groups is not well known; there is a lack of global surveillance data for pertussis, as many countries have neither obligatory notification nor national reporting systems in place.²⁹ Data collected by global and local authorities over the past four decades highlight the growing burden of pertussis (Table S1). Even though pertussis is a notifiable disease in some countries, reported case rates are much lower than actual true incidence rates due to lack of recognition, missed diagnosis, and underreporting in clinical practice (Table S1).^6,7,30

Failure to recognize pertussis has critical consequences, as timely diagnosis, isolation, and treatment of pertussis are needed to mitigate transmission to vulnerable populations and minimize potential disease complications.^1,31 Moreover, pertussis is a relatively long-lasting, but frequently self-limiting disease in adolescents and adults, thus there is a large gray area in terms of reporting disease. Several analyses of pertussis incidence over the past 40 y have indicated a resurgence in reported cases in high-income and many middle-income countries (Table S1), as well as a shift toward an increase in reported cases among adolescents and adults following widespread routine pediatric vaccination.^4,5,32–35

The trend of an increase in adult pertussis is concerning, especially as a shift in peak incidence to include women of child-bearing age may increase the risk of infection among newborns and unimmunized infants, who are at highest risk of significant morbidity, hospitalization, and death due to pertussis.^36–39 Data on pertussis in pregnant women are limited, but one US case surveillance study – conducted after maternal Tdap vaccination during pregnancy had been introduced – found similar reported rates of pertussis between pregnant and non-pregnant women.⁴⁰ Infection in older adults is also a concern because they may suffer serious complications and loss of independence, but could also be involved in grandparent care of vulnerable infants. Consequently, vaccination could prevent pertussis spreading to very young grandchildren.

Various factors probably contribute to the observed upward trends in pertussis incidence and affected older age groups, including increased awareness of the disease, developments in diagnostics, aging populations with waning immunity against B. pertussis, and pathogen adaptation perhaps caused by vaccine-driven immune selective pressure.^{32–34,36,40} The relative contribution of these factors to the changing epidemiology of pertussis disease may differ between and within regions and countries.³²

A 2019 systematic literature review of pertussis epidemiology in adults (≥40 y old) demonstrated that numbers of notified cases based on surveillance data were consistently and significantly (several hundred- or even thousand-fold) lower than seroprevalence data indicative of B. pertussis infection.⁷ As well as being dependent on level of care-seeking, underreporting of pertussis in adults may in part be due to the atypical nature of adult disease, in which the classic symptom of whooping may often be absent. Pertussis may therefore not be considered a likely cause by healthcare professionals (HCPs) when evaluating subacute cough in older age groups, despite evidence of B. pertussis infection reported in approximately 20% of adults presenting with a persistent (7–31 d) cough and no evident diagnosis.^22,41

A failure to recognize pertussis may be particularly important in adults with respiratory comorbidities, such as asthma and chronic obstructive pulmonary disease (COPD), due to similarities in clinical presentation with characteristics of these conditions (e.g., persistent cough); acute pertussis may be misinterpreted as a COPD or asthma exacerbation, leading to delayed or missed diagnosis.^11,42,43 Data from a seroprevalence study in adults 40–85 y of age with COPD indicate high circulation rates of B. pertussis in this subgroup (evidence of exposure to B. pertussis in 13.5% of patients over two years), adding to data from other studies suggesting an increased risk of B. pertussis infection and disease in adolescents and adults with COPD or asthma.^43–46

Impact of adult pertussis

Disease presentation

A better insight into the signs and symptoms, and course of pertussis disease in adults could help HCPs differentiate it from other common causes of cough and ensure prompt diagnosis. However, these aspects of pertussis have not been well documented; symptoms can vary widely between age groups and throughout the disease course, making diagnosis based on clinical presentation challenging.^7,8,47

Early symptoms in older, vaccinated adolescents and adults are frequently mild and similar to those of the common cold.¹ Conversely, delayed diagnosis and treatment of adult pertussis can result in clinical complications, sequelae, and an increased risk of transmission within households or semi-closed communities (e.g., nursing homes), adding to the individual and societal burden of disease. Pertussis-linked symptoms and the associated complications from delayed diagnosis and treatment are summarized in Table 1. It should be noted that the proportion of cases with more than one disease complication is typically greater among adults than adolescents (28% vs. 16% in one study).⁸

Table 1. Pertussis is associated with a multitude of symptoms, and complications from delayed diagnosis and treatment.

Classic symptoms^Citation1–7,Citation8–10,Citation22,Citation48–53	Secondary symptoms^Citation10,Citation53	Reported complications from delayed diagnosis and treatment^Citation1,Citation7,Citation8,Citation22,Citation48,Citation54
Persistent cough* (mean duration 10–12 weeks^†) Paroxysmal in 99% of cases Whoop Post-tussive emesis Feelings of suffocation Fainting from cough	Rhinorrhea Pharyngitis Sweating attacks Fever Fatigue	Sinusitis Otitis media Urinary incontinence Pneumonia Weight loss Rib fracture Cough syncope Conjunctival hemorrhage Stroke Encephalitis Seizures Rectal prolapse

*Many adolescents and adults with serological evidence of recent B. pertussis infection do not report persistent cough.^1,7,8,22,48

^†Pertussis recovery time may be prolonged, with symptoms reportedly lasting up to 6 months.^10,53

Severe disease, hospitalizations, and mortality

A range of factors, including a patient’s age and immunocompetence, and previous immunizations and B. pertussis infections, can influence the severity of pertussis symptoms and associated healthcare needs.²² In one analysis, nearly half of surveyed adolescents and adults with pertussis rated the severity of their disease as ≥8 on a scale of 1 (very mild) to 10 (the most severe disease), and pertussis-related illness was reported to have disturbed a median of 14–21 nights of sleep.⁸

A recent literature review indicated that adolescents and adults with underlying conditions, such as asthma, COPD, obesity, or immunodeficiency, and/or past smokers, are potentially at increased risk of worsened symptoms and pertussis-related hospitalization.⁶ Older adults frequently have chronic comorbidities such as asthma, COPD, or other respiratory diseases, so it is unsurprising that studies suggest severe pertussis sequelae (e.g., pneumonia as a secondary diagnosis) and pertussis-related hospitalizations increase with age^8,9,39 (Table 2). In addition, the length of hospital stays and the proportion of pertussis-related mortalities have also been suggested to increase with age (Table 2). It is also to be expected that complications arising from severe paroxysmal coughing, such as encephalopathy, intracranial hemorrhage, and herniated lumbar discs,²² may be recorded as the cause of hospitalization, without mention of pertussis.

Table 2. The proportion of pertussis-related hospitalizations, fatalities, and the length of hospital stays increase with age.^7,8,34,39,46.

Hospitalization proportion*		Mean length of hospital stay		Case-fatality rate^†
Age group	%	Age group	Days	Age group	%
Adolescents and adults	1–3^Citation8,Citation39,Citation46	<50 years	3^Citation8	18–64 years	11.5^Citation34
≥75 years	11–14^Citation8,Citation39,Citation46	>50 years	17^Citation8	≥65 years	17.4^Citation30‡

*Pertussis-related hospitalizations (particularly for patients with chronic diseases, where the chronic disease is likely to be documented as the cause of hospitalization despite pertussis symptoms being present).

^†Pertussis-related fatalities are likely to be underestimated due to the acknowledged underreporting of the disease.⁷

^‡Adults ≥65 y.

Economic impact

Healthcare utilization and related costs associated with adult pertussis are substantial, particularly in adults ≥65 y old and/or those with underlying respiratory conditions, such as COPD or asthma.^9,22,44,55 Furthermore, the household and societal economic burdens linked to adult pertussis often arise from direct and indirect healthcare costs (Table S2).

Impact on quality of life

Pertussis can have a serious, detrimental impact on the quality of life of infected adults and increase risk of dependency for activities of daily living.^10,11 Persistent, severe cough has been identified as the main cause of lost quality of life in adults with pertussis, since it affects sleep, and induces vomiting and tiredness.^10,56 In a large UK study that analyzed EQ-5D questionnaire responses among confirmed pertussis cases following the 2011–2012 outbreak, the authors observed that pertussis impacts a range of quality-of-life dimensions (as shown in Figure 1) and concluded that the adverse impact of pertussis on quality of life was about 10-fold greater than that reported in a similar study of influenza.^10,57

Figure 1. Questionnaire responses among school-age children and adults highlight the negative impact pertussis may have on quality of life.¹⁰.

*Data from a large UK study that analyzed EQ-5D (QoL questionnaire with a 5-dimension scale) responses.¹⁰ QoL, quality of life.

Data gaps and evidence generation

Epidemiology and burden: key evidence gaps

Several knowledge gaps in the epidemiology and burden of adult pertussis and their associated drivers were perceived by the panel (Table 3). A key example is the suitability of laboratory detection methods, which vary at different times in the disease course of pertussis (Figure 2).

Figure 2. The optimal timing for pertussis diagnostic testing is dependent on the stage of disease.

Adapted from https://www.cdc.gov/pertussis/about/signs-symptoms.html.

PCR, polymerase chain reaction.

Table 3. Knowledge gaps in the epidemiology and burden of disease identified by the panel and their associated drivers justify the importance of adult pertussis vaccination.^4,7,58.

Identified knowledge gap	Drivers
Data on the true disease incidence and its complications in adults	Lack of targeted, systematic testing in adults Testing has little relevance to guide treatment, particularly for patients presenting late after the onset of coughing Results only become available within 1–2 weeks of disease onset, before paroxysms occur, thus demotivating the utilization of tests^Citation31 The availability and suitability of laboratory detection methods varies at different times in the disease course and in different populations (see Figure 2) Limitations of the detection techniques and cut-offs currently employed Local financial constraints on testing in different settings
Regional variations in disease recognition and reporting in adults	Surveillance approaches can be insensitive and may vary widely among and within countries^Citation4,Citation7,Citation59 Variations in the case-ascertainment method (laboratory confirmed or just clinically defined) Variations in laboratory testing methods Variations in case definition Variations in the age-groups reported Presence/absence of active sentinel surveillance
Incidence of severe disease, hospitalizations, and deaths in older adults	Under ascertainment of death rates or hospitalizations, or the impacts of pertussis in individuals with comorbidities^Citation7 Prevents comparisons of the risks of these outcomes relative to other health conditions (e.g., pneumonia or myocardial infarction)

The panel also concluded that to help create a better understanding of the burden of disease, additional evidence is needed on the broader individual and societal impacts of pertussis in the general adult population. A range of readily measurable impacts were identified by the panel as having strong potential for justifying a change in adult vaccination policy (Table S3). Overall, a detailed understanding of the burden of disease is a prerequisite for informed decisions regarding vaccination strategies.

The concept of an adverse long-term impact of other acute infections, such as RSV and SARS-CoV-2, has been established via studies in older/at-risk patients. These studies demonstrated a significant long-term worsening in health-related quality of life and frailty post infection, which was independent of potential confounders, such as age and comorbidities.^59–61 Some panel members positioned similar research as a priority for understanding the burden of adult pertussis.

Incidence of subclinical or asymptomatic adult pertussis infection is another important yet understudied topic identified by panel members. Such infections are a public health consideration, as asymptomatic carriers of B. pertussis do not alter their behavior to prevent disease transmission. As humans are the only source of pertussis, some asymptomatic adults could represent a highly significant reservoir of infection. Prevalent asymptomatic infection may also explain the finding of broad immunologic reactivity to hundreds of non-ap B. pertussis antigens seen in a recent full genome analysis of healthy ap-vaccinated adults.⁶² While the formation of bacterial biofilms, which are resistant to host defenses, has been proposed as a mechanism for chronic and asymptomatic respiratory tract colonization of Bordetella spp. in mammals,⁶³ the panel noted a current absence of evidence on the role of biofilms in B. pertussis infection and transmission in humans.

Epidemiology and burden: future research directions

Various approaches to evidence generation were proposed by the panel to address knowledge gaps in the epidemiology and burden of adult pertussis (Table S4). Panel members agreed that the highest priority was to conduct a prospective, observational global study of adults presenting with cough of unknown origin and/or respiratory symptoms (see Figure 3 and Table S4). Most panel members agreed this approach had high feasibility based on similar studies on pertussis,^64,65 and for other pathogens,^66–68 and would be high impact, in terms of providing useful data to address current gaps in understanding of the incidence and impact of adult pertussis disease. Furthermore, the panel recommended the inclusion of sensitivity analyses in future models that reflect a range of different scenarios, prior to conducting rigorous active surveillance studies to validate the models.

Figure 3. Panel recommendations for the design of a large prospective study assessing the incidence and impact of adult pertussis.

*Mixed views among panel members: some felt important to include, others felt not a priority unless searching for secondary cases. ^†Independent of severity. ^‡Both outcomes were felt to be important by several panel members, but in some cases may be difficult to adequately differentiate.

GP, general practitioner; HIC, high-income country; LMIC, low-to-middle-income country; PCR, polymerase chain reaction; QoL, quality of life; SARS-CoV-2, severe acute respiratory syndrome coronavirus 2.

Pertussis vaccination in adults: key evidence gaps

Panel members had differing opinions on whether the available literature accurately reflects the true benefits of Tdap vaccination in adults. Important data gaps regarding the efficacy/effectiveness of pertussis vaccination in adults remain and represent a barrier to wider implementation by policymakers. The panel emphasized that data are needed on the efficacy/effectiveness of adult vaccination in preventing pertussis-related hospitalizations, severe disease, and death, most notably in at-risk subgroups, for whom evidence of Tdap efficacy is critical. Generating robust data on these outcomes was seen as a major priority, alongside information on the safety of vaccination in older adults and those with underlying comorbidities.

The duration of protection afforded by vaccination must be evaluated, both in the general adult population and in at-risk groups. Such data are vital for designing rational, effective pertussis-containing booster vaccination programs for adults. The panel also noted that information on the immunogenicity of multiple Tdap boosters in adults is needed, including confirmation of whether immune tolerance develops over time in older adults – who are likely to have been primed with the wp vaccine – with repeat ap booster vaccinations. Older adults will typically have had asymptomatic B. pertussis infections during their lifetime, and the impact of immunosenescence and escape variants on Tdap booster efficacy in this population is unknown. Indeed, evidence from a recent analysis of the benefit of performing adult booster vaccinations against tetanus and diphtheria have raised questions on the rationale for combining these with pertussis boosters and the potential need for a standalone adult pertussis vaccine.^69,70

While some research has been undertaken on the transmission dynamics of pertussis using passive surveillance,^71,72 patterns of transmission in older adults are not currently understood. The panel noted that research in this area is required to determine any indirect effects of adult Tdap vaccination on interrupting transmission and establish the most effective timing for administering adult boosters. Consideration of living arrangements and close contacts should lead to a study of household pertussis transmission and carriage.

Factors underlying the lack of uptake of adult Tdap vaccine, including among pregnant women, is another area identified by the panel as lacking in data. Implementation research is needed to understand why current adult pertussis vaccination recommendations are not more widely adhered to in routine practice,^13–16 and to provide insights on how HCP and organizational behavior can be evolved toward improved implementation practices. Further evidence generation around Tdap vaccination in underserved groups of adults, including the effects of population demography on disparities in uptake, would also help to inform the direction that needs to be taken to optimize uptake implementation strategies.

Pertussis vaccination in adults: future research directions

A range of approaches to evidence generation were assessed by the panel when considering how to address the knowledge gaps around adult Tdap vaccination strategy (Table S5). These approaches included:

• Prospective, observational cohort studies, including studies focused on evidence generation in at-risk populations, such as COPD and asthma sufferers (either separate studies, or via subgroups in larger studies in the adult population)

• Case – control studies (vaccinated vs. non-vaccinated and/or non-boosted adults) in patients hospitalized with pertussis, stratified by age; ideally conducted during an outbreak

• Prospective, parallel data collection on pertussis disease burden and vaccination history; ideally executed in countries that have both adult Tdap recommendations and well-documented vaccination records

• Retrospective analyses of electronic healthcare records where databases can be linked, e.g., hospitalized patients in settings with adult Tdap recommendations and acceptable vaccine coverage

• Seroprevalence studies – most panel members felt such studies would have little impact on vaccination policy, where a focus on prevention of severe disease is the priority

• Cost-effectiveness analyses (including impact on indirect costs and quality of life) – critical for policy-making and public funding; however, robust data on Tdap efficacy/effectiveness and the true burden of adult disease are essential before undertaking such analyses

• Contagiosity studies – to investigate how easily pertussis is spread following index cases

On considering the potential approaches to studying Tdap efficacy/effectiveness in adults (Table S5), the panel agreed that a randomized, controlled trial evaluating the efficacy of vaccination on severe pertussis disease versus standard of care (as use of a placebo could be considered unethical) is likely to have the maximum impact on national vaccination recommendations. Agreed requirements for such a study included both a clinical diagnosis of pertussis and polymerase chain reaction (PCR) confirmation of B. pertussis infection, as well as the documented vaccination history of study participants. In the absence of a randomized study, real-world evidence from regions with a recommendation for adult Tdap vaccination, using a cohort or test-negative case-control study design, could also generate estimates of Tdap effectiveness and cost-effectiveness that could be used for policy decision-making.

To help address the current data gap on duration of protection from adult Tdap vaccination and determine the optimal timeframe for booster vaccinations, the panel proposed a modeling study. The typical recommendation for a 10-year booster interval for Tdap is historically based on presumed protection against tetanus, rather than on evidence demonstrating adequate protection for pertussis.

Future directions in pertussis vaccine research and development

Although not completely understood, the resurgence of pertussis seen in recent decades in many high- and middle-income countries with high vaccination coverage has been widely linked to the replacement of wp vaccines with ap vaccines in the 1990s.^73–75 However, there is evidence from a recent collaborative study of Central and Eastern European countries that this might not be true.⁷⁶ Whilst both ap and wp vaccines induce durable protection from symptomatic disease, the mechanisms initiated to achieve this differ (Table 4). Indeed, several preclinical studies and exploratory analyses of blood samples from vaccinated human subjects have revealed distinct differences in T- and B-cell immune responses induced by ap and wp vaccines, depending on the type of vaccine used for initial priming and for subsequent booster vaccinations (see Szwejser-Zawislak et al. for a recent systematic review on this topic).⁷⁷

Table 4. Wp and ap vaccines induce durable, but distinct immune responses.^73,78,79.

Immunity	wp vaccine	ap vaccine
Confers persistent protective immunity against asymptomatic colonization of the airways or prevents transmission of B. pertussis to unvaccinated contacts?^Citation73,Citation78,Citation79	Yes*	No*
Type of Th immunity induced^Citation78	Th17 and Th1 (correlate with the ability to clear infection)	Th2 and Th1 (memory responses)

*Inference made using data collected from animal models.^73,78,79

ap, acellular pertussis; Th, t helper; wp, whole-cell pertussis.

Based on these observations, development of next-generation pertussis vaccines capable of inducing protective immunity in the respiratory tract, as well as the optimal design of life-course vaccination strategies, are now high priorities on the research agenda. The panel, however, noted important gaps in understanding that will need to be addressed to expedite these research goals, and effectively bridge the findings from animal model research to clinical trials in humans,^78–82 including:

• Mechanistic understanding of vaccine- and infection-induced immunity to pertussis in humans, including memory imprinting of cellular immune responses in the nasal mucosa against asymptomatic infection

• Identification of biomarkers that correlate with protective immunity against asymptomatic infection and transmission in humans and which can be readily evaluated in vaccine trials

• Development of a safe and reproducible model of B. pertussis infection in humans to facilitate ethical, compelling human challenge studies that evaluate nasopharyngeal colonization with B. pertussis as an endpoint.

The panel acknowledged emerging approaches to inducing potent cellular immune responses in the respiratory mucosa, with potential to improve protective local pertussis immunity in humans. These strategies include novel vaccine delivery methods, such as vaccine antigens entrapped in biodegradable microparticles,⁸³ and investigational vaccine candidates, including ap vaccines formulated with novel Th17/Th1-skewing adjuvants,⁸⁴ outer membrane vesicle (OMV) vaccines,⁸⁵ and live attenuated vaccines.⁸⁶ Among all candidates to date, only BPZE1, a nasally administered live attenuated pertussis vaccine, has advanced into clinical development. A recent proof-of-concept study in healthy, mostly wp-primed, adults, showed that BPZE1 could induce nasal secretory IgA responses and serum IgG responses against B. pertussis antigens, indicating potential for protective immunity in humans against asymptomatic infection and transmission.⁸⁷

It was also noted how the scope of future potential pertussis vaccine technologies has been broadened by the COVID-19 pandemic. The significant pace of SARS-CoV-2 vaccine research stimulated a range of novel vaccine development approaches – such as nucleic acid-based and recombinant viral vector-based vaccine platforms – that may also have potential for the development of next-generation pertussis vaccine candidates.⁸⁸

Concluding remarks

The resurgence in pertussis cases reported in many countries over the past few decades has highlighted a need to revisit adult pertussis vaccination recommendations (which are frequently absent or inconsistent), address barriers to uptake, and generate appropriate supporting evidence. In their review and appraisal of the current adult pertussis vaccination landscape, the expert panel identified differing data needs among countries that already have adult Tdap recommendations in place, and those that do not. For countries with established recommendations, generation of compelling evidence in areas such as vaccine efficacy/effectiveness and protection duration are needed to motivate HCPs to deliver adult Tdap vaccination and encourage the public to seek it. Where recommendations for adult vaccination do not exist, there is a requirement for convincing evidence of the need to protect adults from pertussis disease, based on a realistic understanding of its current epidemiology, burden, and impact in both the general population and at-risk groups, as well the value of broader immunization of the adult population in reducing transmission from carriers with asymptomatic infection to unvaccinated infants and other vulnerable populations. Addressing these critical evidence gaps and driving a deeper understanding of these factors will help highlight important areas of unmet need and justify the importance of adult pertussis vaccination to HCPs, policymakers, and payers.

Author contributions

In July 2022, 24 international academic experts convened to discuss the challenges associated with the detection, monitoring, and vaccination of pertussis in adults. Authors listed are those who wished to develop two publications associated with the discussions. Given the nature of discussions, all authors contributed to the paper equally. It was agreed that Dr Peter Kardos would take overall responsibility and serve as lead and corresponding author; all other authors are listed alphabetically.

The second publication is titled: ‘Public health management of pertussis in adults: practical challenges and future strategies,’ authored by Professor C Raina MacIntyre, Dr Jaime Correia de Sousa, Professor Ulrich Heininger, Dr Peter Kardos, Professor Andreas Konstantopoulos, Dr Donald Middleton, Professor Terry Nolan, Professor Alberto Papi, Dr Adrian Rendon, Dr Albert Rizzo, Mr Kim Sampson, Dr Alessandro Sette, Ms Elizabeth Sobczyk, Dr Tina Tan, Professor Catherine Weil-Olivier, Dr Birgit Weinberger, Professor Tom Wilkinson, and Dr Carl Heinz Wirsing von König.

Acknowledgments

Medical writing support funded by Sanofi was provided by Caroline Minshull of Inizio Medical who captured the outline, wrote the initial draft of the manuscript based on the discussions of the authors, and incorporated comments from the authors.

Disclosure statement

PK received honoraria for participating in the 2022 Zoom meetings by Sanofi; he also received honoraria for participation in advisory boards and lectures, and travel costs from the following companies: AstraZeneca, Bionorica, Chiesi, Engelhard, GSK, Janssen, Klosterfrau, Novartis, MSD, and Schwabe. His institution received honoraria for clinical trial participation from Bellus, the ERS NEuroCOUGH Initiative, and MSD. JCS received research support from AstraZeneca and GSK; and honoraria from AstraZeneca, GSK, Bial, Sanofi, and Medinfar, He also participated in a company-sponsored speaker’s bureau for AstraZeneca and Sanofi. UH received consulting fees from Sanofi and GSK, and lecture fees from GSK, Infectopharm, Merck, Moderna, Pfizer, Roche, Sanofi Genzyme and Sanofi-Pasteur. He participated on the Data Monitoring Committees of a poliomyelitis vaccine (Takeda), a phase II study of an adjuvanted pandemic influenza vaccine (GSK/Watermark), the Norovirus Bivalent VLP Vaccine Program (Takeda/HilleVax), and the Cell culture influenza vaccine (Seqirus/IQVIA). He is a member of the Meta Data Safety Monitoring Board for CEPI (Coalition for Epidemic Preparedness Innovations) and of the Varicella Advisory Board, Switzerland (Merck). CRM is supported by an NHMRC Investigator Grant, grant no. [2016907]. She is on the WHO COVID-19 Vaccine Composition Technical Advisory Group and the WHO SAGE Working Group on Smallpox and Monkeypox. She currently receives funding from Sanofi for influenza and pertussis research. DM received personal fees from Dynavax, Seqirus, Sanofi, and GSK; and grants and personal fees from Pfizer. TN received research contracts to conduct clinical trials, with funding to the institution from Moderna, Sanofi, GSK, Iliad Biotechnologies, Dynavax, Seqirus, Janssen, and MSD; consulting fees from GSK, Seqirus, MSD, Sanofi, AstraZeneca, Moderna, BioNet, and Pfizer; and has served on data safety and monitoring boards for Seqirus, Clover, Moderna, Emergent, Serum Institute of India, SK Bioscience Korea, Emergent Biosolutions, and Novavax. AP received grants or contracts from Chiesi, AstraZeneca, GSK, Sanofi, and Agenzia Italiana del Farmaco (AIFA); consultancy fees from Chiesi, AstraZeneca, GSK, Novartis, Sanofi, Avillion, and Elpen Pharmaceuticals; payment or honoraria for lectures, presentations, manuscript writing or educational events from Chiesi, AstraZeneca, GSK, Menarini, Novartis, Zambon, Mundipharma, Sanofi, Edmond Pharma, Iqvia, Avillion, and Elpen Pharmaceuticals; and participated on a data safety monitoring board or advisory board for Chiesi, AstraZeneca, GSK, MSD, Novartis, Sanofi, Iqvia, Avillion, and Elpen Pharmaceuticals. AR received consulting fees, honoraria for lectures, presentations, speakers’ bureaus or educational events, and participated in advisory boards from AstraZeneca, Boehringer Ingelheim, Chiesi, GSK and Sanofi; and received support for travel/attending meetings from Chiesi. KS received a salary from the Australian Immunisation Coalition which has received funding towards some of its activities from industry sources, including GSK, Sanofi, Roche and Seqirus. He also received a consultancy fee from APACI, which derives its income from similar sources. AS is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. La Jolla Institute for Immunology has filed for patent protection for various aspects of T cell epitope and vaccine design work. TT received grants from Merck and Sanofi; personal fees from GSK Biologicals and Sanofi; and honoraria from Sanofi. CWO received grants/contracts and payment/honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events from AstraZeneca, GSK, Janssen, MedImmune, Pfizer, Sanofi, and Sanofi-Aventis; consulting fees, acting as a punctual consultant or directly as an independent expert, from AstraZeneca, GSK, Janssen, MedImmune, MSD, Pfizer, Sanofi, and Sanofi-Aventis; and acted in a leadership or fiduciary role for Coalition for Life Course Immunisation and Infovac-France. BW received honoraria for participation in advisory boards and lectures, and travel costs from the following companies: GSK, MSD, Sanofi, Moderna. TW received research funding and consultancy fees from Synairgen Research Ltd. CHWVK received honoraria for attending meetings sponsored by Sanofi, GSK Biologicals and MSD. AK, AAR, and ES have no competing interests to declare.

Supplementary material

Supplemental data for this article can be accessed on the publisher’s website at https://doi.org/10.1080/21645515.2024.2324547.

Additional information

Funding

This work was supported by Sanofi. However, Sanofi was not involved in the development of this manuscript. The opinions and views expressed in this manuscript are solely those of the authors and do not reflect the position of Sanofi.