Acellular Pertussis Vaccines Show Strong Early Protection but Waning Immunity

Pertussis remains one of the most stubborn vaccine-preventable respiratory diseases, and a new narrative review published in Frontiers in Microbiology takes stock of how acellular pertussis vaccines are performing across the populations that receive them most often: infants, children, adolescents, adults and pregnant women. The review, written by researchers at the National Institutes for Drug Control in Beijing and collaborators, synthesizes representative clinical evidence on effectiveness, immunogenicity and safety rather than attempting an exhaustive comparison of every product on the market. Its central picture is one of genuine achievement shadowed by persistent challenges. Acellular vaccines have largely replaced reactogenic whole-cell formulations in many countries, and three-component or higher acellular vaccines have shown efficacy of approximately 84–85% against typical childhood pertussis. Yet protection after infant DTaP wanes over time, antigen-deficient circulating strains are emerging, and the vaccines’ limited effects on nasopharyngeal colonization have renewed scientific interest in antigen composition, immune mechanisms and clinical protection.

The defining feature of acellular pertussis vaccines is their use of selected protective antigens of Bordetella pertussis rather than whole inactivated bacteria. Pertussis toxin, or PT, is the central antigen in currently licensed and investigational acellular vaccines; as an important virulence factor that mediates multiple systemic pathological effects, anti-PT antibodies are widely used as a core indicator of vaccine-induced immunity. Additional adhesion-related antigens—filamentous hemagglutinin (FHA), pertactin (PRN) and fimbrial antigens FIM2 and FIM3—broaden coverage against bacterial adhesion and colonization. By antigen composition, the vaccines are commonly grouped as one-component (PT only), two-component (PT plus FHA), three-component (PT, FHA and PRN) and five-component (PT, FHA, PRN, FIM2 and FIM3) products. The review stresses that comparisons should not rest on component number alone, because antigen dose, PT detoxification method, manufacturing process, adjuvant, combination antigens and immunization schedule all differ between products.

The pivotal randomized efficacy trials of acellular vaccines were conducted mainly in the 1990s, and their findings were specific to the products, study designs and case definitions evaluated. A Cochrane review of six efficacy trials involving 46,283 participants reported efficacy of 84–85% for vaccines with three or more components against typical childhood pertussis and 71–78% against mild pertussis. For one- or two-component vaccines, reported efficacy was 59–75% against typical disease and 13–54% against mild disease. These historical estimates depend heavily on the clinical case definition used: the WHO definition for typical pertussis generally required at least 21 days of paroxysmal cough together with laboratory confirmation or an epidemiological link to a confirmed case, while less stringent definitions of mild disease included broader cough criteria that varied across trials. The review cautions that these estimates reflect the products, case definitions and trial conditions included in the review and should not be generalized to every vaccine within a component category.

Protection after vaccination can decline over time, and the review draws on observational evidence and systematic reviews indicating that pertussis vaccine effectiveness wanes after primary vaccination, with faster waning generally reported after acellular schedules than after whole-cell schedules, although estimates vary considerably across studies and settings. One frequently cited figure—that approximately 10% of children might remain protected 8.5 years after vaccination—is explicitly model-based and depends on assumptions about initial vaccine effectiveness. Household-exposure studies from earlier decades provide additional evidence under conditions of intense exposure, including protection following a monocomponent PT toxoid vaccine with estimates varying by dose number, exposure setting and case definition, but these remain historical evidence rather than direct comparisons of current products. Childhood booster studies show that booster vaccination restores antibody responses to PT, FHA, PRN and FIM, though local reactogenicity—particularly injection-site pain, erythema and swelling—is more common after booster doses than after infant primary vaccination.

For adolescents and adults, randomized and non-inferiority studies consistently show that Tdap or dTpa boosters increase antibodies to PT, FHA, PRN and FIM. Comparisons across products generally use immunobridging or non-inferiority designs, with endpoints such as geometric mean concentration, seroresponse rate and fold-rise after booster vaccination. Most Tdap studies meet predefined immunogenicity criteria, supporting their feasibility as boosters. A 2023 German trial found that SIIPL Tdap was non-inferior to Boostrix in healthy people aged 4–65 years. Coverage, however, remains a key challenge: in a French intervention study targeting 25-year-old adults, overall dTcaP vaccine claim within 12 months was only 16.7%, with uptake of 17.4% in the intervention group and 15.5% in the control group and no significant difference between them.

Maternal immunization occupies a particularly consequential place in the review. The purpose of maternal Tdap is to transfer maternal antibodies across the placenta and protect infants before completion of their own primary series, and randomized and follow-up studies show that maternal Tdap increases maternal, cord-blood and early infant antibodies against PT, FHA, PRN or FIM. In several studies, anti-PT geometric mean concentrations at birth were substantially higher in infants born to vaccinated mothers than in controls, and placental transfer was efficient. But the passive protection has a defined time window: an individual participant data meta-analysis of 1,426 mother-infant pairs found that maternally derived antibodies had short half-lives, ranging from 28.7 days for tetanus antibodies to 35.1 days for PRN antibodies, with PT, FHA and FIM2/3 antibodies also decaying on the scale of approximately one month. Maternal Tdap therefore primarily protects infants in the earliest postnatal period, especially before completion of primary immunization.

Timing of vaccination during pregnancy can affect antibody generation and transfer. The Optimum randomized equivalence trial provides evidence on immunogenicity at different gestational ages but does not establish a universally optimal window. In that trial, vaccination between 16 and 32 weeks resulted in equivalent cord-blood anti-PT and anti-PRN IgG concentrations across the studied groups, though anti-FHA IgG concentrations were higher after vaccination at 28–32 weeks than before 24 weeks. No differences in infant antibody concentrations after completion of the primary immunization series were observed between the maternal vaccination-timing groups. The review emphasizes that these findings are based primarily on immunological outcomes and should not be interpreted as demonstrating equivalent clinical protection at every gestational age, and the limited number of preterm infants in the trial prevents firm conclusions about optimal timing for that group.

A more contested issue is blunting—the observation that infants of vaccinated mothers, despite having higher pertussis-specific antibody concentrations at birth and during early infancy, may show lower antibody concentrations after subsequent DTaP, DTwP or pertussis-containing combination vaccines. Because no universally accepted correlate or threshold of protection against pertussis has been established, these lower antibody measurements do not by themselves demonstrate reduced clinical protection. Follow-up studies have reported that differences in selected antibody responses may persist until a later booster, although infants in both groups generally mount strong responses after booster vaccination. The clinical significance of blunting remains uncertain, and current evidence does not establish that it results in increased breakthrough pertussis, hospitalization or severe disease after infant vaccination. Meanwhile, observational evaluations have reported reductions in pertussis cases and hospitalizations among young infants following implementation of maternal vaccination programs, and the review argues that the demonstrated value of maternal vaccination in protecting infants early in life should be weighed against a possible later effect whose clinical importance has not been established.

Safety data across the review are broadly reassuring but nuanced. Common adverse events include injection-site pain, erythema and swelling, as well as transient systemic symptoms such as fever, fatigue, irritability, headache or myalgia, most of which are mild to moderate and resolve within a short period. In a Chinese study of co-purified DTaP booster vaccination at six years of age, vaccine-related adverse events within 28 days occurred in 23.75% of the co-purified DTaP group versus 9.17% in the DT group, with grade ≥3 vaccine-related adverse events in only 0.83% and no vaccine-related serious adverse events or deaths reported. In German adolescents receiving a sixth consecutive dose of an acellular-pertussis-containing vaccine, Tdap was associated with pain in 63.6%, erythema in 51.7% and swelling in 41.4% of participants, while extensive injection-site swelling occurred in 0.94% and all resolved spontaneously. In the SIIPL Tdap trial, solicited local adverse events occurred in 65.5% of participants and systemic events in 46.8%, with grade 3 events in 2.1% and no vaccine-related serious adverse events or deaths.

Maternal safety evidence also supports an acceptable risk-benefit balance, though short-term reactogenicity must be distinguished from pregnancy-outcome signals. A systematic review of pertussis vaccination in pregnancy found an increased risk of chorioamnionitis in a pooled analysis of six observational studies (RR = 1.27, 95% CI: 1.14–1.42), but no significant differences in non-pertussis infections, spontaneous abortion, stillbirth or maternal and neonatal death—an observational signal that does not establish a causal relationship. The review concludes that acellular pertussis vaccines are generally less reactogenic than whole-cell vaccines, that local reactions are common after booster vaccination and have been reported in approximately 40–65% or more of adolescent and adult recipients, and that serious adverse events and deaths have been uncommon in randomized trials. Yet it also warns that the absence of vaccine-related serious adverse events in trials of limited size does not rule out rare risks, and that continued post-marketing surveillance is important—particularly for pregnant women, recipients of combination vaccines, coadministration settings, next-generation vaccines and people with underlying conditions. Future research, the authors argue, should define correlates of protection, evaluate antigen variation, and strengthen evidence on mucosal immunity, coadministration, real-world effectiveness and long-term safety.

Subject of Research: Effectiveness, immunogenicity and safety of acellular pertussis vaccines across diverse populations

Article Title: Acellular pertussis vaccines in diverse populations: a review of effectiveness, immunogenicity, and safety

Article References: Wang, Y., Li, S., Zou, K., Xuan, B., Zhao, M., Yuan, L., & Geng, X. (2026). Acellular pertussis vaccines in diverse populations: a review of effectiveness, immunogenicity, and safety. Frontiers in Microbiology, 17, Article 1981584. https://doi.org/10.3389/fmicb.2026.1981584

Image Credits: AI Generated

DOI: 10.3389/fmicb.2026.1981584

Keywords: acellular pertussis vaccine, DTaP, Tdap, maternal immunization, immunogenicity, vaccine effectiveness, blunting, waning immunity, safety, combination vaccines, pertussis resurgence, nasopharyngeal colonization