Maternal Immunization With Tetanus Toxoid, Reduced Diphtheria Toxoid, Reduced-dose (2 µg) Recombinant Pertussis Vaccine (TdaP2gen) and Its Effect on the Immune Response in Thai Infants up to 15-18 Months Old (M-PRIME)

Maternal Immunization With Tetanus Toxoid, Reduced Diphtheria Toxoid, Reduced-dose (2 µg) Recombinant Pertussis Vaccine (TdaP2gen) and Its Effect on the Immune Response to Tetanus, Diphtheria and Pertussis in Thai Infants up to 15-18 Months Old: An Open-label, Randomized Controlled Trial

Pertussis remains a major global public health problem. In Thailand, pertussis vaccination is recommended during pregnancy at 20-32 weeks' gestation, together with routine childhood diphtheria-tetanus-pertussis vaccination administered as a primary series at 2, 4, and 6 months and booster doses at 18 months and 4-6 years of age.

TdaP2gen, a newly developed combined tetanus, diphtheria, and recombinant genetically detoxified acellular pertussis vaccine containing 2 µg pertussis antigen, has shown favorable safety and non-inferior immunogenicity compared with existing pertussis vaccines. However, data on its use in pregnant women, transplacental antibody transfer, and potential immune interference in infants remain limited.

This study aims to evaluate the safety and immunogenicity of TdaP2gen in pregnant women, assess antibody transfer to newborns, and investigate immune responses to tetanus, diphtheria, and pertussis following primary and booster pertussis-containing vaccinations in infants and toddlers, including comparisons between whole-cell and acellular pertussis-containing vaccine schedules.

Study Overview

• Status: Not yet recruiting
• Conditions: Pertussis; Tetanus; Diphtheria; Vaccine-Preventable Diseases
• Intervention / Treatment: Biological: Maternal TdaP2gen vaccine; Biological: Infant Acellular Pertussis-containing Vaccine; Biological: Infant Whole-cell Pertussis-containing Vaccine

Detailed Description

Pertussis remains a major global public health problem. In Thailand, pertussis vaccination is recommended for all pregnant women at 20-32 weeks' gestation to protect newborns and young infants against pertussis during early life. In addition, combined diphtheria-tetanus-pertussis vaccination is routinely administered as a primary series at 2, 4, and 6 months of age, followed by booster doses at 18 months and 4-6 years of age.

TdaP2gen is a combined tetanus, diphtheria, and recombinant genetically detoxified acellular pertussis vaccine, containing 2 µg pertussis antigen, which has been recently developed. Previous clinical studies have demonstrated that TdaP2gen is safe and elicits non-inferior immune responses against pertussis compared with the 5 µg recombinant acellular pertussis vaccine (TdaP5gen) and the chemically inactivated Tdap vaccine. However, as TdaP2gen is a newly licensed vaccine in Thailand, data on its safety, immunogenicity in pregnant women, placental antibody transfer to infants, and potential immune interference with infant responses to routine pertussis-containing vaccines remain limited.

Therefore, this study aims to evaluate the safety and immunogenicity of TdaP2gen in pregnant women, assess transplacental antibody transfer to newborns, and investigate its impact on immune responses to diphtheria, tetanus, and pertussis following primary series and booster vaccination up to 15-18 months of age in infants and young children.

This study is divided into 3 phases as follows:

Phase 1 - Maternal and fetal phase: This phase will evaluate the immunogenicity and safety of TdaP2gen vaccination in pregnant women, including immune responses against tetanus, diphtheria, and pertussis, as well as the transplacental transfer of antibodies to newborns.

Phase 2 - Infant phase: This phase will assess immune responses to tetanus, diphtheria, and pertussis in infants following completion of the primary pertussis-containing vaccine series at 2, 4, and 6 months of age, comparing infants who receive whole-cell pertussis-containing vaccines (wP-containing vaccines) with those who receive acellular pertussis-containing vaccines (aP-containing vaccines).

Phase 3 - Toddler phase: This phase will evaluate immune responses to tetanus, diphtheria, and pertussis in toddlers after receiving a pertussis-containing booster vaccination at 15-18 months of age, comparing children who receive whole-cell pertussis-containing vaccines (wP-containing vaccines) with those who receive acellular pertussis-containing vaccines (aP-containing vaccines).

• Study Type: Interventional
• Enrollment (Estimated): 320
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tavitiya Sudjaritruk, MD, PhD; Phone Number: +66-53-936471; Email: tavitiya.s@cmu.ac.th

Study Locations

• Thailand
  • Chiang Mai, Thailand, 50200
    • Department of Pediatrics, Faculty of Medicine, Chiang Mai University
    • Contact: Tavitiya Sudjaritruk, MD, PhD; Phone Number: +66-53-93-6471; Email: tavitiya.s@cmu.ac.th

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: Yes

Description

Phase 1: Pregnant women

Inclusion Criteria:

• Pregnant women aged 20 to 45 years
• Healthy women in good general health
• Gestational age between 20 and 32 weeks at enrollment
• Singleton pregnancy
• Low-risk, uncomplicated pregnancy as assessed by an obstetrician
• No evidence of congenital anomalies identified on prenatal ultrasonographic screening
• Willing to receive TdaP2gen vaccination and comply with collection of biological specimens as specified in the study protocol
• Willing to allow their infant to receive either whole-cell pertussis-containing or acellular pertussis-containing combination vaccines according to the study randomization process, and to allow collection of biological specimens from the infant as specified in the study protocol
• Able and willing to provide written informed consent prior to study participation

Exclusion Criteria:

• Receipt of a tetanus-, diphtheria-, and chemical-detoxified pertussis-containing vaccine within 1 year prior to enrollment, or receipt of a tetanus-, diphtheria-, and genetic-detoxified pertussis-containing vaccine (TdaPgen) or genetic-detoxified acellular pertussis vaccine (aPgen) within 2 years prior to enrollment, including during the current pregnancy
• History of laboratory-confirmed or clinically diagnosed pertussis infection within 1 year prior to enrollment
• Presence of underlying medical conditions that may affect study outcomes, including but not limited to malignancy, autoimmune disease, immunodeficiency, epilepsy, hypertension, renal disease, or liver disease, as determined by the investigators
• Pregnancy complications including hypertension (blood pressure >140/90 mmHg with proteinuria, or >150/100 mmHg regardless of proteinuria), current antihypertensive treatment, or preeclampsia
• Endocrine disorders including hyperthyroidism, untreated hypothyroidism, or impaired glucose tolerance (e.g., type 1 or type 2 diabetes mellitus) diagnosed before or during pregnancy requiring treatment beyond dietary control
• Severe or progressive neurological disorders, including epilepsy or a history of Guillain-Barré syndrome
• Receipt of immunosuppressive agents, immunomodulatory agents, or high-dose systemic corticosteroids (>2 mg/kg/day, >20 mg/day, or equivalent) for more than 14 consecutive days within 6 months prior to enrollment
• History of stillbirth, neonatal death, or recurrent spontaneous abortion (≥3 episodes).
• Current medical or surgical treatment for prevention of preterm labor during the current pregnancy
• Receipt of blood products, blood components, or immunoglobulins within 6 months prior to enrollment
• Receipt of live attenuated vaccines within 3 months or any other vaccines within 28 days prior to enrollment
• History of hypersensitivity or adverse reactions to study vaccines or vaccine components, or history of severe allergic reactions such as anaphylaxis to any vaccine
• Behavioral, cognitive, or psychiatric conditions that, in the opinion of the investigator, may interfere with study participation or protocol compliance
• History of smoking, alcohol abuse, or intravenous drug use that, in the opinion of the investigator, may interfere with study assessments or outcomes
• Fever (body temperature ≥38.0°C or equivalent) within 72 hours prior to enrollment
• Acute illness within 4 weeks prior to enrollment
• Contraindications to intramuscular vaccination, including thrombocytopenia, coagulation disorders, hemophilia A or B, or use of anticoagulant therapy during pregnancy
• Concurrent participation in another clinical study involving investigational vaccines or medications during participation in this study
• Any medical or obstetric condition that, in the opinion of the study investigator, may interfere with study assessments or increase the risk to the mother or infant associated with study participation

Phase 2: Infants

Inclusion Criteria:

- All infants born to pregnant women enrolled in Phase 1 who received TdaP2gen vaccination during pregnancy will be eligible for enrollment to Phase 2 study

Exclusion Criteria:

• Gestational age <32 weeks (very preterm birth)
• Birth weight <1,500 grams (very low birth weight)
• Presence of major congenital anomalies identified after birth, including congenital abnormalities associated with genetic disorders, congenital infections, or severe structural abnormalities involving major organ systems such as the central nervous system, cardiovascular system, respiratory system, hepatobiliary and gastrointestinal system, or genitourinary system
• Presence of severe neonatal medical conditions that may affect immune responses to study vaccines, including but not limited to severe respiratory distress, severe bronchopulmonary dysplasia, hypoxic ischemic encephalopathy (HIE), severe intraventricular hemorrhage (IVH), severe sepsis, non-physiologic jaundice, neonatal autoimmune thrombocytopenia, neurological disorders such as neonatal convulsions, necrotizing enterocolitis, or intracranial hemorrhage
• Presence of conditions associated with increased risk of serious adverse reactions to study vaccines
• Any medical condition or circumstance that, in the opinion of the study investigator, may interfere with study assessments or increase the risk to the participant associated with study participation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: Maternal TdaP2gen Group; Maternal TdaP2gen Group	Biological: Maternal TdaP2gen vaccine; A combined tetanus toxoid, reduced diphtheria toxoid, reduced-dose (2 µg) genetically-detoxified recombinant acellular pertussis vaccine (TdaP2gen)
Experimental: Phase 2: Infant Acellular Pertussis-containing Vaccine Group; Infant Acellular Pertussis-containing Vaccine Group	Biological: Infant Acellular Pertussis-containing Vaccine; An infant acellular pertussis (aP)-containing vaccine
Active Comparator: Phase 2: Infant Whole-cell Pertussis-containing Vaccine Group; Infant Whole-cell Pertussis-containing Vaccine Group	Biological: Infant Whole-cell Pertussis-containing Vaccine; An infant whole-cell pertussis (wP)-containing vaccine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Maternal anti-pertussis toxin (PT), anti-filamentous hemagglutinin (FHA), anti-diphtheria toxoid, and anti-tetanus toxoid immunoglobulin G (IgG) geometric mean concentrations and seroresponse rates following TdaP2gen vaccination during pregnancy	Assessment of maternal anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates before TdaP2gen vaccination, after vaccination, and at delivery	Pre-vaccination baseline, 4 weeks after vaccination (+/- 14 days), and at delivery
Phase 1: Cord blood anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates at birth	Assessment of anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates in cord blood collected at delivery among infants born to TdaP2gen vaccinated mothers	At delivery
Phase 1: Incidence of solicited local and systemic adverse events, serious adverse events, and adverse pregnancy outcomes of TdaP2gen vaccination during pregnancy	Assessment of solicited local and systemic adverse events as well as serious adverse events and adverse pregnancy outcomes among pregnant women receiving TdaP2gen vaccination during pregnancy.	From vaccination until delivery, assessed up to approximately 22 weeks post-vaccination.
Phase 2: Infant anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates following primary diphtheria-tetanus-pertussis vaccination series	Assessment and comparison of anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates between infants born to mothers receiving TdaP2gen vaccine during pregnancy who are randomized to receive either aP- or wP-containing vaccines as the primary vaccination series during infancy	Pre-primary series vaccination (within 2 months after birth) and post-primary series vaccination (at age 7 months +/- 14 days)
Phase 3: Infant anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates following booster diphtheria-tetanus-pertussis vaccination	Assessment and comparison of anti-PT, anti-FHA, anti-diphtheria toxoid, and anti-tetanus toxoid IgG geometric mean concentrations and seroresponse rates between infants born to mothers receiving TdaP2gen vaccine during pregnancy who previously received either aP or wP-containing vaccines during the primary vaccination series and subsequently receive booster vaccination at 15-18 months of age	At 12 months of age (+/- 14 days), pre-booster vaccination, and 1 month after booster vaccination (+/- 14 days)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Maternal pertussis-neutralizing antibody geometric mean titers following TdaP2gen vaccination during pregnancy	Assessment of maternal pertussis-neutralizing antibody geometric mean titers in a subset of 40 pregnant women before TdaP2gen vaccination, after vaccination, and at delivery	Pre-vaccination baseline, 4 weeks after vaccination (+/- 14 days), and at delivery
Phase 1: Cord blood pertussis-neutralizing antibody geometric mean titers at birth	Assessment of pertussis-neutralizing antibody geometric mean titers in cord blood samples from newborns of a subset of 40 vaccinated pregnant women at delivery	At delivery
Phase 1: Knowledge and acceptability of pertussis and pertussis vaccine among pregnant women assessed using a structured questionnaire	Assessment of knowledge and acceptability of pertussis and pertussis vaccine among pregnant women using a structured questionnaire	Pre-vaccination baseline
Phase 2: Infant pertussis-neutralizing antibody geometric mean titers following primary diphtheria-tetanus-pertussis vaccination series	Assessment and comparison of pertussis-neutralizing antibody geometric mean titers in a subset of 40 infants born to mothers receiving TdaP2gen vaccine during pregnancy who are randomized to receive either aP- or wP-containing vaccines as the primary vaccination series during infancy	Pre-primary series vaccination (within 2 months after birth) and post-primary series vaccination (at age 7 months +/- 14 days)
Phase 2: Incidence of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following the primary diphtheria-tetanus-pertussis vaccination series in infants	Assessment and comparison of the frequency and severity of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following administration of aP- or wP-containing vaccines during the primary vaccination series in infants born to mothers receiving TdaP2gen vaccine during pregnancy	From the first dose of the primary diphtheria-tetanus-pertussis vaccination series until 1 month after completion of the primary vaccination series, assessed up to approximately 5 months
Phase 3: Infant pertussis-neutralizing antibody geometric mean titers following booster diphtheria-tetanus-pertussis vaccination	Assessment and comparison of pertussis-neutralizing antibody geometric mean titers in a subset of 40 infants born to mothers receiving TdaP2gen vaccine during pregnancy who previously received either aP or wP-containing vaccines during the primary vaccination series and subsequently receive booster vaccination at 15-18 months of age	At 12 months of age (+/- 14 days), pre-booster vaccination, and 1 month after booster vaccination (+/- 14 days)
Phase 3: Incidence of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following booster diphtheria-tetanus-pertussis vaccination in infants	Assessment and comparison of the frequency and severity of solicited local and systemic adverse events, unsolicited adverse events, and serious adverse events following administration of aP or wP booster vaccination in infants born to mothers receiving TdaP2gen vaccine during pregnancy	From booster vaccination through 28 days after vaccination

Collaborators and Investigators

• Sponsor: Chiang Mai University
• Collaborators: Thailand Center of Excellence for Life Sciences
• Investigators: Principal Investigator: Tavitiya Sudjaritruk, MD, PhD, Department of Pediatrics, Faculty of Medicine, Chiang Mai University

Publications and helpful links

General Publications

• Chokephaibulkit K, Puthanakit T, Chaithongwongwatthana S, Bhat N, Tang Y, Anugulruengkitt S, Chayachinda C, Anuwutnavin S, Lapphra K, Rungmaitree S, Tawan M, Andi-Lolo I, Holt R, Fortuna L, Kerdsomboon C, Yuwaree V, Mansouri S, Thai PH, Innis BL. Effective and safe transfer of maternal antibodies persisting two months postpartum following maternal immunization with different doses of recombinant pertussis-containing vaccines. Vaccine. 2024 Jan 12;42(2):383-395. doi: 10.1016/j.vaccine.2023.11.042. Epub 2023 Dec 7.
• Puthanakit T, Chokephaibulkit K, Anugulruengkitt S, Chaithongwongwatthana S, Phongsamart W, Wittawatmongkol O, Rungmaitree S, Tang Y, Kerdsomboon C, Yuwaree V, Fortuna L, Mansouri S, Pham HT, Bhat N, Innis BL. Infant Responses to Primary Immunization Following Vaccination in Pregnancy With Varying Doses of Recombinant Acellular Pertussis Vaccine Alone or Combined With Tetanus-Diphtheria. Pediatr Infect Dis J. 2025 Feb 1;44(2S):S56-S60. doi: 10.1097/INF.0000000000004609. Epub 2025 Feb 14.

Study record dates

Study Major Dates

• Study Start (Estimated): May 26, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: May 20, 2026
• First Submitted That Met QC Criteria: May 27, 2026
• First Posted (Actual): June 2, 2026

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: May 27, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Safety; Immunogenicity; Newborns; Pregnant women; Immune interference; Infants and young children; Pertussis-containing vaccine; Genetically-detoxified recombinant acellular pertussis vaccine
• Additional Relevant MeSH Terms: Respiratory Tract Infections; Infections; Respiratory Tract Diseases; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Negative Bacterial Infections; Actinomycetales Infections; Clostridium Infections; Corynebacterium Infections; Bordetella Infections; Vaccine-Preventable Diseases; Diphtheria; Tetanus; Whooping Cough
• Other Study ID Numbers: PED-2569-0103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is not a plan to make individual participant data (IPD) available for this study.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No