Pertagen

Recombinant pertussis toxin, filamentous haemagglutinin.

Pertagen is a sterile, whitish, turbid and uniform suspension.
Each single dose (0.5 mL) contains Purified Bordetella pertussis antigens: Recombinant Pertussis Toxin (PT_gen) 5 μg, Filamentous Haemagglutinin (FHA) 5 μg.
Pertagen is a recombinant monovalent two-component acellular pertussis vaccine containing two purified Bordetella pertussis antigens (tPT and FHA) which are adsorbed on aluminum hydroxide. Recombinant Pertussis Toxin (tPT) is a genetically-detoxified Pertussis Toxin (PT_gen) obtained by recombinant DNA technology. Pertagen meets the World Health Organization requirements for the manufacture of biological substances and acellular pertussis vaccines.
Excipients/Inactive Ingredients: Aluminum hydroxide, sodium chloride, water for injection.
Formaldehyde may be present as in trace amounts as a manufacturing process residual.

Pharmacology: Immune response: As there is no other monovalent aP vaccine, Pertagen immunogenicity (Table 1) was evaluated in adolescents in a pivotal non-inferiority trial comparing aP_gen and TdaP_gen to a combined Tdap_chem: the pertussis antibody booster response was found significantly higher after one single dose of recombinant pertussis vaccines than after the comparator, demonstrating the non-inferiority and the superiority of the immune response induced by Pertagen, as per WHO TRS 979 and EMA CPMP/EWP/482 guidelines.
In a comparative trial in children (Table 1), Boostagen TdaP_gen containing the same 5 μg PT_gen and FHA as in Pertagen induced a higher anti-PT and similar anti-FHA immune response based on GMC ratio to a pediatric DTaP_chem-IPV containing 25 μg PT_chem and FHA. (See Table 1.)

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Antibody persistence: Immunogenicity studies demonstrated that for pertussis antibodies after an initial Tdap_chem dose, there is a rapid decline during the first year with a gradual decline afterwards (US CDC, 2018).
In a randomized trial (Table 2), Pertagen induced a booster response which persisted during the first year in 90% of vaccinees. The persistence of high neutralizing antibody titers was also shown in 85% adolescents three years after a single booster dose of Pertagen as opposed to 50% vaccinees with Tdap_chem after the first year. (See Table 2.)

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Protection against Pertussis: For pertussis, antibody contributes to protection, but there are no well-established antibody levels which correlate absolutely with protection. However, the rapid decline in antibody levels (after one Tdap dose) is consistent with the vaccine effectiveness data that indicated rapid waning of immunity and a short duration of protection conferred by Tdap containing the chemically inactivated PT (US CDC, 2018).
In a pivotal trial in adolescents (Table 1 and Table 2), pertussis antibody concentrations declined during the first year but the anti-PT antibody levels one, and three years after administration of Pertagen remained significantly higher than after Tdap_chem vaccine which shows that Pertagen may confer higher immunity and longer duration of protection. In a controlled trial in children (Table 1), Boostagen containing the Pertagen aP_gen antigens was also compared to a DTaP-IPV containing the same aP_chem antigens as a DTaP vaccine of which efficacy was documented in a trial.
Maternal vaccination is effective in protecting infants against pertussis infection through both transfer of maternal antibodies and reduced infant exposure to pertussis (ECDC, 2018). Although there is no current correlate of protection to pertussis antigens, induction of anti-PT antibody was shown to induce protection (WHO, 2017).
In a prospective observational study (Table 3), pregnant women were exposed to aP_gen-only, TdaP_gen or Td-only vaccines: pertussis neutralizing antibody titers at delivery were higher in Pertagen and Boostagen groups than in Td vaccinated women. Pertagen induced a higher anti-PT response than Boostagen. Vaccination with Pertagen in the 2^nd trimester of pregnancy also induced higher anti-PT concentration than when given in the 3^rd trimester.
Boostagen was also compared to Tdap_chem in two randomized trials in women: no difference in pertussis immune response was found after one Boostagen dose between women of childbearing age and pregnant women nor when vaccine was given in pregnant women either during the 2^nd or 3^rd trimester of gestation. The pooled data in pregnant and non-pregnant women shows that Boostagen induced a higher anti-PT response at Day 28 after vaccination based on the adjusted GMC ratio of Boostagen to comparator (2.6 (98.75% CI 2.0-3.5)). Boostagen was non-inferior to comparator based on the lower limit of the 98.75% CI of the adjusted GMC ratio (>0.5 different margin). It is also above 1 different margin and hence, was considered superior.
These results indicate more effective maternal immune response and antibody transfer from mother to infant after maternal vaccination with Pertagen and Boostagen than with chemically inactivated PT (PT_chem) containing vaccine. (See Table 3.)

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Pertagen is indicated for active booster immunization against pertussis in individuals from the age of 3 years onwards.
Pertagen is indicated for passive protection against pertussis in early infancy following maternal immunization during pregnancy.
Pertagen should be used in accordance with official recommendations for booster and catch up vaccination and maternal immunization against pertussis only.

Posology: A single 0.5 mL dose of Pertagen is recommended.
Pertagen may be given in individuals aged 3 years and onwards requiring protection against pertussis only as booster, catch-up or maternal immunization in accordance with national, WHO, US or EU official recommendations or medical practices, including: pregnant women in the second or third trimester and preferably at least 15 days before the end of pregnancy to prevent pertussis in mothers and in infants too young to be vaccinated; multiparous women with closely spaced pregnancies to avoid "over-vaccination" and hypersensitivity reactions due to repeated injections of Tdap-IPV or Tdap vaccines; adolescents, adults, household contacts, childcare providers to maintain herd immunity and to protect the youngest infants; healthcare providers to prevent nosocomial transmission to infants.
Pertagen may be considered as an alternative to acellular pertussis combinations (DTaP or Tdap-based vaccines) for pertussis booster immunization in subjects with known hypersensitivity to tetanus (Arthus-type hypersensitivity reaction) or diphtheria vaccines and in individuals who have received multiple and frequent tetanus or diphtheria vaccine doses.
Administration: Pertagen should be administered by deep intramuscular injection, preferably in the deltoid region. The skin over the site of injection should be cleaned before injection. Shake well before use. Do not use if resuspension does not occur after vigorous-shaking. Open the needle cap of the pre-filled syringe, administer the total volume of 0.5 mL intramuscularly (IM).

No case of overdose was reported with Pertagen.

Pertagen should not be administered to individuals with past experience or signs of: severe allergic reaction or any encephalopathy with unknown origin following administration of pertussis vaccines or to any-components of the vaccine; neurological disorders, uncontrolled epilepsy or progressive encephalopathy.
Hypersensitivity, thrombocytopenia or neurological complications following an earlier immunization against diphtheria and/or tetanus are not contraindication to the use of Pertagen.

In compliance with local requirements, vaccination should be preceded by a review of the medical history and a clinical examination. As with all injectable vaccines, appropriate medical care should be readily available in case of a rare anaphylactic reaction after vaccination.
In the case of acute severe febrile illness, immunosuppressive treatment or immunodeficiency, vaccination should be postponed. Nevertheless, vaccination should be considered in HIV-infected persons or those with chronic immunodeficiency disorder.
As with any vaccines, Pertagen should be administered with caution to subjects who had high body temperature (≤40°C) without any identifiable causes within 48 hours after a previous immunization with any pertussis vaccines. Pertagen should be given with caution in individuals receiving anticoagulant therapy or those with thrombocytopenia or any coagulation disorder because bleeding at injection site may occur after intramuscular injection.

Pregnancy: Because of the potential benefits of maternal pertussis immunization and the lack of monovalent acellular pertussis vaccine in the USA, pregnant women should receive Tdap boosters during each pregnancy even though moderate to severe local reactions have been associated with high levels of tetanus and diphtheria antitoxin (WHO, 2014).
In a randomized controlled trial where 80 pregnant women were exposed to Boostagen TdaP_gen (Td vaccine combined to Pertagen aP_gen components) have shown a safety profile in mothers and foetus/newborns similar to the chemically-detoxified pertussis toxoid (Tdap_chem) comparator vaccine. In addition, safety data from active post-marketing surveillance (including a prospective observational study) where 1,778 pregnant women were exposed to Pertagen or Boostagen in the second or third trimester of pregnancy have shown no vaccine-related adverse effect on pregnancy or the health of newborns.
No adverse effects on pregnancy, parturition, lactation or prenatal and postnatal development were observed in two reproductive and developmental animal toxicity studies evaluating Pertagen antigens combined to tetanus and diphtheria toxoids.
Lactation: No study on lactation was performed in humans. However, as Pertagen contains inactivated antigens, no risk to the breastfed infant should be expected.

Summary of the safety profile: As there is no other-monovalent pertussis vaccine available, Pertagen monovalent 2-component aP_gen and vaccines containing Pertagen components (TdaP_gen and DTaP_gen) were compared to 2, 3 or 5-components acellular pertussis-based vaccines (Tdap_chem and DTaP_chem).
The safety profile of Pertagen or vaccines containing Pertagen components (in quantity not less than in Pertagen) is based on the data from six randomized controlled trials in children, adolescents and adults including pregnant women (Table 4). Within 7 days after vaccination, the most common events occurring were local injection site pain (pain, redness and induration) and systemic reactions (headache, fatigue, myalgia, malaise and arthralgia).
The frequency, severity and duration of adverse events were similar in subjects vaccinated either with aP_gen-based vaccines or aP_chem-based comparator vaccines. These signs and symptoms were mostly mild and moderate in intensity and resolved without sequelae within a few days. (See Table 4.)

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Data from active pharmacovigilance of Pertagen (aP_gen) and Boostagen (TdaP_gen) also confirmed the safety profile of Pertagen in 11,429 individuals aged 11 years and above including 437 adolescents, 10,960 adults (including 1,778 pregnant women) and 32 elderly aged 65 years and above.

Interaction studies with other drugs have not been investigated. However, since Pertagen is an inactivated vaccine, the simultaneous administration of Pertagen with other vaccines at separate site of injections is unlikely to cause any interference with the immune response.

Pertagen should be stored at 2°C to 8°C. Do not freeze. Discard if vaccine has been frozen.
Shelf-Life: 3 years.

Vaccines, Antisera & Immunologicals

J07AJ02 - pertussis, purified antigen ; Belongs to the class of pertussis bacterial vaccines.

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