Pharmacological properties : תכונות פרמקולוגיות

Pharmacodynamic Properties

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: Bacterial vaccines, pertussis vaccines, ATC code: J07AJ52 
Immune response

Approximately one month following booster vaccination with Boostrix, the following seroprotection / seropositivity rates were observed (Table 3).

Table 3: Immune response in children, adolescents and adults
Adults and
Children from adolescents from the age of 4 the age of 10 years onwards
Antigen                   Response(1)          years onwards
ATP(2)
ATP(2)
N=415
N=1694
(% vaccinees)
(% vaccinees)
Diphtheria                           ≥ 0.1 IU/ml                   97.2%                   99.8% Tetanus                              ≥ 0.1 IU/ml                   99.0%                  100.0% Pertussis:
- Pertussis toxoid                                                 97.8%                   99.0% - Filamentous haemagglutinin         ≥ 5 EL.U/ml                   99.9%                  100.0% - Pertactin                                                        99.4%                   99.8% (1)
Response: where, at the specified time point, a concentration of antibodies against diphtheria and tetanus ≥ 0.1 IU/ml was considered as seroprotection and a concentration of antibodies against pertussis ≥ 5 EL.U/ml was considered as seropositivity.
(2)
ATP: According to protocol – includes all eligible subjects, who had received a single booster dose of Boostrix, for whom immunogenicity data was available for at least one antigen at the specified time-point.
N: the minimum number of subjects with available data for each antigen 
In adolescents and adults, comparative trials have demonstrated that one month post-vaccination, diphtheria antibody titres are similar to adult-type Td vaccines with the same antigen content as Boostrix; lower tetanus antibody titres were seen as compared to adult-type Td vaccines.

As with other adult-type Td vaccines, Boostrix induces higher titres of both anti-D and anti-T antibodies in children and adolescents as compared to adults.

Persistence of the immune response

Three to 3.5 years, 5 to 6 years and 10 years following a first vaccination with Boostrix, the following seroprotection/seropositivity rates were observed in subjects vaccinated according to protocol (ATP1) (Table 4).


Table 4: Persistence of immune response in children, adolescents and adults 
Children from the age
Antigen           Response(2)       Adults and adolescents from the age of 10 years onwards of 4 years onwards
(% vaccinees)
(% vaccinees)
5 to 6
3-3.5 years                                   10 years          3-3.5 years 5 years persistence                                          years persistence                                  persistence        persistence persistence
Adult(3)    Adole-     Adult(3)    Adole-     Adult(3)   Adole- scent(3)               scent(3)              scent(3)    (N=118)       (N=68) (N=309)    (N=261)     (N=232)    (N=250)     (N=158)    (N=74)
Diphtheria           ≥ 0.1 IU/ml        71.2%       91.6%      84.1%       86.8%      64.6%       82.4%      97.5 %        94.2 % Not
≥ 0.016 IU/ml(4)   97.4%       100%       94.4%       99.2%      89.9%      98.6%        100 % determined
Tetanus              ≥ 0.1 IU/ml        94.8%       100%       96.2%       100%       95.0%      97.3%       98.4 %        98.5 % Pertussis
Pertussis toxoid                      90.6%       81.6%      89.5%       76.8%      85.6%      61.3%       58.7 %        51.5 % Filamentous        ≥ 5 EL.U/ml haemagglutinin                        100%        100%       100%        100%       99.4%      100%        100 %         100 % Pertactin                            94.8%       99.2%      95.0%       98.1%      95.0%      96.0%       99.2 %        100 % (1)
ATP: According to protocol – includes all eligible subjects, who had received a single booster dose of Boostrix, for whom immunogenicity data was available for at least one antigen at the specified time-point.
(2)
Response: Where, at the specified time point, a concentration of antibodies against diphtheria and tetanus ≥ 0.1 IU/ml was considered as seroprotection and a concentration of antibodies against pertussis ≥ 5 EL.U/ml was considered as seropositivity.
(3)
The terms ‘adult’ and ‘adolescent’ reflect the ages at which subjects received their first vaccination with Boostrix.
(4)
Percentage of subjects with antibody concentrations associated with protection against disease (≥ 0.1 IU/ml by ELISA assay or ≥ 0.016 IU/ml by an in-vitro Vero-cell neutralisation assay).
N = the minimum number of subjects with available data for each antigen 
Efficacy in protecting against pertussis

The pertussis antigens contained in Boostrix are an integral part of the paediatric acellular pertussis combination vaccine (Infanrix), for which efficacy after primary vaccination has been demonstrated in a household contact efficacy study. The antibody titres to all three pertussis components following vaccination with Boostrix are higher than those observed during the household contact efficacy trial. Based on these comparisons, Boostrix would provide protection against pertussis, however the degree and duration of protection afforded by the vaccine are undetermined.

Passive protection against pertussis in infants (below 3 months of age) born to mothers vaccinated during pregnancy

In a randomised, cross-over, placebo-controlled study, higher pertussis antibody concentrations were demonstrated at delivery in the cord blood of babies born to mothers vaccinated with Boostrix (dTpa group; N=291) versus placebo (control group; N=292) at 27-36 weeks of pregnancy. The cord blood geometric mean concentrations of antibodies against the pertussis antigens PT, FHA and PRN were 46.9, 366.1 and 301.8 IU/ml in the dTpa group, and 5.5, 22.7 and 14.6 IU/ml in the control group. This corresponds to antibody titres that are 8, 16 and 21 times higher in the cord blood of babies born to vaccinated mothers versus controls. These antibody titres may provide passive protection against pertussis as shown by observational effectiveness studies.

Immunogenicity in infants and toddlers born to mothers vaccinated during pregnancy The immunogenicity of Infanrix hexa (diphtheria, tetanus, pertussis, hepatitis B, inactivated poliovirus, Haemophilus influenzae type b conjugate vaccine) in infants and toddlers born to healthy mothers vaccinated with Boostrix at 27-36 weeks of pregnancy was evaluated in two clinical studies.

Infanrix hexa was co-administered with a 13-valent pneumococcal conjugate vaccine to infants for primary vaccination (n=268); and to the same infants/toddlers from 11 to 18 months as booster dose (n=229).

Post-primary and post-booster vaccination, immunological data did not show clinically relevant interference of maternal vaccination with Boostrix on the infant’s and toddler’s responses to diphtheria, tetanus, hepatitis B, inactivated poliovirus, Haemophilus influenzae type b or pneumococcal antigens.

Lower antibody concentrations against pertussis antigens post-primary (PT, FHA and PRN) and post-booster (PT, FHA) vaccination were observed in infants and toddlers born to mothers vaccinated with Boostrix during pregnancy. The fold-increases of anti-pertussis antibody concentrations from the pre-booster to the 1-month post-booster time point were in the same range for infants and toddlers born to mothers vaccinated with Boostrix or with placebo, demonstrating effective priming of the immune system. In the absence of correlates of protection for pertussis, the clinical relevance of these observations remains to be fully understood.
However, current epidemiological data on pertussis disease following the implementation of dTpa maternal immunisation do not suggest any clinical relevance of this immune interference.


Effectiveness in the protection against pertussis disease in infants born to women vaccinated during pregnancy

Boostrix or Boostrix-Polio vaccine effectiveness (VE) was evaluated in three observational studies, in UK, Spain and Australia. The vaccine was used during the third trimester of pregnancy to protect infants below 3 months of age against pertussis disease, as part of a maternal vaccination programme.

Details of each study design and results are provided in Table 5.
Table 5: VE against pertussis disease for infants below 3 months of age born to mothers vaccinated during the third trimester of pregnancy with Boostrix/Boostrix-Polio: 
Study location           Vaccine      Study design             Vaccination Effectiveness UK                       Boostrix-    Retrospective,             88% (95% CI: 79, 93) Polio     screening method
Spain                    Boostrix Prospective, matched         90.9% (95% CI: 56.6, 98.1) case-control
Australia                Boostrix Prospective, matched            69% (95% CI: 13, 89) case-control
CI: confidence interval

If maternal vaccination occurs within two weeks before delivery, vaccine effectiveness in the infant may be lower than the figures in the table.

Immune response after a repeat dose of Boostrix

The immunogenicity of Boostrix, administered 10 years after a previous booster dose with reduced-antigen content diphtheria, tetanus and acellular pertussis vaccine(s) has been evaluated.
One month post vaccination, > 99 % of subjects were seroprotected against diphtheria and tetanus and seropositive against pertussis.

Immune response in subjects without prior or with unknown vaccination history 
After administration of one dose of Boostrix to 83 adolescents aged from 11 to 18 years, without previous pertussis vaccination and no vaccination against diphtheria and tetanus in the previous 5 years, all subjects were seroprotected against tetanus and diphtheria. The seropositivity rate after one dose varied between 87% and 100% for the different pertussis antigens.

After administration of one dose of Boostrix to 139 adults ≥ 40 years of age that had not received any diphtheria and tetanus containing vaccine in the past 20 years, more than 98.5% of adults were seropositive for all three pertussis antigens and 81.5% and 93.4% were seroprotected against diphtheria and tetanus respectively. After administration of two additional doses one and six months after the first dose, the seropositivity rate was 100% for all three pertussis antigens and the seroprotection rates for diphtheria and tetanus reached 99.3% and 100% respectively.

Immune response and safety profile in subjects on active treatment for obstructive airway diseases
The safety and immunogenicity of Boostrix have been evaluated in a descriptive meta-analysis study combining data from 222 subjects ≥ 18 years of age vaccinated with Boostrix while on active treatment for obstructive airway disease such as asthma or Chronic Obstructive Pulmonary Disease (COPD). One month after Boostrix vaccination, the immune responses against diphtheria and tetanus antigens in terms of seroprotective rates (≥ 0.1 IU/mL) were respectively 89.0% and 97.2%, and against pertussis in terms of booster responses these were 78.3 %, 96.1 % and 92.2 % against pertussis toxoid [PT], filamentous haemagglutinin [FHA] and pertactin [PRN], respectively. These results are consistent with the responses obtained in the general adult population and with a similar safety profile.

Pharmacokinetic Properties

5.2    Pharmacokinetic properties
Evaluation of pharmacokinetic properties is not required for vaccines.