Sign Out
Pharmacology: Pharmacodynamics: Mechanism of action: VaxigripTetra NH/VaxigripTetra SH provides active immunisation against four influenza virus strains (two A subtypes and two B types) contained in the vaccine.
VaxigripTetra NH/VaxigripTetra SH induces humoral antibodies against the haemagglutinins within 2 to 3 weeks. These antibodies neutralise influenza viruses.
Specific levels of haemagglutination-inhibition (HAI) antibody titre post-vaccination with inactivated influenza virus vaccines have not been correlated with protection from influenza illness but the HAI antibody titres have been used as a measure of vaccine activity. In some human challenge studies, HAI antibody titres of ≥1:40 have been associated with protection from influenza illness in up to 50% of subjects.
Since influenza viruses constantly evolve, the virus strains selected in the vaccine are reviewed annually by the WHO.
Annual revaccination with VaxigripTetra NH/VaxigripTetra SH has not been studied. However, based on clinical experience with the trivalent vaccine, annual influenza vaccination is recommended given the duration of immunity provided by the vaccine and because circulating strains of influenza virus change from year to year.
Efficacy of VaxigripTetra NH/VaxigripTetra SH: Paediatric population: Children from 6 to 35 months of age (active immunisation): A randomized placebo controlled study was conducted in 4 regions (Africa, Asia, Latina America and Europe) over 4 influenza seasons, in more than 5,400 children from 6 to 35 months of age who received two doses (0.5 mL) of VaxigripTetra NH/VaxigripTetra SH (N=2,722), or placebo (N=2,717) 28 days apart to assess VaxigripTetra NH/VaxigripTetra SH efficacy for the prevention of laboratory-confirmed influenza illness caused by any strain A and/or B and caused by vaccine similar strains (as determined by sequencing).
Laboratory-confirmed influenza illness was defined as influenza like-illness (ILI) [occurrence of fever ≥ 38°C (that lasts at least 24 hours) concurrently with at least one of the following symptoms: cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, or diarrhoea], laboratory-confirmed by reverse transcriptase polymerase chain reaction (RT-PCR) and/or viral culture. (See Table 1.)
Click on icon to see table/diagram/imageIn addition, a predefined complementary analysis showed VaxigripTetra NH/VaxigripTetra SH prevented 56.6% (95% CI: 37.0; 70.5) of severe laboratory-confirmed influenza illnesses due to any strain, and 71.7% (95% CI: 43.7; 86.9) of severe laboratory-confirmed influenza illnesses due to vaccine similar strains.
Furthermore, subjects receiving VaxigripTetra NH/VaxigripTetra SH were 59.2% (95% CI: 44.4; 70.4) less likely to experience a medically attended influenza illness than subjects receiving placebo.
Severe laboratory-confirmed influenza illnesses were defined as ILI laboratory-confirmed by RT- PCR and/or viral culture with at least one of the following items: fever > 39.5°C for subjects aged < 24 months or ≥ 39.0°C for subjects aged ≥ 24 months, and/or at least one significant ILI symptom which prevents daily activity (cough, nasal congestion, rhinorrhoea, pharyngitis, otitis, vomiting, diarrhoea), and/or one of the following events: acute otitis media, acute lower respiratory infection (pneumonia, bronchiolitis, bronchitis, croup), inpatient hospitalization.
Children from 3 to 8 years of age (active immunisation): Based on immune responses observed in children from 3 to 8 years of age, the efficacy of VaxigripTetra NH/VaxigripTetra SH in this population is expected to be at least similar to the efficacy observed in children from 6 to 35 months (see Children from 6 to 35 months of age as previously mentioned and Immunogenicity of VaxigripTetra NH/VaxigripTetra SH as follows).
Pregnant women: There are no clinical efficacy data describing use of VaxigripTetra NH/VaxigripTetra SH in pregnant women. However, data are available on Vaxigrip (TIV) and cited as follows, and can be extrapolated to VaxigripTetra NH/VaxigripTetra SH.
In the randomised, controlled, phase IV, clinical studies conducted in Mali, Nepal, and South Africa, approximately 5,000 pregnant women received Vaxigrip (TIV) and approximately 5,000 pregnant women received placebo or control vaccine (quadrivalent meningococcal conjugate vaccine) during the second or third trimester of pregnancy. Vaccine efficacy against laboratory-confirmed influenza in pregnant women was evaluated as a secondary endpoint in all three studies.
The studies conducted in Mali and South Africa demonstrated the efficacy of Vaxigrip for the prevention of influenza in pregnant women (during pregnancy and for approximately 6 months post- delivery), following vaccination during these trimesters of pregnancy.
In the study conducted in Nepal, the efficacy of Vaxigrip (TIV) for the prevention of influenza in pregnant women following vaccination during these trimesters of pregnancy was not demonstrated. (See Table 2.)
Click on icon to see table/diagram/imageInfants younger than 6 months of age born to vaccinated pregnant women (passive protection): Infants younger than 6 months of age are at high risk of influenza, resulting in high rates of hospitalization; however, influenza vaccines are not indicated for use in this age group.
There are no clinical efficacy data in infants born to women vaccinated with VaxigripTetra NH/VaxigripTetra SH during pregnancy; however, efficacy in infants younger than 6 months of age whose mothers received a single 0.5-ml dose of Vaxigrip (TIV) during the second or third trimester has been demonstrated in clinical trials in Nepal, Mali and South Africa and can be extrapolated to VaxigripTetra NH/VaxigripTetra SH. Efficacy of Vaxigrip (TIV) in infants younger than 6 months of age whose mothers were vaccinated during the first trimester has not been studied in these trials. Nevertheless, influenza vaccination during the first trimester should not be postponed (see Use in Pregnancy & Lactation). (See Table 3.)
Click on icon to see table/diagram/imageThe efficacy data indicate a waning of protection in infants born to vaccinated mothers over time after birth.
In the trial conducted in South Africa, vaccine efficacy was highest among infants 8 weeks of age or younger (85.8% [95% CI, 38.3 to 98.4]) and decreased over time; vaccine efficacy was 25.5% (95% CI, -67.9 to 67.8) for infants >8 to 16 weeks of age and 30.4% (95% CI, -154.9 to 82.6) for infants >16 to 24 weeks of age.
In the trial conducted in Mali, there is also a trend of higher efficacy of the trivalent inactivated influenza vaccine in infants during the first 4 months after birth (70.2% [95% CI, 35.7 to 87.6]), with lower efficacy within the fifth month of surveillance (60.7% [95% CI, 33.8 to 77.5]) and a marked fall within the sixth month (37.3% [95% CI, 7.6 to 57.8]).
The prevention of influenza can only be expected if the infants are exposed to the strains included in the vaccine administered to the mother.
Immunogenicity of VaxigripTetra NH/VaxigripTetra SH: Clinical studies performed in adults from 18 to 60 years of age, in elderly over 60 years of age, in children from 3 to 8 years of age and from 6 to 35 months assessed VaxigripTetra NH immune response for HAI Geometric mean antibody titer (GMT) at Day 21 (for adults) and at Day 28 (for children), HAI seroconversion rate (4-fold rise in reciprocal titer or change from undetectable [<10] to a reciprocal titer of ≥40), and HAI GMTR (post-/pre-vaccination titers).
One clinical study performed in adults from 18 to 60 years of age and in children from 9 to 17 years of age described the immune response of VaxigripTetra NH/VaxigripTetra SH for HAI antibody GMT at Day 21. Another clinical study performed in children from 9 to 17 years of age described the immune response of VaxigripTetra NH/VaxigripTetra SH.
One clinical study performed in pregnant women described the immune response of VaxigripTetra NH/VaxigripTetra SH versus Vaxigrip (TIV) for HAI GMT at Day 21, HAI seroconversion rate, and HAI GMTR after one dose administered during the second or third trimester of pregnancy. In this study, the transplacental transfer was evaluated using HAI GMTs of maternal blood, of cord blood and of ratio cord blood/maternal blood, at delivery VaxigripTetra NH/VaxigripTetra SH induced a significant immune response against the 4 influenza strains contained in the vaccine.
Adults and elderly: A total of 832 adults from 18 to 60 years of age and 831 elderly over 60 years of age were assessed in terms of immune response after one dose of VaxigripTetra NH/VaxigripTetra SH.
Immunogenicity results are presented in the tables as follows: See Table 4.
Click on icon to see table/diagram/imagePregnant women and transplacental transfer: In a randomised, controlled clinical study conducted in Finland, a total of 230 pregnant women received VaxigripTetra NH/VaxigripTetra SH and 116 pregnant women received Vaxigrip (TIV) during the second or third trimester of pregnancy (from 20 to 32 weeks of pregnancy).
Immunogenicity results by HAI method, in pregnant women 21 days after vaccination with VaxigripTetra NH/VaxigripTetra SH or Vaxigrip (TIV) are presented in Table 5.
Immunogenicity descriptive assessment by HAI method, at delivery, in blood sample of mother (BL03M), in cord blood sample (BL03B) and of the transplacental transfer (BL03B/ BL03M) are presented in Table 5.
At delivery, the level of antibodies in the cord sample compared to the mother sample was almost doubled for the A/H1N1 strain and increased between 1.5 and 1.7 times for the A/H3N2, B/Brisbane, and B/Phuket strains, supporting that there is transplacental antibody transfer from mother to the newborn, following vaccination of women with VaxigripTetra NH/VaxigripTetra SH or Vaxigrip (TIV) during the second or third trimester of pregnancy.
These data are consistent with the passive protection demonstrated in infants from birth to approximately 6 months of age following vaccination of women during the second or third trimester of pregnancy with Vaxigrip (TIV) in studies conducted in Mali, Nepal, and South Africa. (See Table 5.)
Click on icon to see table/diagram/imagePaediatric population: Children from 9 to 17 years of age: In a total of 429 children from 9 to 17 years of age who received one dose of VaxigripTetra NH/VaxigripTetra SH, the immune response against the 4 strains contained in the vaccine was similar to the immune response induced in adults from 18 to 60 years of age.
Children from 6 months to 8 years of age: A total of 863 children from 3 to 8 years of age received either one or two doses of VaxigripTetra NH/VaxigripTetra SH depending on their previous influenza vaccination history.
Children who received a one- or two-dose schedule of VaxigripTetra NH/VaxigripTetra SH presented a similar immune response following the last dose of each schedule.
In addition to the VaxigripTetra NH/VaxigripTetra SH efficacy, the immunogenicity of two 0.5 mL doses of VaxigripTetra NH/VaxigripTetra SH was assessed 28 days after the last injection of VaxigripTetra NH/VaxigripTetra SH by HAI method in 341 children from 6 to 35 months of age.
Immunogenicity results are presented in the table as follows: See Table 6.
Click on icon to see table/diagram/imageThese immunogenicity data provide supportive information in addition to vaccine efficacy data available in this population (see Efficacy of VaxigripTetra NH/VaxigripTetra SH as previously mentioned).
Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Non-clinical data revealed no special hazard for humans based on conventional studies of repeat dose and local toxicity, reproductive and developmental toxicity and safety pharmacology studies.
