Persistence of immune response to HPV-16/18 AS04-adjuvanted cervical cancer vaccine in women aged 15-55 years.

The HPV-16/18 AS04-adjuvanted vaccine (Cervarix®, GlaxoSmithKline Biologicals) has been shown to induce a robust immune response in women aged 15-55 years (103514/NCT00196937). This follow-up study is the first report of persistence of immune response and safety profile through 48 months after vaccination in women aged 15-55 years. In this open-label, age-stratified Phase III study in Germany and Poland (105882/NCT00196937), healthy women aged 15-55 years received 3 doses of HPV-16/18 AS04-adjuvanted vaccine at 0, 1, and 6 months. Anti-HPV-16/18 seropositivity rates and geometric mean antibody titers (GMTs) were assessed by enzyme-linked immunosorbent assay (ELISA) in women aged 15-25 (n=168), 26-45 (n=186) and 46-55 years (n=177) from the time of first vaccination through 48 months. At Month 48, all subjects were seropositive for anti-HPV-16 antibodies and 99.4% were seropositive for anti-HPV-18. Antibody kinetics were as previously reported, with peak response at Month 7 followed by a gradual decline tending towards a plateau in all age groups. Anti-HPV-16/18 GMTs were sustained at Month 48 in all age groups, including women aged 46-55 years in whom GMTs were respectively 11-fold and 5-fold higher than natural infection levels. The vaccine exhibited a clinically acceptable safety profile in all age groups. In summary, the HPV-16/18 AS04-adjuvanted vaccine induces high and sustained immune responses in women aged 15-55 years, with antibody levels remaining several-fold higher than natural infection levels for at least 4 years after the first vaccine dose.

Ten-year immune persistence and safety of the HPV-16/18 AS04-adjuvanted vaccine in females vaccinated at 15-55 years of age.

Women remain at risk of human papillomavirus (HPV) infection for most of their lives. The duration of protection against HPV-16/18 from prophylactic vaccination remains unknown. We investigated the 10-year immune response and long-term safety profile of the HPV-16/18 AS04-adjuvanted vaccine (AS04-HPV-16/18 vaccine) in females aged between 15 and 55 years at first vaccination. Females who received primary vaccination with three doses of AS04-HPV-16/18 vaccine in the primary phase-III study (NCT00196937) were invited to attend annual evaluations for long-term immunogenicity and safety. Anti-HPV-16/18 antibodies in serum and cervico-vaginal secretions (CVS) were measured using enzyme-linked immunosorbent assay (ELISA). Serious adverse events (SAEs) were recorded throughout the follow-up period. Seropositivity rates for anti-HPV-16 remained high (≥96.3%) in all age groups 10 years after first vaccination. It was found that 99.2% of 15-25-year olds remained seropositive for anti-HPV-18 compared to 93.7% and 83.8% of 26-45-year olds and 45-55-year olds, respectively. Geometric mean titers (GMT) remained above natural infection levels in all age groups. Anti-HPV-16 and anti-HPV-18 titers were at least 5.3-fold and 3.1-fold higher than titers observed after natural infection, respectively, and were predicted to persist above natural infection levels for ≥30 years in all age groups. At Year 10, anti-HPV-16/18 antibody titers in subjects aged 15-25 years remained above plateau levels observed in previous studies. Correlation coefficients for antibody titers in serum and CVS were 0.64 (anti-HPV-16) and 0.38 (anti-HPV-18). This study concluded that vaccinated females aged 15-55 years elicited sustained immunogenicity with an acceptable safety profile up to 10 years after primary vaccination, suggesting long-term protection against HPV.

[Economic prerequisites of active influenza prevention]. / Ekonomiczne przeslanki stosowania czynnej profilaktyki grypy.

Influenza and other acute infections of the upper respiratory tract are characterized by a high morbidity and mortality. As a result, they entail not only human but also economic consequences. A typical treatment is nonspecific and conservative. It consists of treatment with nonsteroid antiinflammatory drugs, antitussive drugs, hydratation, etc. Influenza is very often associated with complications especially in high risk groups (children, the elderly, chronically-ill people). The cost of treatment increases because of raising costs of pharmacotherapy and the increased absence from work. Vaccination is a safe and morbidity-diminishing method.

[Adverse reactions after vaccination against influenza in chronically ill people]. / Objawy niepozadane u przewlekle chorych po szczepieniu przeciwko grypie.

The objective was to assess the early and late adverse reactions after vaccination against influenza with the help of SmithKline Beecham's Fluarix vaccine in chronically ill people. 1010 people was selected to undergo vaccination. These included 621 woman aged average 44.2 and 389 men aged average 48.2. The vaccination was conducted simultaneously and the period of monitoring adverse reactions lasted 9 months. The vaccination was done in accordance with recommendations of manufacturer. All the vaccinated people suffered from circulatory system disorders, bone system disorders, mental disorders and endocrinological problems, during the vaccination they were in period of remission. The observed early symptoms fell into two categories: local and general. The late adverse reaction assessed with appearance of aggravation of main chronic disease or with appearance of the new chronic disease. The local symptoms included swelling, reddening and pain in the vaccinated area. 67 people (6.6%) reported swelling, 85 (8.4%) reported reddening, 12 people (1.2%) reported pain in the vaccinated area. The general symptoms included headache, bad mood and temperature over 37.5 degrees C. 19 people (1.9%) reported bad mood, 10 people (1%)--headache and 8 people (0.8%) reported temperature over 37.5 degrees C. Coexistence of two or three types of symptoms was present in 15 cases (1.5%). There were no late adverse reactions in the study group. The low percentage of early adverse reactions and no late adverse reactions encourages a wider use of vaccines against influenza in chronically ill people.

[Early adverse reactions after vaccination against influenza in chronically ill people]. / Wczesne objawy niepozadane obserwowane po szczepieniu przeciwgrypowym zastosowanym u przewlekle chorych.

The objective was to assess the early adverse reactions after vaccination against influenza with the use of Fluarix vaccine (SmithKline Beecham) in chronically ill people. 1010 people were selected to undergo vaccination. The group included 621 women aged on average 44.2 years and 389 men aged on average 48.2. The vaccination was conducted simultaneously and the period of adverse reactions monitoring lasted 14 days. The vaccination was performed in accordance with recommendations of manufacturer. All the vaccinated people suffered from circulatory system disorders, bone system disorders, mental disorders and endocrinological problems. They were in the period of remission during the vaccination. The observed symptoms were classified into two categories: local and general. The local symptoms included swelling, reddening and pain in the vaccinated area. 67 people (6.6%) reported swelling, 85 (8.4%) reported reddening, 12 people (1.2%) reported pain in the vaccinated area. The general symptoms included headache, bad mood and temperature over 37.5 degrees C. 19 people (1.9%) reported bad mood, 10 people (1%)--headache and 8 people (0.8%) reported temperature over 37.5 degrees C. Coexistence of two or three types of symptoms was present in 15 cases (1.5%). The low percentage of early adverse reactions encourages a wider use of vaccines against influenza in chronically ill people.

[Comparison of immunogenicity and safety of Engerix B and Twinrix vaccine]. / Porównanie odpowiedzi immunologicznej oraz bezpieczenstwa stosowania szczepionek Engerix B i Twinrix w profilaktyce wirusowego zapalenia watroby typu B.

The objective of the study was to compare the immunogenicity and the safety profile of Engerix B and Twinrix vaccines. 72 people were qualified for the vaccination, including 41 women (average age 41.2) and 31 men (average age 44.8). The subjects were divided into two groups: Group I--vaccinated with Engerix B (37 persons) and Group II--vaccinated with Twinrix (35 persons). The vaccines were prepared and administered according to the recommended vaccination scheme: 0-1-6 months. 30 days after the last vaccine dose, qualitative and quantitative tests were performed for antibodies anti-HBs (Group I and II) and anti-HAV (Group II). Also, the occurrence of local and general adverse events after vaccinations was observed--on the vaccination day and during 3 consecutive days. In Group I, presence of anti-HBs antibodies was observed in 35 persons, not observed in 2 persons, while in Group II, anti-HBs antibodies were found in 34 persons, while in 1 person no such antibodies were stated. Anti-HAV antibodies were observed in 33 persons from Group II. The anti-HBs antibodies titres did not show significant statistical differences in the groups studied, except for the range 500-1000 IU/l (3 persons in Group I, lack in Group II) and 1000-5000 IU/l (2 persons in Group I, lack in Group II). Local side effects (redness, pain at the injection site, swelling) and general adverse events (fatigue, headache, temperature > 37.5 degrees C) were rare and disappeared within the 4-day observation period. The results achieved are a good recommendation for the vaccines studied, suggesting that vaccination with them are a safe and efficient form of prophylaxis against viral hepatitis.

Persistence of immunity following a booster dose of Haemophilus influenzae type B-Meningococcal serogroup C glycoconjugate vaccine: follow-up of a randomized controlled trial.

BACKGROUND: Antibodies against Haemophilus influenzae type b (Hib) and serogroup C Neisseria meningitidis (MenC) wane after early infant immunization. METHODS: Children previously immunized in a randomized controlled trial at ages 2, 3, and 4 months with DTPa-IPV-Hib and MenC-CRM197 (MenC-CRM group) or DTPa-IPV and Hib-MenC-TT (Hib-MenC-TT group) had blood samples drawn at 1 and 2 years following a booster dose of Hib-MenC-TT at 12 to 15 months of age. A blood sample was also drawn at the year 2 follow-up from a separately recruited age-matched control group who had not received a booster. RESULTS: In 271 children at year 1, mean 14.6 months (range: 12-18 months) following the Hib-MenC-TT booster, MenC bactericidal titers above the protective threshold (rSBA ≥ 1:8) was demonstrated in 89.0% of the Hib-MenC-TT group and 69.5% of MenC-CRM participants. Antipolyribosylribitol phosphate Ig ≥ 1.0 µg/mL (Hib correlate for long-term protection) was seen in 94.9% and 82.5%, respectively.In 379 participants (including 72 control children) at year 2 (age: 39-43 months, 25-31 months post Hib-MenC-TT) persistence of MenC antibodies was demonstrated in 67.1% of the Hib-MenC-TT group and 40.5% of the MenC-CRM group, compared with 44.1% of control group participants. Antipolyribosylribitol phosphate Ig ≥ 1.0 µg/mL was seen in 89.0%, 74.7%, and 38.9%, respectively. CONCLUSIONS: A toddler Hib-MenC-TT booster helps sustain immunity against Hib to 3½ years of age. Persistence of MenC antibody is similar in children primed with MenC-CRM197 in infancy who receive a booster Hib-MenC-TT, to those who receive no booster. Persistence of MenC antibody is better when primed and boosted with Hib-MenC-TT.

Immunogenicity and tolerability of an HPV-16/18 AS04-adjuvanted prophylactic cervical cancer vaccine in women aged 15-55 years.

The immunogenicity and safety of an HPV-16/18 AS04-adjuvanted vaccine were assessed in women aged 26-55 years and compared with women aged 15-25 years in a Phase III, non-randomised, open-label, age-stratified study. Overall the vaccine was well tolerated and 100% seropositivity was achieved 1 month after the third dose in all age groups. There was a high correlation between HPV-16 and HPV-18 antibody levels (IgG) in cervicovaginal secretions and sera, regardless of age. The HPV-16/18 AS04-adjuvanted vaccine induces a robust and persistent immune response in women >26 years of age and generates antibodies that transudate through the cervix epithelium.

Safety and immunogenicity of a DTaP-IPV(Vero) (serum-free) combination vaccine in comparison to DTaP-IPV(Mkc) when administered simultaneously with Haemophilus influenzae type B conjugate vaccine (PRP-T) in children at 2, 3.5, 5 and 16 months of age.

In a phase III, double blind, randomized, noninferiority, multi-centre clinical trial, 817 infants were included and randomly assigned to vaccination with DTaP-IPV(Vero) (N=410) or DTaP-IPV(Mkc) (N=407) vaccines (Statens Serum Institut (SSI), Denmark) in the right thigh. All infants were vaccinated with Act-HIB (Sanofi Pasteur, France) in the left thigh at the same time. The vaccination schedule was 2, 3.5, 5 and 16 months and serum samples were obtained at 6, 16 and 17 months. The primary objective was to demonstrate noninferiority of DTaP-IPV(Vero) to DTaP-IPV(Mkc) as regards immunological protection against polio virus types 1, 2 and 3. Furthermore, the immunogenicity of all vaccine antigens and the safety profile of the vaccines were assessed. The study demonstrated that DTaP-IPV(Vero) was noninferior to DTaP-IPV(Mkc). All antibody concentrations/titres remained at an acceptable level from the end of the primary vaccination series (i.e. 2, 3.5 and 5 months) until the time of the booster vaccination at 16 months. A good booster response was, furthermore, demonstrated for all antigens. No vaccine-related serious adverse events and no injection site granulomas or swelling of the entire thigh occurred. The frequencies of local injection site erythema and swelling as well as systemic adverse events such as fever, irritability, somnolence and decreased appetite were low and acceptable in both treatment groups. In conclusion, DTaP-IPV(Vero) is immunogenic and safe for primary vaccination and for booster vaccination of healthy children.