A phase III randomized, controlled study to assess and compare the immunogenicity and tolerability of single and multi-dose vials of DTwP-Hib, a fully liquid quadravalent vaccine and their comparison with TETRAct-Hib vaccine in Indian infants aged 6-14 weeks.

Both WHO and IAP encourage using combination vaccines, wherever feasible. The phase III trial reported here was conducted to assess and compare the immunogenicity, tolerability and safety of two quadravalent vaccines, Quadrovax(®) (new vaccine), and TETRAct-Hib(®) (available in the market) in a multicentre study, in India. In all, 361 infants aged 6-8 weeks were enrolled, out of which 339 completed the study. The vaccination was done at 6-10-14 weeks following EPI/WHO recommended immunization schedule. Blood samples were collected prior to the administration of first dose and one month after the third dose. Postvaccination, geometric mean titres for each component did not differ significantly between the single dose vial and multi dose vial subgroups and among the two study groups. Adverse events observed were within the range quoted in literature. Quadrovax(®) vaccine manufactured by SIIL was found to be safe, immunogenic and non-inferior to the comparator vaccine. The quadravalent vaccine is best recommended in the second year of life when children receive their booster dose at 15-18 months. It can be given to infants during primary immunization series at 6, 10 and 14 weeks of age when Hepatitis B vaccine is given in a separate arm or to infants at 10 weeks who receive the Hepatitis B vaccine separately following the 0, 6 and 14 weeks or 0, 1 and 6 months schedule.

Immunogenicity and reactogenicity of diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus and Haemophilus influenzae type B.

Immunogenicity and reactogenicity of primary vaccination with combined diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) vaccine when co-administered with Haemophilus influenzae (Hib) conjugate vaccine were assessed in 60 healthy infants. Infants received HBV vaccine at birth, then DTPa-HBV-IPV and Hib vaccines at age 1.5 months, 3.5 months and 6 months. Blood samples were collected before the first DTPa-HBV-IPV and Hib vaccine doses and 1 month after dose 3. Reactogenicity was assessed using diary cards. One month after primary vaccination, all infants were seroprotected/seropositive against all vaccine antigens evaluated. The poliovirus antigen could not be evaluated. The vaccines were well tolerated. No case of fever > 39.0 °C was reported. No serious adverse events were considered related to vaccination. Primary vaccination with DTPa-HBV-IPV and Hib vaccines was immunogenic and well tolerated. Combined vaccines, such as this pentavalent vaccine, minimize the number of injections and vaccination visits required to complete primary vaccination, and provide choice and flexibility for physicians and vaccine providers.

Femoral neuropraxia after vaccination in a 3-month-old infant: a case report.

We report an incidence of a 3-month-old infant who developed femoral neuropraxia after vaccination (diphtheria, tetanus and acellular pertussis/inactivated poliovirus/haemophilus influenzae type B vaccine) in the thigh. To the best of our knowledge, femoral nerve injury after vaccination has not been reported in the literature before. However, this baby made good neurological recovery within 8 weeks after vaccination.

Evaluation of the safety and immunogenicity of the RTS,S/AS01E malaria candidate vaccine when integrated in the expanded program of immunization.

BACKGROUND: The RTS,S/AS01(E) malaria candidate vaccine is being developed for immunization of African infants through the Expanded Program of Immunization (EPI). METHODS: This phase 2, randomized, open, controlled trial conducted in Ghana, Tanzania, and Gabon evaluated the safety and immunogenicity of RTS,S/AS01(E) when coadministered with EPI vaccines. Five hundred eleven infants were randomized to receive RTS,S/AS01(E) at 0, 1, and 2 months (in 3 doses with diphtheria, tetanus, and whole-cell pertussis conjugate [DTPw]; hepatitis B [HepB]; Haemophilus influenzae type b [Hib]; and oral polio vaccine [OPV]), RTS,S/AS01(E) at 0, 1, and 7 months (2 doses with DTPwHepB/Hib+OPV and 1 dose with measles and yellow fever), or EPI vaccines only. RESULTS: The occurrences of serious adverse events were balanced across groups; none were vaccine-related. One child from the control group died. Mild to moderate fever and diaper dermatitis occurred more frequently in the RTS,S/AS01(E) coadministration groups. RTS,S/AS01(E) generated high anti-circumsporozoite protein and anti-hepatitis B surface antigen antibody levels. Regarding EPI vaccine responses upon coadministration when considering both immunization schedules, despite a tendency toward lower geometric mean titers to some EPI antigens, predefined noninferiority criteria were met for all EPI antigens except for polio 3 when EPI vaccines were given with RTS,S/AS01(E) at 0, 1, and 2 months. However, when antibody levels at screening were taken into account, the rates of response to polio 3 antigens were comparable between groups. CONCLUSION: RTS,S/AS01(E) integrated in the EPI showed a favorable safety and immunogenicity evaluation. Trial registration. ClinicalTrials.gov identifier: NCT00436007 . GlaxoSmithKline study ID number: 106369 (Malaria-050).

Differences in the immune response to hepatitis B and Haemophilus influenzae type b vaccines in Guatemalan infants by ethnic group and nutritional status.

Ladino and native Indian Guatemalan infants developed high rates (96-100%) of protective antibodies after receiving conjugate Haemophilus influenzae type b and hepatitis B vaccines at 2, 4 and 6 months of age. Native Indian infants developed significantly (p<0.01) higher geometric mean anti-PRP (polyribose-ribitol-phosphate) and anti-HBs (anti-hepatitis b surface) antibody concentrations than Ladino infants. Malnourished infants generally responded as well as healthy infants. Unvaccinated native Indian infants had higher rates of developing anti-PRP antibodies than Ladino infants by seven months of age.

Immunology of combining CRM(197) conjugates for Streptococcus pneumoniae, Neisseria meningitis and Haemophilus influenzae in Chilean infants.

We evaluated the immunogenicity and safety of an investigational combination of 9-valent pneumococcal conjugate vaccine (PCV9) and meningococcal group C conjugate (MnCC) vaccine (PCV9-MnCC) administered concomitantly with Haemophilus influenzae type b (Hib) conjugate vaccine, and of a combination of the three vaccines mixed together as a single injection (Hib-PCV9-MnCC), and compared them to separately administered PCV9 and MnCC dispensed to Chilean infants at 2, 4, and 6 months of age. The frequency of adverse events was similar among groups. Recipients of PCV9 alone or in combination with the other vaccines mounted significant antibody responses to the nine pneumococcal serotypes in PCV9, with >88% achieving protective levels of > or =0.35microg/mL. For serotypes 6B, 9V, and 5, recipients of PCV9 alone had significantly higher geometric mean concentrations (GMCs) than those of the other vaccine groups. Similarly, the GMC of anti-PRP antibodies was significantly lower among recipients of Hib-PCV9-MnCC than among those who received Hib vaccine separately from PCV9 or MnCC. In Chilean infants, PCV9, PCV9-MnCC, and Hib-PCV9-MnCC were highly immunogenic and safe. Overall, interactions of PCV9, MnCC and Hib affected the magnitude (GMC) of the primary antibody responses to some of the antigens, but not the percentage of subjects who achieved protective antibody thresholds.

Routine vaccination against pertussis and the risk of childhood asthma: a population-based cohort study.

BACKGROUND: In industrialized countries vaccination coverage remains suboptimal, partly because of perception of an increased risk of asthma. Epidemiologic studies of the association between childhood vaccinations and asthma have provided conflicting results, possibly for methodologic reasons such as unreliable vaccination data, biased reporting, and reverse causation. A recent review stressed the need for additional, adequately controlled large-scale studies. OBJECTIVE: Our goal was to determine if routine childhood vaccination against pertussis was associated with subsequent development of childhood wheezing disorders and asthma in a large population-based cohort study. METHODS: In 6811 children from the general population born between 1993 and 1997 in Leicestershire, United Kingdom, respiratory symptom data from repeated questionnaire surveys up to 2003 were linked to independently collected vaccination data from the National Health Service database. We compared incident wheeze and asthma between children of different vaccination status (complete, partial, and no vaccination against pertussis) by computing hazard ratios. Analyses were based on 6048 children, 23 201 person-years of follow-up, and 2426 cases of new-onset wheeze. RESULTS: There was no evidence for an increased risk of wheeze or asthma in children vaccinated against pertussis compared with nonvaccinated children. Adjusted hazard ratios comparing fully and partially vaccinated with nonvaccinated children were close to one for both incident wheeze and asthma. CONCLUSION: This study provides no evidence of an association between vaccination against pertussis in infancy and an increased risk of later wheeze or asthma and does not support claims that vaccination against pertussis might significantly increase the risk of childhood asthma.

Concomitant use of the 3-dose oral pentavalent rotavirus vaccine with a 3-dose primary vaccination course of a diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio-Haemophilus influenzae type b vaccine: immunogenicity and reactogenicity.

BACKGROUND: The pentavalent rotavirus vaccine (PRV), RotaTeq, can be concomitantly administered with most routine childhood vaccines. This study evaluated the immunogenicity and reactogenicity of PRV when used concomitantly with a hexavalent vaccine containing diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliovirus, and Haemophilus influenzae type b. METHODS: Healthy infants (N = 403) received hexavalent vaccine concomitantly with either PRV or placebo at 2, 3, and 4 months of age. Antibody responses were measured immediately before and 42 +/- 3 days after vaccination. Parents/legal guardians recorded all adverse events for 14 days after vaccination. RESULTS: Seroprotective titers for hepatitis B (hepatitis B surface antigen > or =10 mIU/mL) were achieved by 97.8% of subjects in both vaccine treatment groups. Seroprotective titers to H. influenzae type b (polyribosylribitol phosphate > or =0.15 microg/mL) were achieved by 91.4% of subjects receiving both vaccines and 95.1% of subjects receiving only hexavalent vaccine. Seroprotective titers to diphtheria, tetanus, and poliovirus were also comparable between the vaccine treatment groups, as were geometric mean antibody titers to the pertussis antigens. Among PRV recipients, 92% had a > or =3-fold rise in serum antirotavirus immunoglobulin A levels. Concomitant administration was well tolerated. The incidence of adverse events was similar for both groups, with no statistically significant increases in fever, vomiting, diarrhea, or irritability. CONCLUSIONS: In this study, concomitant administration of PRV with hexavalent vaccine was well tolerated and the immune responses to the antigens of the hexavalent vaccine were noninferior when compared with those of the control group. In addition, PRV was immunogenic when administered concomitantly with hexavalent vaccine.

Neither antibody to a group B streptococcal conjugate vaccine nor the vaccine itself is teratogenic in rabbits.

Group B Streptococcus (GBS) is a leading cause of human neonatal bacterial disease, resulting in pneumonia, sepsis, meningitis and sometimes, death. Supportive preclinical studies of GBS capsular polysaccharide (CPS)-protein conjugate vaccines have led to several phase 1 and phase 2 trials in healthy, non-pregnant adults, which demonstrated that the vaccines, produced at the Channing Laboratory, were safe and immunogenic. However, evaluation of the safety and immunogenicity of a GBS conjugate vaccine administered to pregnant women demanded that it be manufactured under current good manufacturing practices (cGMP) and that it undergo developmental toxicity evaluation. In this report, we describe a GBS type III CPS-tetanus toxoid (III-TT) vaccine lot 3-1-96 manufactured and vialed under cGMP and our evaluation of the effect of this vaccine and of GBS type III CPS-specific antibody on conception and early- and late-stage fetal development in rabbits. III-TT lot 3-1-96 was compositionally similar to prototype III-TT lot 91-1, produced under non-GMP, and was potent in a mouse maternal vaccination-neonatal pup challenge model of GBS disease. Four groups of 30 female rabbits each were randomized to receive III-TT lot 3-1-96 vaccine, saline-alum, or combinations of these treatments before and after insemination. The dose of conjugated CPS on a weight basis was 1 microg/kg, mimicking the anticipated actual human dose. Based on the weight of the rabbits, this was 20- to 100-fold greater than the expected human dose. Does were pre-assigned to deliver litters naturally or have their kits delivered by Caesarean-section at gestation day 29, to assess late fetal development. Sera from does and kits were collected, and the presence of type III CPS-specific IgG was confirmed by quantitative ELISA. Based on all assessments, GBS type III-TT lot 3-1-96, nor antibody to it did not affect embryo fetal viability, sex ratio, growth or cause malformations (i.e., it was non-teratogenic). In addition, that III-TT lot 3-1-96 was found to be safe and immunogenic in two clinical studies involving healthy non-pregnant adults supports a clinical evaluation of this vaccine in pregnant women.

Host/parasite interactions in bacterial endophthalmitis.

Bacterial infections within the eye arise as complications of intraocular surgery, penetrating injury, or hematogenous spread from distant anatomical sites. Because: 1) the interior surfaces of the eye are lined with sensitive, nonregenerating tissues, 2) the inner chambers of the eye are relatively sequestered from circulating immunological components, 3) the integrity of blood-ocular barriers provides poor penetration of systemically administered antibiotics, and 4) aqueous and vitreous humor represent rich, relatively acellular culture media; endophthalmitis often progresses rapidly and total loss of vision frequently results. Years of clinical experience have shown that current therapies for endophthalmitis, including antimicrobials, antiinflammatory agents, and vitrectomy, are frequently unsuccessful in ameliorating destruction of intraocular tissues. While bacterial and host factors were thought to play key roles in the course and severity of endophthalmitis, it is only recently that their contributions have been experimentally defined. Molecular-based techniques are gaining increased use in the study of infectious eye diseases. Current findings regarding the host/parasite interactions within the eye are reviewed, and a resulting integrative model of the natural course of endophthalmitis proposed. A molecular-level understanding of the roles of both bacterial and host factors during endophthalmitis will likely reveal potential targets for therapeutic intervention aimed at salvaging vision.

[Pathogenesis of lung damage caused by Pasteurella haemolytica]. / Patogénesis del daño pulmonar provocado por Pasteurella haemolytica.

Pneumonic pasteurellosis is the major economic problem of the cattle industry in North America. This disease is characterized by an acute, severe, fibrinonecrotic pleuropneumonia. Pasteurella haemolytica A1 is commonly isolated from these pneumonic lesions. It has been demonstrated that stress or viral infection compromises defense mechanisms of the upper respiratory tract and lung, predisposing to an initial multiplication of bacteria in the nasopharynx and, subsequently, lungs are deluged with large numbers of bacteria. Once multiplication in the alveoli has begun, virulence factors exert their influence to induce an excessive host inflammatory response that results in severe tissue damage. Despite a large number of studies conducted to explore the complex interaction between P. haemolytica and the host response, there still remains a lack of detailed understanding. This review discusses evidence of the role of the main virulence factors of P. haemolytica on the pathogenesis of pulmonary damage.