Reactogenicity Data Research Articles

A randomized clinical trial in adults and newborns in South Africa to compare the safety and immunogenicity of bacille Calmette-Guérin (BCG) vaccine administration via a disposable-syringe jet injector to conventional technique with needle and syringe

IntroductionIntradermal bacille Calmette-Guérin (BCG) vaccination by needle-free, disposable-syringe jet injectors (DSJI) is an alternative to the Mantoux method using needle and syringe (NS). We compared the safety and immunogenicity of BCG administration via the DSJI and NS techniques in adults and newborn infants at the South African Tuberculosis Vaccine Initiative (SATVI) research site in South Africa. MethodThirty adults and 66 newborn infants were randomized 1:1 to receive intradermal BCG vaccine (0.1mL in adults; 0.05mL in infants) via DSJI or NS. Wheal diameter (mm) and skin fluid deposition at the site of injection (SOI) were measured immediately post-vaccination. Adverse events and SOI reactogenicity data were collected 30min and 1, 2, 4, and 12 weeks after vaccination for adults and at 30min and 4, 10, and 14 weeks for infants. Blood was collected in infants at 10 and 14 weeks to assess BCG-specific T-cell immune responses. ResultsMore infant BCG vaccinations by DSJI deposited >5μL fluid on the skin surface, compared to NS (49% versus 9%, p=0.001). However, all 12 infant vaccinations that did not produce any SOI wheal occurred in the NS group (36%, p<0.001). Median wheal diameter, in participants for which an SOI wheal formed, did not differ significantly between groups in infants (combined 3.0mm IQR 2.0 to 4.0, p=0.59) or in adults (combined 9.0mm IQR 7.0 to 10.0, p=0.13). Adverse events were similar between study arms. Proportion of participants with BCG scars after three months did not differ in adults (combined 97%, p=0.67) or infants (combined 62%, p=0.13). Frequencies of BCG-specific clusters of differentiation 4 (CD4) and clusters of differentiation 8 (CD8) T-cells co-expressing IFN-γ, TNF-α, IL-2, and/or IL-17 were not different in the DSJI and NS groups. ConclusionBCG vaccination of newborn infants via DSJI was more likely to deliver an appropriate intradermal wheal at the SOI as compared to NS, despite leaving more fluid on the surface of the skin. Safety, reactogenicity, and antigen-specific T-cell immune responses did not differ between DSJI and NS techniques.

Safety and Tolerability of Conserved Region Vaccines Vectored by Plasmid DNA, Simian Adenovirus and Modified Vaccinia Virus Ankara Administered to Human Immunodeficiency Virus Type 1-Uninfected Adults in a Randomized, Single-Blind Phase I Trial

Trial DesignHIV-1 vaccine development has advanced slowly due to viral antigenic diversity, poor immunogenicity and recently, safety concerns associated with human adenovirus serotype-5 vectors. To tackle HIV-1 variation, we designed a unique T-cell immunogen HIVconsv from functionally conserved regions of the HIV-1 proteome, which were presented to the immune system using a heterologous prime-boost combination of plasmid DNA, a non-replicating simian (chimpanzee) adenovirus ChAdV-63 and a non-replicating poxvirus, modified vaccinia virus Ankara. A block-randomized, single-blind, placebo-controlled phase I trial HIV-CORE 002 administered for the first time candidate HIV-1- vaccines or placebo to 32 healthy HIV-1/2-uninfected adults in Oxford, UK and elicited high frequencies of HIV-1-specific T cells capable of inhibiting HIV-1 replication in vitro. Here, detail safety and tolerability of these vaccines are reported.MethodsLocal and systemic reactogenicity data were collected using structured interviews and study-specific diary cards. Data on all other adverse events were collected using open questions. Serum neutralizing antibody titres to ChAdV-63 were determined before and after vaccination.ResultsTwo volunteers withdrew for vaccine-unrelated reasons. No vaccine-related serious adverse events or reactions occurred during 190 person-months of follow-up. Local and systemic events after vaccination occurred in 27/32 individuals and most were mild (severity grade 1) and predominantly transient (<48 hours). Myalgia and flu-like symptoms were more strongly associated with MVA than ChAdV63 or DNA vectors and more common in vaccine recipients than in placebo. There were no intercurrent HIV-1 infections during follow-up. 2/24 volunteers had low ChAdV-63-neutralizing titres at baseline and 7 increased their titres to over 200 with a median (range) of 633 (231-1533) post-vaccination, which is of no safety concern.ConclusionsThese data demonstrate safety and good tolerability of the pSG2.HIVconsv DNA, ChAdV63.HIVconsv and MVA.HIVconsv vaccines and together with their high immunogenicity support their further development towards efficacy studies.Trial RegistrationClinicalTrials.gov NCT01151319

Safety and reactogenicity of BCG revaccination with isoniazid pretreatment in TST positive adults

RationaleGlobal tuberculosis (TB) control may require mass vaccination with a new TB vaccine, such as a recombinant bacille Calmette Guerin (BCG) or attenuated Mycobacterium tuberculosis (MTB). The safety profile of live mycobacterial vaccines in latently infected adults with prior infant BCG vaccination is unknown. ObjectivesEvaluate safety and reactogenicity of BCG revaccination, with or without isoniazid (INH) pretreatment, in adults with latent MTB infection (LTBI). MethodsEighty-two healthy, HIV uninfected, South African adults, with a BCG scar and tuberculin skin test (TST) diameter ≥15mm, were randomized to receive 6 months of INH, starting either before, or 6 months after, intradermal revaccination with BCG Vaccine SSI (Statens Serum Institut, Copenhagen). Safety and reactogenicity data are reported through 3 months post BCG revaccination. ResultsBaseline characteristics were similar between treatment arms. Mean baseline TST diameter was 20±4mm. Seventy-two subjects received BCG revaccination. Injection site erythema (68%) and induration (86%) peaked 1 week after revaccination. Ulceration (76%) peaked at 2 weeks, and resolved by 3 months in all but 3 subjects. Diameter of ulceration was >10mm in only 8%, but a residual scar was common (85%). No regional lymphadenitis or serious morbidity related to BCG was seen. Reactogenicity was not affected by INH pretreatment. ConclusionBCG revaccination of MTB infected adults is safe, well tolerated, and reactogenicity is similar to that of primary BCG vaccination. Clinical trials of live recombinant BCG or attenuated MTB vaccines may be considered in latently infected adults, with or without INH pretreatment (ClinicalTrials.gov identifier: NCT01119521).

A phase 2 open-label safety and immunogenicity study of a meningococcal B bivalent rLP2086 vaccine in healthy adults

BackgroundNeisseria meningitidis serogroup B (MnB) is a leading cause of bacterial meningitis and septicemia in adolescents and young adults. No currently licensed and available vaccine has been shown to provide broad protection against endemic MnB disease. A bivalent rLP2086 vaccine based on two factor H-binding proteins (fHBPs) has been developed to provide broad protection against MnB disease-causing strains. MethodsThis study assessed the safety and immunogenicity of the final formulation of a bivalent rLP2086 vaccine in 60 healthy adults (18–40 years of age) receiving 120μg doses at 0, 1, and 6 months. Safety was assessed by collecting solicited reactogenicity data and participant-reporting of adverse events. Immunogenicity was evaluated by human serum bactericidal assay (hSBA) against 5 MnB strains expressing distinct fHBP variants and fHBP-specific immunoglobulin G titre. ResultsAfter each immunisation, local reactions such as pain at the injection site and erythema were generally mild or moderate. The most common vaccine-related adverse event was upper respiratory tract infection, which was reported by two participants. Seroprotection (hSBA titres≥1:4) was achieved in 94.3% of participants against a MnB strain expressing the vaccine-homologous fHBP variant A05 and 70.0%–94.7% against MnB strains expressing the heterologous fHBP variants B02, A22, B44, and B24. Seroconversion rates (≥4-fold rise in hSBA titres) ranged from 70.0% to 94.7% across the five MnB test strains following the 3-dose vaccination regimen. Immunogenicity responses tended to increase upon subsequent vaccine doses. ConclusionsBivalent rLP2086 is a promising vaccine candidate for broad protection against MnB disease-causing strains.

An investigation of three injections techniques in reducing local injection pain with a human papillomavirus vaccine: A randomized trial

BackgroundPrevious research suggests vaccine injection technique can influence local reactogenicity. ObjectiveTo identify characteristics of vaccination technique and individual vaccinees associated with frequency and severity of pain on injection and local reactogenicity following immunisation with quadrivalent human papillomavirus vaccine. DesignRandomised cross-over trial of three injection techniques. Data were collected on health history, perceived stress and social support using a 10 item perceived stress scale and a single item social support question. Pain on injection was measured using a visual analogue scale and reactogenicity data was collected using participant-held diaries. SettingClinic rooms at the University of Auckland. ParticipantsFemales aged 14–45 years and males aged 14–26 years recruited to the study. Main outcome measuresPrimary outcome measures were perceived pain on injection and the local injection site reactions pain, erythema, swelling and induration. ResultsThe three injection techniques did not affect injection site reactogenicity. Females tended to experience more reactogenicity. Perceived stress, social support and atopy were not associated with reactogenicity outcomes and exercise showed little effect. No variables, including injection technique, were associated with wide variation in perceived pain in injection. Case by case observational data suggest some variations in anatomical site may be important. ConclusionsMost injection site reactions in this study were mild. The three injection techniques used in this study were equivalent in their reactogenicity and pain profiles and could be recommended for use in this population.

A randomized, dose-ranging assessment of the immunogenicity and safety of a booster dose of a combined diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b (DTPw-HBV-IPV/Hib) vaccine vs. co-administration of DTPw-HBV/Hib and IPV vaccines in 12 to 24 months old Filipino toddlers

As progress toward global poliovirus eradication continues, more and more countries are moving away from use of oral poliovirus vaccines (OPV) to inactivated poliovirus vaccines (IPV) in national vaccination schedules. Reduction of antigen dose in IPV could increase manufacturing capacity and facilitate the change from OPV to IPV. Combination vaccines reduce the number of injections required to complete vaccination, thus playing an important role in maintaining high vaccine coverage with good public acceptability. Three formulations of a combined, candidate hexavalent diphtheria-tetanus-whole cell pertussis-hepatitis B-inactivated poliovirus-Hemophilus influenzae type b conjugate vaccine (DTPw-HBV-IPV/Hib, GlaxoSmithKline Biologicals) differing only in IPV antigen content (full-dose, half-dose and one-third dose as compared with available stand-alone IPV vaccines), were evaluated when administered to healthy toddlers. Controls received separately administered licensed DTPw-HBV/Hib and IPV vaccines. Immunogenicity was assessed before and one month after vaccination. Safety and reactogenicity data were assessed for 30 d after vaccination. A total of 312 Filipino children were vaccinated in their second year of life. Each DTPw-HBV-IPV/Hib formulation was non-inferior to control in terms of pre-defined criteria for IPV immunogenicity. Post-vaccination GMTs against each poliovirus type were increased between 4.2- and 37.9-fold over pre-vaccination titers. Non-inferiority to other vaccine antigens was also demonstrated. The safety profile of the 3 DTPw-HBV-IPV/Hib formulations resembled licensed DTPw-HBV/Hib Kft and IPV in terms of the frequency and intensity of adverse reactions after vaccination. Further investigation of DTPw-HBV-IPV/Hib containing reduced quantity of IPV antigen for primary vaccination in infants is warranted. This study is registered at www.clinicaltrials.gov NCT number: NCT01106092

H1N1 Antibody Persistence 1 Year After Immunization With an Adjuvanted or Whole-Virion Pandemic Vaccine and Immunogenicity and Reactogenicity of Subsequent Seasonal Influenza Vaccine: A Multicenter Follow-on Study

We investigated antibody persistence in children 1 year after 2 doses of either an AS03(B)-adjuvanted split-virion or nonadjuvanted whole-virion monovalent pandemic influenza vaccine and assessed the immunogenicity and reactogenicity of a subsequent dose of trivalent influenza vaccine (TIV). Children previously immunized at age 6 months to 12 years in the original study were invited to participate. After a blood sample was obtained to assess persistence of antibody against swine influenza A/H1N1(2009) pandemic influenza, children received 1 dose of 2010/2011 TIV, reactogenicity data were collected for 7 days, and another blood sample was obtained 21 days after vaccination. Of 323 children recruited, 302 received TIV. Antibody persistence (defined as microneutralization [MN] titer ≥1:40) 1 year after initial vaccination was significantly higher in the AS03(B)-adjuvanted compared with the whole-virion vaccine group, 100% (95% confidence interval [CI], 94.1%-100%) vs 32.4% (95% CI, 21.5%-44.8%) in children immunized <3 years old and 96.9% (95% CI, 91.3%-99.4%) vs 65.9% (95% CI, 55.3%-75.5%) in those 3-12 years old at immunization, respectively (P < .001 for both groups). All children receiving TIV had post-vaccination MN titers ≥1:40. Although TIV was well tolerated in all groups, reactogenicity in children <5 years old was slightly greater in those who originally received AS03(B)-adjuvanted vaccine. This study provides serological evidence that 2 doses of AS03(B)-adjuvanted pandemic influenza vaccine may be sufficient to maintain protection across 2 influenza seasons. Administration of TIV to children who previously received 2 doses of either pandemic influenza vaccine is safe and is immunogenic for the H1N1 strain.

A 1-year follow-on study from a randomised, head-to-head, multicentre, open-label study of two pandemic influenza vaccines in children

Pandemic influenza A H1N1 infections occurred worldwide from 2009. Children were particularly vulnerable. Novel vaccines were used during the pandemic. To assess the persistence of antibody to H1N1 influenza 1 year after children aged 6 months to 12 years had been immunised with two doses of either a non-adjuvanted whole-virion H1N1 influenza vaccine or an AS03B-adjuvanted split-virion H1N1 influenza vaccine; and also to assess the immunogenicity and reactogenicity in this population of a single dose of 2010-11 trivalent seasonal influenza vaccine. Multicentre, open-label, follow-on from randomised, head-to-head trial. Five UK sites (Southampton, Oxford, Bristol, London and Exeter). Children who completed last year's head-to-head randomised study were invited to participate. Children who had subsequently received a further dose of H1N1 vaccine, or who had already received a dose of 2010-11 trivalent seasonal influenza vaccine, were excluded. In the previous study, children were randomised (in a 1 : 1 ratio) to receive two doses, 21 days apart, of either a non-adjuvanted whole-virion H1N1 influenza vaccine or an AS03B-adjuvanted split-virion H1N1 influenza vaccine. In this follow-on study, a blood sample was taken to assess the persistence of antibody 1 year later, followed by administration of one 0.5 ml-dose of trivalent seasonal influenza vaccine. A second blood sample was taken 3 weeks later. Comparison between vaccines of the percentage of participants with a microneutralisation (MN) titre ≥ 1 : 40 and a haemagglutination titre ≥ 1 : 32, 1 year after vaccination. Immunogenicity of the trivalent seasonal influenza vaccine was assessed 3 weeks after vaccination by both the MN and the haemagglutination inhibition (HI) titres. Reactogenicity data were recorded for 7 days after vaccination. A total of 323 children were enrolled and 318 were included in the analysis of the persistence of antibody. One year after receipt of whole-virion vaccine, the MN titre was ≥ 1 : 40 in 32.4% of those vaccinated when < 3 years old and in 65.9% of those vaccinated when ≥ 3 years old; the HI titre was ≥ 1 : 32 in 63.2% and 79.1% of children in the respective age groups. One year after receipt of the adjuvanted vaccine, the MN titre was ≥ 1 : 40 in 100% of those vaccinated when < 3 years old and in 96.9% of those vaccinated when ≥ 3 years old; the HI titre was ≥ 1 : 32 in 98.4% and 96.9% of children in the respective age groups. Three hundred and two children were given trivalent seasonal influenza vaccination. Three weeks later, sera were obtained from 282 children; 100% had an MN titre ≥ 1 : 40 and HI titre ≥ 1 : 32. Trivalent seasonal influenza vaccine was well tolerated, although in children < 5 years old, fever ≥ 38 °C was reported in 13.6% of those who had previously received whole-virion vaccine, and in 18.3% of those who had received adjuvanted vaccine. Nearly all children who received two doses of AS03B-adjuvanted split-virion pandemic H1N1 influenza vaccine had titres of antibody deemed protective (HI titre ≥ 1 : 32, MN titre ≥ 1 : 40) 1 year later. Children who received two doses of whole-virion vaccine had lower titres, although many were above the putative protective thresholds. One year after either pandemic vaccine, the 2010-11 trivalent seasonal influenza vaccine produced a marked serological response to the H1N1 component of the vaccine and was well tolerated. We propose to investigate whether or not previous receipt of monovalent influenza vaccines affected serological response to the H3N2 and B components of the 2010-11 seasonal influenza vaccine, using stored sera. ClinicalTrials.gov NCT01239537. The National Institute for Health Research Health Technology Assessment programme.

Human papillomavirus 16/18 AS04-adjuvanted cervical cancer vaccine: immunogenicity and safety in 15-25 years old healthy Korean women

ObjectiveThe study assessed the immunogenicity and safety of human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in healthy Korean women aged 15-25 years.MethodsPhase IIIB, double-blind, randomised (2:1), multi-centre trial was conducted in Korea from June 2007 to March 2008. The study enrolled 225 women in the HPV (N=149) and placebo (N=76) groups who received three doses of HPV-16/18 AS04-adjuvanted vaccine or placebo (aluminium hydroxide) administered intramuscularly at 0, 1, and 6 months and were followed until one month post-dose 3. Serum samples were collected pre-vaccination and one month post-dose 3. Safety and reactogenicity data were collected throughout.ResultsIn this trial, 208 women completed the study (141 in HPV group; 67 in placebo group). At month 7, all initially seronegative women had seroconverted for HPV-16 and HPV-18 antibodies with anti-HPV-16 and anti-HPV-18 geometric mean titres of 9,351.4 El.U/mL (95% CI, 8,145.5 to 10,735.8) and 4204.1 El.U/mL (95% CI, 3,626.5 to 4,873.6), respectively. Initially seropositive women showed similar increase in geometric mean titre levels. Compliance to the three dose vaccination course was 95.3% in HPV and 89.5% in placebo group. Solicited local (pain) and general (fatigue, myalgia or headache) symptoms were commonly reported in both groups. Three serious adverse events were reported (two in HPV group; one in placebo group), all unrelated to vaccination by the investigator; all recovered.ConclusionThe HPV-16/18 AS04-adjuvanted vaccine was highly immunogenic with a clinically acceptable safety profile in Korean women. This study was in line with previous global studies in Europe, North America, and Brazil. (ClinicalTrials.gov number, NCT 00485732.)

Safety and immunogenicity of AS03B adjuvanted split virion versus non-adjuvanted whole virion H1N1 influenza vaccine in UK children aged 6 months-12 years: open label, randomised, parallel group, multicentre study

Objectives To compare the safety, reactogenicity, and immunogenicity of an adjuvanted split virion H1N1 vaccine and a non-adjuvanted whole virion vaccine used in the pandemic immunisation programme in the United...

Evaluation of the safety, reactogenicity and immunogenicity of FluBlok ® trivalent recombinant baculovirus-expressed hemagglutinin influenza vaccine administered intramuscularly to healthy children aged 6–59 months

Background Recombinant baculovirus-expressed hemagglutinin (rHA [FluBlok ®]) influenza vaccine is unique in avoiding production in eggs and its rapid production capability. Objective Compare the safety and immunogenicity of trivalent FluBlok to egg-grown trivalent influenza vaccine (TIV) in children. Methods Healthy children were randomized to receive two doses of study vaccines. TIV (7.5 μg HA/antigen), FluBlok-22.5 (22.5 μg rHA/antigen), or FluBlok-45 (45 μg rHA/antigen) were given to 115 children ages 6–35 months. TIV (15 μg HA/antigen) or FluBlok-45 was given to 41 children ages 36–59 months. Safety and reactogenicity data were collected post-vaccination. Serum hemagglutination-inhibition antibody (HI) titers were measured before and 28 days after vaccination. Results No serious vaccine-related adverse events occurred and reactogenicity events to equal volumes of TIV or FluBlok were generally similar. However, in the younger children, selected local and systemic symptoms were recorded significantly more frequently to 0.5 mL FluBlok-45 than to 0.25 mL doses of either the FluBlok-22.5 or 7.5 μg TIV vaccines. In the younger children, the immunogenicity to TIV was generally significantly superior to FluBlok. Serologic responses to FluBlok were higher in the older children than the younger group, but were still somewhat lower compared to TIV. Conclusion These data suggests that FluBlok is as safe but less immunogenic than similar volumes of TIV, particularly in the youngest children. The immunogenicity data is the converse of what has been observed in adults. Further studies examining the immunogenicity of FluBlok in older children are warranted.

Combined, Reduced-Antigen Content Tetanus, Diphtheria, and Acellular Pertussis Vaccine (Boostrix®)†

Boostrix is a three-pertussis component, combined, reduced-antigen content tetanus, diphtheria, and acellular pertussis (Tdap) booster vaccine administered as a single intramuscular dose in adolescents or adults aged 10-64 years. Large, well designed trials conducted in the US in adolescents aged 10-18 years and in adults aged 19-64 years showed that serum concentrations of anti-pertussis antibodies approximately 1 month after Boostrix administration were noninferior to those previously shown to have a protective effect in infants following a primary regimen of combined diphtheria, tetanus, and acellular pertussis (DTaP) vaccine. Protective serum concentrations of anti-diphtheria and anti-tetanus antibodies were achieved in essentially all (>or=99.9%) adolescents randomized to receive Boostrix or tetanus and diphtheria toxoids (Td) vaccine, and Boostrix was noninferior to Td vaccine for these endpoints. Similarly high seroprotection rates against diphtheria and tetanus were demonstrated with Boostrix and a five-pertussis component Tdap booster vaccine (Adacel) in a large, randomized study in adults; Boostrix was noninferior to Adacel for these outcomes. Reactogenicity data indicate that the vaccine is generally well tolerated in terms of solicited local and general symptoms in both adults and adolescents. Moreover, the importance of single-dose booster vaccination with a Tdap vaccine (such as Boostrix) in these populations is highlighted in current immunization guidelines. Therefore, as a single-dose booster vaccine, Boostrix provides a useful option to reduce pertussis morbidity and maintain the standard of care for tetanus and diphtheria protection in individuals aged 10-64 years.

Safety profile of pneumococcal conjugate vaccines: systematic review of pre-and post-licensure data

A 7-valent pneumococcal polysaccharide-protein conjugate vaccine (PCV7) was licensed in the United States of America in 2000, but no comprehensive postmarketing review of safety has been carried out. We conducted a systematic review of the safety of PCV7 and other pneumococcal conjugate vaccines. A total of 42 studies were included in the review. Reactogenicity data from some randomized trials suggest that PCV7 may result in more local reactions and fever than certain comparison vaccines. However, the reactions were mild and self-limited, and PCV7 did not carry an increased risk of severe injection-site reactions or high fever. Some, although not all, of the randomized trials in children found that mild local and systemic reactions associated with PCV7 may increase with the number of doses, at least over the three-dose primary series. In addition, PCV7 and other pneumococcal conjugate vaccines were found to have tolerable reactogenicity in Native American and African populations and in medically high-risk groups for which pneumococcal vaccination is recommended. Two of the largest studies of PCVs, one involving PCV7 and the other, PCV9, found a statistically significant increased risk of hospitalization for reactive airway disease, including asthma. Another large trial of PCV9, however, did not find an increased risk of asthma. In conclusion, this review of the evidence did not identify any major safety problems with PCV7 or any other pneumococcal conjugate vaccine, with the possible exception of reactive airway disease, which may bear further scrutiny as additional data become available.

Tdap is not associated with excessive reactogenicity in adolescents who received five prior doses of acellular pertussis vaccine

Zepp et al provide the first substantial study of safety of administration of a sixth dose of an acellular pertussis antigen-containing vaccine. Since the recommendation in the United States in 1997 for universal use of acelluar pertussis vaccine (aP) instead of whole-cell pertussis vaccine (wP) for all 5 doses in the DTaP series through 6 years of age, reactogenicity (redness, swelling and pain at the injection site; or fever and systemic adverse events; or both within 48 hours of administration) is markedly reduced. As the cohort of children fully immunized solely with aP-containing vaccines has grown, increased reactogenicity after the fourth and fifth doses (still considerably less than after wP-containing vaccines) has been noted. In 2005, two vaccines with tetanus toxoid and reduced-content diphtheria toxoid and acellular pertussis antigens (Tdap) were licensed in the United States and recommended for universal administration in adolescents in order to boost waned immunity. There was a modicum of concern from reactogenicity data following the fifth dose of DTaP in children that a Tdap in adolescents (the sixth dose of an acellular-pertussis containing vaccine) could be associated with heightened reactogenicity. Zepp et al provide reassuring data of only minor reactogenicity following Tdap among study subjects who also had been study subjects for the preceding 5 doses of DTaP. This was true even for subjects who had substantial reactions after the fifth dose. Halperin’s editorial brings into focus the expected safety, benefit, and challenges of using repeated doses of Tdap to curb the rising incidence of pertussis in adolescents and adults, and indirectly to protect very young infants.

Immunogenicity, reactogenicity and safety of a 7-valent pneumococcal conjugate vaccine (PCV7) concurrently administered with a DTPa-HBV-IPV/Hib combination vaccine in healthy infants

Background To evaluate immunogenicity, reactogenicity, and safety of a hexavalent combination vaccine diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- Haemophilus influenzae type b (DTPa-HBV-IPV/Hib) when coadministered with a 7-valent pneumococcal conjugate vaccine (PCV7). Methods Infants received either a hexavalent diphtheria-tetanus-acellular pertussis-hepatitis B-inactivated polio virus- H. influenzae type b vaccine concomitantly with PCV7 or DTPa-HBV-IPV/Hib alone infants were vaccinated at 2, 3 and 4 months (primary immunization) and 12–15 months of age (booster dose). Local and systemic reactions and adverse events were monitored following each dose and compared between groups. Blood was obtained prior to dose 1, one month after dose 3, immediately prior to and 1 month following the booster dose to measure antibody responses to each of the antigens. Results Two hundred and fifty-three subjects (PCV7, 127; Control, 126) were enrolled. Antibody responses were compared in 226 subjects for the primary immunization and 212 for the booster dose (per-protocol (PP) population). Although there were some differences in geometric mean concentrations (GMCs) to the DTPa-HBV-IPV/Hib antigens after the primary series, GMCs for all antigens after the booster dose were similar in both groups, except for diphtheria which was significantly higher in the PCV7 group (PCV7, 7.41 IU/mL; Control, 5.78 IU/mL). Reactogenicity and safety data were compared in 252 infants receiving primary immunization and 235 children receiving the booster dose. Site reactions were similar in both groups. Fever ≥38.0 °C following each vaccination was reported more frequently in the PCV7 group (28.3–50.0%) than in the Control group (15.6–33.6%) whereas fever >39.0 °C occurred only in a few cases and to the same extent in both groups (PCV7, 0.8–2.7%; Control, 1.6–4.1%). Only one reported serious adverse event was characterized as being related to the study vaccines: control subject was hospitalized with a fever. Conclusion DTPa-HBV-IPV/Hib and PCV7 were highly immunogenic, well-tolerated and safe when coadministered at 2, 3 and 4 months of age with a booster dose at 12–15 months of age. These results support the coadministration of PVC7 with DTPa-HBV-IPV/Hib as part of the routine immunization schedule for infants and children.

Safety profile of recombinant canarypox HIV vaccines

Attenuated poxviruses have been developed for use as candidate vaccine vectors. ALVAC, a strain of the Avipoxvirus canarypox, has been extensively evaluated as a vector for vaccines against the human immunodeficiency virus type 1 (HIV-1). This report presents the safety and reactogenicity data derived from 11 multicenter, randomized controlled trials of ALVAC-HIV vaccines conducted by the HIV Vaccine Trials Network (HVTN) and its predecessor, the AIDS Vaccine Evaluation Group (AVEG). Five different ALVAC vaccine constructs were tested among 1497 volunteers. Reactogenicity was similar for different ALVAC constructs. Local reactions of any grade to ALVAC vaccines were common. However, fewer than 2% of vaccinees had severe local responses, and less than 1% experienced severe local pain or tenderness. Systemic responses were mild and transient. As combination vaccine regimens are in common use, we also evaluated side effects of ALVAC vectors given in combination with a recombinant subunit protein. No significant differences were noted in the reactogenicity of ALVAC given with or without a recombinant envelope subunit vaccine. Black, non-Hispanic and male recipients of ALVAC-HIV reported less pain following vaccination than White, non-Hispanics and females, respectively. ALVAC-HIV vaccines are well tolerated at tested doses. The reactogenicity profiles are comparable to those reported for existing vaccines licensed for use among adults. Reactogenicity does not appear to be related to the number or type of inserted genes, and did not vary between different ALVAC constructs.

Safety and efficacy of meningococcal group C conjugate vaccines

The UK was the first country to implement a universal vaccination programme with conjugate polysaccharide vaccines against Neisseria meningitidis group C. This article reviews the pre- and postlicensure data on their efficacy and safety 3 years after the introduction of the programme. Local reactogenicity data compare favourably with other routine vaccinations and no specific increase in adverse reactions has been associated with their use in infant vaccination programmes. Self-limiting systemic reactions such as fever, myalgia, headaches and irritability have commonly been observed in prelicensure studies. Passive postlicensure safety monitoring of suspected adverse reactions has identified a large number of reports, generally of reactions deemed non-serious and reversible. An Expert Working Group has concluded the balance of benefits and risks to be overwhelmingly favourable. Further safety data are expected from large data-linkage studies. Present efficacy estimates, based on active surveillance of case numbers, vaccine failures and coverage rates, are approximately 90% for all age groups. A significant fall in the number of cases attributable to meningococcal group C infection has been observed in the age group of < 20 years. The annual number of fatalities from confirmed meningococcal C disease in the same population has fallen from 67 to 5 cases within a 2-year period.

Incidence of reactions to meningococcal A&C vaccine among U.K. schoolchildren

One thousand and sixty five schoolchildren aged 11 to 18 years were vaccinated against meningococcal meningitis, serogroups A and C, following an outbreak of group C disease at a Lincolnshire comprehensive school. Nine hundred and sixty seven children provided reactogenicity data. Medical events which occurred during the 14 days following vaccination were recorded by the vaccinees by means of a questionnaire. Although 544 (56.3%) reported transient local soreness and 333 (34.4%) reported local redness, only a small number, 32 (3.3%) and 22 (2.3%) respectively, reported localised symptoms lasting more than 72 hours. Other health problems were recorded, noting any absence from school. The problems were wide-ranging, all were minor, and all were typical of those expected in a teenage school population. No serious or unexpected side effects were reported.