Lily Yin Weckx

Efficacy of an Adjuvanted Herpes Zoster Subunit Vaccine in Older Adults

BACKGROUND In previous phase 1-2 clinical trials involving older adults, a subunit vaccine containing varicella-zoster virus glycoprotein E and the AS01B adjuvant system (called HZ/su) had a clinically acceptable safety profile and elicited a robust immune response. METHODS We conducted a randomized, placebo-controlled, phase 3 study in 18 countries to evaluate the efficacy and safety of HZ/su in older adults (≥50 years of age), stratified according to age group (50 to 59, 60 to 69, and ≥70 years). Participants received two intramuscular doses of the vaccine or placebo 2 months apart. The primary objective was to assess the efficacy of the vaccine, as compared with placebo, in reducing the risk of herpes zoster in older adults. RESULTS A total of 15,411 participants who could be evaluated received either the vaccine (7698 participants) or placebo (7713 participants). During a mean follow-up of 3.2 years, herpes zoster was confirmed in 6 participants in the vaccine group and in 210 participants in the placebo group (incidence rate, 0.3 vs. 9.1 per 1000 person-years) in the modified vaccinated cohort. Overall vaccine efficacy against herpes zoster was 97.2% (95% confidence interval [CI], 93.7 to 99.0; P<0.001). Vaccine efficacy was between 96.6% and 97.9% for all age groups. Solicited reports of injection-site and systemic reactions within 7 days after vaccination were more frequent in the vaccine group. There were solicited or unsolicited reports of grade 3 symptoms in 17.0% of vaccine recipients and 3.2% of placebo recipients. The proportions of participants who had serious adverse events or potential immune-mediated diseases or who died were similar in the two groups. CONCLUSIONS The HZ/su vaccine significantly reduced the risk of herpes zoster in adults who were 50 years of age or older. Vaccine efficacy in adults who were 70 years of age or older was similar to that in the other two age groups. (Funded by GlaxoSmithKline Biologicals; ZOE-50 ClinicalTrials.gov number, NCT01165177.).

Efficacy of the Herpes Zoster Subunit Vaccine in Adults 70 Years of Age or Older

BACKGROUND A trial involving adults 50 years of age or older (ZOE-50) showed that the herpes zoster subunit vaccine (HZ/su) containing recombinant varicella-zoster virus glycoprotein E and the AS01B adjuvant system was associated with a risk of herpes zoster that was 97.2% lower than that associated with placebo. A second trial was performed concurrently at the same sites and examined the safety and efficacy of HZ/su in adults 70 years of age or older (ZOE-70). METHODS This randomized, placebo-controlled, phase 3 trial was conducted in 18 countries and involved adults 70 years of age or older. Participants received two doses of HZ/su or placebo (assigned in a 1:1 ratio) administered intramuscularly 2 months apart. Vaccine efficacy against herpes zoster and postherpetic neuralgia was assessed in participants from ZOE-70 and in participants pooled from ZOE-70 and ZOE-50. RESULTS In ZOE-70, 13,900 participants who could be evaluated (mean age, 75.6 years) received either HZ/su (6950 participants) or placebo (6950 participants). During a mean follow-up period of 3.7 years, herpes zoster occurred in 23 HZ/su recipients and in 223 placebo recipients (0.9 vs. 9.2 per 1000 person-years). Vaccine efficacy against herpes zoster was 89.8% (95% confidence interval [CI], 84.2 to 93.7; P<0.001) and was similar in participants 70 to 79 years of age (90.0%) and participants 80 years of age or older (89.1%). In pooled analyses of data from participants 70 years of age or older in ZOE-50 and ZOE-70 (16,596 participants), vaccine efficacy against herpes zoster was 91.3% (95% CI, 86.8 to 94.5; P<0.001), and vaccine efficacy against postherpetic neuralgia was 88.8% (95% CI, 68.7 to 97.1; P<0.001). Solicited reports of injection-site and systemic reactions within 7 days after injection were more frequent among HZ/su recipients than among placebo recipients (79.0% vs. 29.5%). Serious adverse events, potential immune-mediated diseases, and deaths occurred with similar frequencies in the two study groups. CONCLUSIONS In our trial, HZ/su was found to reduce the risks of herpes zoster and postherpetic neuralgia among adults 70 years of age or older. (Funded by GlaxoSmithKline Biologicals; ZOE-50 and ZOE-70 ClinicalTrials.gov numbers, NCT01165177 and NCT01165229 .).

Immunogenicity and Tolerability of Hepatitis A Vaccine in HIV-Infected Children

The immunogenicity and tolerability of hepatitis A virus vaccine was evaluated in a group of 32 children with human immunodeficiency virus (HIV) infection and 27 children with seroreversion. After 2 doses of vaccine, 100% of children experienced seroconversion with good toleration of the vaccine. There were no differences in variation of virus load between immunized HIV-positive children and a group of 31 nonimmunized HIV-positive children with similar characteristics.

Rubella immunization in human immunodeficiency virus type 1-infected children: cause for concern in vaccination strategies.

Background: HIV infection can have important although sometimes unexpected consequences, such as contributing to enlargement of the pool of rubella-susceptible children. Methods: At the Federal University of São Paulo, Brazil, we assessed response to rubella immunization at 15 months of age in 15 human immunodeficiency virus type 1 (HIV)-infected children, 20 seroreverted children (SR) and 18 healthy control children born to HIV-seronegative mothers (CON). Blood samples were collected before and 3 months after vaccination. All HIV-infected children had started highly active antiretroviral therapy during their first 6 months of life. Serum samples were tested with a rubella IgG enzyme-linked immunosorbent assay kit. Results: HIV children in immunologic categories 2/3 had lower rubella antibody titers (geometric mean, 33 IU/mL) than those from CON (125 IU/mL) and SR group (236 IU/mL) (Tukey, P = 0.01). Antibody values after vaccination were positively associated with CD4 T cell numbers and negatively associated with HIV viral load assessed immediately before vaccination. The percentage of children with protective antibodies after vaccination (above 10.0 IU/mL) was also significantly different among groups (Fishers exact test, P = 0.013): CON, 94%; SR, 100%; HIV category 1, 100%; HIV category 2/3, 62%. Conclusions: HIV-infected children with a preserved immune system at measles-mumps-rubella immunization can have a good response to rubella vaccine. In contrast, those in more advanced categories for HIV infection respond poorly.

Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Abstract Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010–2011. Methods. A total of 6145 children were randomly assigned at a ratio of 1:1:1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%–93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4–8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661.

Prevalence and Incidence of Respiratory Syncytial Virus and Other Respiratory Viral Infections in Children Aged 6 Months to 10 Years With Influenza-like Illness Enrolled in a Randomized Trial

In children aged 6 months to <10 years, the incidence of influenza-like illness associated with respiratory syncytial virus was 7.0 per 100 person-years. The highest burden occurred in older infants and children, which may inform vaccination strategies.

Humoral and Cellular Immune Responses to Measles and Tetanus: The Importance of Elapsed Time Since Last Exposure and the Nature of the Antigen

ObjectiveThis study aims to assess the cellular and humoral immune response pre- and post-vaccine rechallenge in healthy adults with previous exposure to measles (virus or vaccine) and different time intervals since last tetanus vaccine.MethodsHumoral immunity was tested by ELISA, and cellular immunity was tested by intracellular interferon gamma detection after in vitro stimulation with antigens.ResultsWhile cellular immunity was comparable among vaccinated individuals and those who had measles, higher antibody levels were found in those who had the disease in the past. Both antibodies and CD4+ T cell tetanus immune responses depended on elapsed time since last immunization. Following a vaccine booster, an increase in cellular immunity and antibodies was observed to both tetanus and measles. Measles humoral response was much more intense among individuals previously exposed to a wild virus.ConclusionsIn an era when natural boosters are less frequent, an immune surveillance might be necessary to investigate waning immunity as occurs for tetanus.

Respiratory viruses and influenza-like illness: Epidemiology and outcomes in children aged 6 months to 10 years in a multi-country population sample

Summary Background Better population data on respiratory viruses in children in tropical and southern hemisphere countries is needed. Methods The epidemiology of respiratory viruses among healthy children (6 months to <10 years) with influenza-like illness (ILI) was determined in a population sample derived from an influenza vaccine trial (NCT01051661) in 17 centers in eight countries (Australia, South East Asia and Latin America). Active surveillance for ILI was conducted for approximately 1 year (between February 2010 and August 2011), with PCR analysis of nasal and throat swabs. Results 6266 children were included, of whom 2421 experienced 3717 ILI episodes. Rhinovirus/enterovirus had the highest prevalence (41.5%), followed by influenza (15.8%), adenovirus (9.8%), parainfluenza and respiratory syncytial virus (RSV) (both 9.7%), coronavirus (5.6%), human metapneumovirus (5.5%) and human bocavirus (HBov) (2.0%). Corresponding incidence per 100 person-years was 29.78, 11.34, 7.03, 6.96, 6.94, 4.00, 3.98 and 1.41. Except for influenza, respiratory virus prevalence declined with age. The incidence of medically-attended ILI associated with viral infection ranged from 1.03 (HBov) to 23.69 (rhinovirus/enterovirus). The percentage of children missing school or daycare ranged from 21.4% (HBov) to 52.1% (influenza). Conclusions Active surveillance of healthy children provided evidence of respiratory illness burden associated with several viruses, with a substantial burden in older children.

A simple and cheaper in house varicella zoster virus antibody indirect ELISA

We have developed a cheaper an simple in house indirect ELISA that uses the live attenuated VZV vaccine as a coating antigen. The alternative ELISA had an agreement of 94% when compared with a commercial VZV ELISA kit. Moreover, our ELISA proved to be more reliable than the kit when assessing true negative samples. By adding a standard serum, we were able to produce results in international units per millilitre. Also, the addition of an extra step with 8M urea allowed the assessment of VZV IgG avidity without excessive costs. The cost per sample to test VZV IgG was 2.7 times cheaper with our ELISA, allowing the testing of many samples without the burden of production of VZV antigen in the laboratory.

Effectiveness of the human papillomavirus (types 6, 11, 16, and 18) vaccine in the treatment of children with recurrent respiratory papillomatosis

OBJECTIVE To evaluate whether the quadrivalent human papillomavirus (HPV) (types 6, 11, 16, and 18) vaccine influences the clinical course of juvenile-onset recurrent respiratory papillomatosis (RRP) when administered to a group of patients with this condition. METHODS Uncontrolled intervention study of patients with juvenile-onset RRP examined at the Pediatric Otorhinolaryngology Clinic, Federal University of São Paulo, where nine patients between the ages of nine and 17 received three doses of the prophylactic quadrivalent HPV vaccine (Gardasil(®)) and were followed for one year. Disease staging, intervals between relapses, intervals between surgeries, and the number of surgeries during the year prior to vaccination and during the first year after vaccination were compared. RESULTS Eight patients were infected with HPV-6 and one with HPV-11. There were no statistically significant differences in the clinical scores (p=0.083), anatomical scores (p=0.257), intervals between relapses (p=0.062), intervals between surgeries (p=0.357), or the numbers of surgeries (p=0.180) when the years before and after vaccination were compared. All patients had relapses following vaccination. CONCLUSION Patients with juvenile-onset RRP experienced a similar clinical course in the year after versus the year before vaccination with Gardasil(®).