Vaccine Allergy? Skin Testing and Challenge at a Tertiary Pediatric Hospital in Melbourne, Australia.

BACKGROUND: The rate of true vaccine allergy is unknown. Children with potential IgE-mediated adverse events following immunization (AEFI) should undergo allergy investigation that may include skin testing or challenge. Previous protocols tend to be highly conservative and often suggest invasive testing for all, a practice not evidence based, technically difficult, and unpleasant in children. It has more recently been suggested that skin testing may be restricted to those with allergic-like events within the first hour and those with a history of anaphylaxis. OBJECTIVE: We aimed to describe the outcome of vaccine skin testing and challenge in children referred to a tertiary pediatric hospital with a potential IgE-mediated AEFI. The secondary aim was to identify any significant risk factors for vaccine allergy. METHODS: A retrospective review of all children (<18 years) who underwent vaccine skin testing (skin prick testing or intradermal testing [IDT]) or challenge over a 5-year period (May 1, 2011, to April 30, 2016) at the Royal Children's Hospital Melbourne is presented. RESULTS: There were 95 admissions in 73 children. Eight percent (6 of 73) of children had confirmed vaccine allergy (positive skin testing or challenge to the index vaccination). Two had positive IDT to a suspect vaccine but challenge negative to an alternative brand vaccine. Two had negative IDT but subsequent positive challenge and two had immediate urticaria on challenge without prior skin testing. All children in the positive group either had index reaction within 15 minutes of vaccination or had history consistent with anaphylaxis. CONCLUSIONS: The vast majority of children (92%) presenting with a potential IgE-mediated AEFI are able to tolerate challenge to a suspect vaccine without reaction. We present our investigation protocol recommending skin testing in all children with anaphylaxis and challenge with a suspect vaccine if negative testing or previous nonanaphylactic potential IgE-mediated AEFI.

Update From the Advisory Committee on Immunization Practices.

The Advisory Committee on Immunization Practices (ACIP), a group of medical and public health experts, meets 3 times per year to develop recommendations for vaccine use in the United States. There are 15 voting members, and their terms are for 4 years. ACIP members and Centers for Disease Control and Prevention staff discuss the epidemiology of vaccine-preventable diseases and vaccine research, effectiveness, safety data, and clinical trial results. Representatives from the American Academy of Pediatrics (including D. W. K.) and the Pediatric Infectious Diseases Society are present as liaisons to the ACIP. In the February 2018 meeting, important votes on the use of influenza vaccine and hepatitis vaccines were held, and updates on human papillomavirus, meningococcal, and anthrax vaccines, among others, were provided.

Hepatitis A vaccine for immunosuppressed patients with rheumatoid arthritis: a prospective, open-label, multi-centre study.

BACKGROUND: Hepatitis A vaccine is the most frequently used travel vaccine, yet data are scarce about its ability to induce protection in patients with concurrent immunosuppressive treatment. We assessed the immunogenicity of this vaccine in rheumatoid arthritis (RA) patients treated with tumour necrosis factor-inhibitors (TNFi) and/or methotrexate (MTX). METHODS: Hepatitis A vaccine was administered to non-immune RA patients at 0 and 6 months. Hepatitis A virus (HAV) antibodies were assessed at 0, 1, 6, 7, 12, and 24 months with a quantitative Chemiluminescent Microparticle Immuno Assay (CMIA) for HAV-IgG. Samples from month 1, 6, and 7 were, in addition, analysed with a microparticle EIA (MEIA) for anti-HAV IgM + IgG. RESULTS: The final study population consisted of 53 patients treated with TNFi (n = 15), TNFi + MTX (n = 21) or MTX (n = 17). One and six months after the first dose, 10% and 33% of the patients had attained seroprotection. One and six months after the second dose 83% and 72% were seroprotected. At month 24, 86% of the vaccinees showed protective levels. CONCLUSIONS: Two doses of hepatitis A vaccine at a 6-month interval provided protection for most immunosuppressed RA patients. A single dose does not seem to afford sufficient protection to this group of patients.

Vaccinating HIV patients: focus on human papillomavirus and herpes zoster vaccines.

Vaccination has been one of our most powerful tools to decrease morbidity and mortality from infectious diseases in the last century. It is critical to understand the evolving safety and efficacy data for vaccines in HIV-infected individuals as the number of people living with HIV in the United States and globally continues to increase. The quadrivalent human papillomavirus vaccine and the herpes zoster vaccine are newly licensed in the general population, and several studies have recently been published on the safety and efficacy of these vaccines in HIV populations. This manuscript reviews recent data for the vaccines most commonly administered in HIV patients and incorporates these data into our body of knowledge about the safety and efficacy of vaccines in this population. In addition, patient factors that predict response for each vaccine are discussed. Given the great burden of human papillomavirus and herpes zoster in HIV patients, we discuss the benefits and the challenges of vaccinating HIV patients with the human papillomavirus and herpes zoster vaccines. This review provides information that clinicians need to make real-time decisions in the absence of large-scale trials in the HIV population.

Randomized trial: immunogenicity and safety of coadministered human papillomavirus-16/18 AS04-adjuvanted vaccine and combined hepatitis A and B vaccine in girls.

PURPOSE: This randomized, open, controlled, multicenter study (110886/NCT00578227) evaluated human papillomavirus (HPV)-16/18 AS04-adjuvanted vaccine (HPV-16/18 vaccine) coadministered with inactivated hepatitis A and B (HAB) vaccine. Coprimary objectives were to demonstrate noninferiority of hepatitis A, hepatitis B, and HPV-16/18 immune responses at month 7 when vaccines were coadministered, compared with the same vaccines administered alone. METHODS: Healthy girls (9-15 years) were age-stratified (9, 10-12, and 13-15 years) and randomized to receive HPV (n = 270), HAB (n = 271), or HPV + HAB (n = 272). Vaccines were administered at months 0, 1, and 6. Immunogenicity was evaluated at months 0 and 7. RESULTS: The hepatitis A immune response was noninferior for HPV + HAB, versus HAB, for seroconversion rates (100% in each group) and geometric mean antibody titers (GMTs) (95% CI) (4,504.2 [3,993.0-5,080.8] and 5,288.4 [4,713.3-5,933.7] mIU/mL, respectively). The hepatitis B immune response was noninferior for HPV + HAB, versus HAB, for anti-HBs seroprotection rates (98.3% and 100%); GMTs were 3,136.5 [2,436.0-4,038.4] and 5,646.5 [4,481.3-7,114.6] mIU/mL, respectively. The HPV-16/18 immune response was noninferior for HPV + HAB, versus HPV, for seroconversion rates (99.6% and 100% for both antigens) and GMTs (22,993.5 [20,093.4-26,312.0] and 26,981.9 [23,909.5-30,449.1] EL.U/mL for HPV-16; 8,671.2 [7,651.7-9,826.6] and 11,182.7 [9,924.8-12,600.1] EL.U/mL for HPV-18, respectively). No subject withdrew because of adverse events. No vaccine-related serious adverse events were reported. Immune responses and reactogenicity were similar in girls aged 9 years compared with the entire study population. CONCLUSIONS: Results support coadministration of HPV-16/18 vaccine with HAB vaccine in girls aged 9-15 years. The HPV-16/18 vaccine was immunogenic and generally well tolerated in 9-year-old girls.

National Vaccine Injury Compensation Program: revisions to the vaccine injury table. Final rule.

On September 13, 2010, the Secretary of Health and Human Services (the Secretary) published in the Federal Register a Notice of Proposed Rulemaking (NPRM) proposing changes to the regulations governing the National Vaccine Injury Compensation Program (VICP). Specifically, the Secretary proposed revisions to the Vaccine Injury Table (Table) to create distinct listings for hepatitis A, trivalent influenza, meningococcal, and human papillomavirus vaccines. The Secretary is now making this amendment to the Table by final rule; it is technical in nature. The four categories of vaccines described in this final rule are already covered vaccines under the VICP (starting in 2004) and are currently listed in a placeholder category (box XIII) in the Table. This final rule will list these vaccines as separate categories on the Table, with no associated injuries noted at this time, in order to help the public identify clearly that these vaccines are covered by the VICP. The changes implemented here are authorized by section 2114(e) of the Public Health Service Act (the Act).

Evaluation of immune response to hepatitis A vaccination and vaccine safety in juvenile idiopathic arthritis.

BACKGROUND: Autoimmune mechanisms and drugs used in treatment increase the risk of liver disease in patients with juvenile idiopathic arthritis (JIA) and hepatitis A virus (HAV) vaccination is important, especially in intermediate-endemicity areas like Turkey. In our study, we aimed to evaluate the immune response to hepatitis A vaccine and vaccine safety in children with JIA. METHODS: This study was carried out in our hospital's Pediatric Rheumatology outpatient clinic and Healthy Child clinic between the years 2003 and 2008. The study group consisted of 47 children with JIA (23 male and 24 female) diagnosed according to International League of Associations for Rheumatology diagnostic criteria. The control group consisted of 67 healthy children (31 female, 36 male) who did not have a history of hepatitis A infection or vaccination. Both groups were vaccinated with two doses of hepatitis A vaccine at 6-month intervals. Anti-HAV IgG >80 MIU was accepted as positive response. RESULTS: There was no significant difference between the groups in terms of age and sex. None of the patients with JIA had fever, clinical worsening, or disease activation after vaccination. Anti-HAV IgG positivity rate was significantly higher in the control group (p < 0.05). Anti-HAV IgG was negative in only four cases, and they were all male patients with systemic JIA who had active disease under anti-tumor necrosis factor treatment. CONCLUSION: Hepatitis A vaccine was safe in patients with JIA, and response to vaccine did not differ between healthy children and patients with JIA except for children with active systemic JIA receiving anti-tumor necrosis factor alpha drugs.

Neuromuscular complications of hepatitis A virus infection and vaccines.

The hepatitis A virus (HAV) infects millions of people worldwide every year. Case histories report on various acute neuropathy syndromes in the context of acute HAV infection, but any causal link has not been established. Epidemiological data also cast doubt on the importance of HAV as a trigger for Guillain-Barré syndrome. The virtual absence of a chronic HAV-infected state likely explains the rare occurrence of extrahepatic immune-mediated diseases, including an absence of chronic autoimmune neuromuscular disorders. Several vaccines against HAV provide effective protection against natural infection. Isolated case histories report on an unconvincing association between HAV vaccination and neuropathy. Medical and epidemiological data show insufficient evidence to support a causal relationship between HAV vaccines and neuropathy syndromes. Aluminum hydroxide, a HAV vaccine adjuvant, is considered a trigger of the macrophagic myofasciitis syndrome. This review concludes that it seems unnecessary to routinely consider HAV infection or vaccination as triggers of neuromuscular diseases.

Immunogenecity of hepatitis A vaccine in pediatric patients with inflammatory bowel disease.

BACKGROUND: There are only a few studies on immune response to routine vaccinations in children with inflammatory bowel disease (IBD), despite a strong need for this kind of study. The aim of the study was to evaluate the immunogenicity of an inactivated hepatitis A vaccine (HAV) in IBD pediatric patients compared with healthy controls. METHODS: This was an open, prospective, and controlled study on anti-HAV-negative children and adolescents age 2-18 years with IBD. HAV using 720 enzyme-linked immunosorbent assay (ELISA) units were administered at 0 months and at 6-12 months. Seroconversion and geometric mean titers were measured after each vaccine dose. The evidence of local and systemic adverse effects for 3 days after the first and second dose of vaccine was registered. RESULTS: A total of 134 subjects (66 patients and 68 controls) completed the whole study course consisting of two doses of vaccine and six serum samples. There was no significant difference in the rate of seroconversion between IBD patients and controls when measured after the second dose of vaccine (97% versus 100%, P = 0.2407), but the rate was significantly lower in the IBD group when measured after the first dose (39% versus 64%, P = 0.00001). The mean geometric titers were statistically significantly lower in the IBD group than in the control group at all of the measured timepoints. There were no serious adverse events related to HAV during the study. CONCLUSIONS: HAV is both immunogenic and safe in pediatric patients with IBD.

Vaccination with a human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine in Korean girls aged 10-14 years.

The human papillomavirus (HPV)-16/18 AS04-adjuvanted cervical cancer vaccine has been demonstrated to be highly efficacious and immunogenic with a favorable safety profile. This study assessed the immunogenicity and safety of the HPV-16/18 AS04-adjuvanted vaccine in healthy Korean girls aged 10-14 yr. This multi-center, observer-blind trial randomly assigned 321 healthy girls to receive three doses (0, 1, 6-month schedule) of HPV-16/18 AS04-adjuvanted vaccine or hepatitis A vaccine. Immunogenicity against vaccine antigens was assessed one month post-Dose 3. Solicited and unsolicited adverse events (AEs) and serious AEs (SAEs) were recorded. In the according-to-protocol analysis, all initially seronegative subjects vaccinated with the HPV-16/18 AS04-adjuvanted vaccine had seroconverted at Month 7, with a peak geometric mean titer (GMT) that was 600-fold higher than the natural infection titer of 29.8 EU/mL for HPV-16 and a peak GMT that was 400-fold higher than the natural infection titer of 22.6 EU/mL for HPV-18. The vaccine was well tolerated with no increase in reactogenicity with subsequent doses and no reports of vaccine-related SAEs. In conclusion, the HPV-16/18 AS04-adjuvanted vaccine is shown to be highly immunogenic and generally well-tolerated in Korean girls aged 10-14 yr.

Vaccination as a triggering event for autoimmune hepatitis.

The pathogenesis of autoimmune hepatitis entails complex interactions between triggering factors, autoantigens, genetic predisposition, and immunoregulatory networks. Implicated triggering factors are numerous and include toxins, medications, and infectious agents. In this article, we present a unique case of a 31-year-old woman with severe autoimmune hepatitis apparently abruptly triggered by vaccination. All evidence suggests this was an idiosyncratic response to either hepatitis A or yellow fever vaccination.

Vaccine adjuvant systems containing monophosphoryl lipid A and QS21 induce strong and persistent humoral and T cell responses against hepatitis B surface antigen in healthy adult volunteers.

A randomised, double-blind study assessing the potential of four adjuvants in combination with recombinant hepatitis B surface antigen has been conducted to evaluate humoral and cell-mediated immune responses in healthy adults after three vaccine doses at months 0, 1 and 10. Three Adjuvant Systems (AS) contained 3-O-desacyl-4'-monophosphoryl lipid A (MPL) and QS21, formulated either with an oil-in-water emulsion (AS02B and AS02V) or with liposomes (AS01B). The fourth adjuvant was CpG oligonucleotide. High levels of antibodies were induced by all adjuvants, whereas cell-mediated immune responses, including cytolytic T cells and strong and persistent CD4(+) T cell response were mainly observed with the three MPL/QS21-containing Adjuvant Systems. The CD4(+) T cell response was characterised in vitro by vigorous lymphoproliferation, high IFN-gamma and moderate IL-5 production. Antigen-specific T cell immune response was further confirmed ex vivo by detection of IL-2- and IFN-gamma-producing CD4(+) T cells, and in vivo by measuring increased levels of IFN-gamma in the serum and delayed-type hypersensitivity (DTH) responses. The CpG adjuvanted vaccine induced consistently lower immune responses for all parameters. All vaccine adjuvants were shown to be safe with acceptable reactogenicity profiles. The majority of subjects reported local reactions at the injection site after vaccination while general reactions were recorded less frequently. No vaccine-related serious adverse event was reported. Importantly, no increase in markers of auto-immunity and allergy was detected over the whole study course. In conclusion, the Adjuvant Systems containing MPL/QS21, in combination with hepatitis B surface antigen, induced very strong humoral and cellular immune responses in healthy adults. The AS01B-adjuvanted vaccine induced the strongest and most durable specific cellular immune responses after two doses. These Adjuvant Systems, when added to recombinant protein antigens, can be fundamental to develop effective prophylactic vaccines against complex pathogens, e.g. malaria, HIV infection and tuberculosis, and for special target populations such as subjects with an impaired immune response, due to age or medical conditions.

[Antiviral immunization of immunocompromised adults, literature review]. / Vaccination antivirale des adultes immunodéprimés, revue de la littérature.

PURPOSE: Immunization, by preventing infections, has a major interest for the immunocompromised subjects. The aim of this article is to make a point on data concerning efficacy (in terms of immunogenicity) and safety of viral vaccines available in France and to synthesize existing guidelines for four groups of patients: solid organ and hematopoietic stem cell transplant recipients, HIV infected persons and patients treated by immunosuppressive drugs for a systemic disease. CURRENT KNOWLEDGE AND KEY POINTS: Available data about vaccines immunogenicity and safety for immunocompromised adults are rare. However, those data indicate that, when immunization contraindications and recommendations are applied, vaccines remain well tolerated and most of the time immunogenic, even if the percentage of responders is lower compared to non immunocompromised persons. Still, the specific guidelines that have been elaborated for immunization of immunocompromised adults are imprecise and incomplete, emphasizing a lack of data about this topic. FUTURE PROSPECTS: Clinical studies remain necessary to precise vaccines immunogenicity and safety for immunocompromised adults. In the meantime, a harmonization of immunization practices for immunocompromised adults should be proposed, so as to help practitioners to succeed a better immunization coverage for these patients.

Hepatitis A vaccine associated with autoimmune hepatitis.

To describe a case of probable relapsing autoimmune hepatitis associated with vaccination against hepatitis A virus (HAV). A case report and review of literature were written concerning autoimmune hepatitis in association with hepatitis A and other hepatotropic viruses. Soon after the administration of formalin-inactivated hepatitis A vaccine, a man who had recently recovered from an uncharacterized but self-limiting hepatitic illness, experienced a severe deterioration (AST 1687 U/L, INR 1.4). Anti-nuclear antibodies were detectable, and liver biopsy was compatible with autoimmune hepatitis. The observation supports the role of HAV as a trigger of autoimmune hepatitis. Studies in helper T-cell activity and antibody expression against hepatic proteins in the context of hepatitis A infection are summarized, and the concept of molecular mimicry with regard to other forms of viral hepatitis and autoimmunity is briefly explored.

Reduced-dose intradermal vaccination against hepatitis A with an aluminum-free vaccine is immunogenic and can lower costs.

A reduced dose (0.1 mL) of intradermal hepatitis A virus (HAV) vaccine could facilitate the control of hepatitis A in countries of endemicity. All study subjects receiving an aluminum-free HAV vaccine intradermally were seroprotected 28 days after vaccination (anti-HAV titer, > or =10 mIU/mL). Seroprotection rates decreased to 80.8% at 12 months but returned to 100%, with titers increasing 28-fold, after receipt of a booster vaccination.

Macrophagic myofasciitis associated with vaccine-derived aluminium.

Macrophagic myofasciitis is characterised by sheets of macrophages in striated muscle, a few lymphocytes and inconspicuous muscle fibre damage. It is due to aluminium contained in vaccines, and is localised to the inoculation site. We report the first Australian case, detected incidentally when investigating a raised serum creatine kinase level.

Vaccination-induced cutaneous pseudolymphoma.

BACKGROUND: Although mild early cutaneous transient reactions to vaccinations are common, late-onset chronic lesions have been scarcely reported. We report herein a series of 9 patients presenting with cutaneous and subcutaneous pseudolymphoma. OBSERVATIONS: Nine patients presenting with late-onset, chronic skin lesions occurring at the site of antihepatitis B (8 cases) and antihepatitis A (one case) vaccination were reported. Histopathologic and immunohistochemic studies, and molecular analysis of clonality of skin biopsy specimens, were performed. Furthermore, the presence of vaccine products was investigated in skin lesions by using histochemical, microanalytic, and electronic microscopy techniques. RESULTS: Histopathologic studies showed dermal and hypodermal lymphocytic follicular infiltrates with germinal center formation. The center of follicles was mostly composed of B cells without atypia, whereas CD4+ T cells were predominant at the periphery. Molecular analysis of clonality revealed a polyclonal pattern of B-cell and T-cell subsets. Aluminium deposits were evidenced in all cases by using histochemical staining in all cases, and by microanalysis and ultrastructural studies in one case. Associated manifestations were vitiligo (one case) and chronic fatigue with myalgia (two cases). CONCLUSION: Cutaneous lymphoid hyperplasia is a potential adverse effect of vaccinations including aluminium hydroxide as an adjuvant. Further prospective studies are warranted to evaluate the incidence of this complication in the immunized population.

Interchangeability and tolerability of a virosomal and an aluminum-adsorbed hepatitis A vaccine.

The interchangeability of virosomal (Epaxal) and aluminum-adsorbed (Havrix 1440) hepatitis A virus (HAV) vaccines was studied in 111 healthy adults who were vaccinated in a randomized, single-blind, crossover clinical trial. Anti-HAV antibody titers were measured at days 0 (first dose), 14, and 28, and months 3, 6, 12 (second dose), 13, 24, 36, 48, 60 and 72. Most subjects (>95%) had sero-converted 14 days after the first dose of either vaccine. The second dose with either vaccine induced a high antibody response in all vaccines, irrespective of the type of vaccine administered as the first dose. Although both vaccines were well tolerated, the incidence of local adverse events (in particular pain) was significantly lower in subjects receiving the virosomal vaccine. Six-year follow-up data did not reveal any significant differences between the vaccination groups.

Immunogenicity of booster vaccination with a virosomal hepatitis A vaccine after primary immunization with an aluminum-adsorbed hepatitis A vaccine.

BACKGROUND: Increasing numbers of individuals are traveling to areas of high hepatitis A endemicity and require immunization against the hepatitis A virus (HAV). The option of using a virosomal, aluminum-free, HAV vaccine (Epaxal) for booster immunization following primary vaccination with an aluminum-adsorbed vaccine has been assessed. METHODS: In total, 142 healthy subjects, 79 men and 63 women, aged 12 to 72 years, were injected intramuscularly with a booster dose of Epaxal (0.5 mL containing < or =500 RIA units of HAV antigen) 6 to 24 months after primary vaccination with Havrix (0.5 or 1.0 mL containing 720 or 1440 ELISA units of HAV antigen, respectively, adsorbed onto aluminum hydroxide). Anti-HAV antibody titers were measured on days 0 and 28 by an enzyme immunoassay. Adverse events were recorded for 1 month postinjection. RESULTS: Overall, 98/118 subjects (83%) with no serologic evidence of past HAV infection were still seroprotected at enrolment (anti-HAV antibody titer < or = 20 mIU/mL). The seroprotection rate was 87% in those primed with Havrix 1440 6 to 12 months earlier (n=93) and 60% in those primed < or =12 months before enrolment (n=20, mean 16 months). The geometric mean anti-HAV antibody titer increased from 65 mIU/mL at day 0 to 1,722 mIU/mL at day 28 after a single booster dose with Epaxal in evaluable subjects who were primarily vaccinated with either a single dose of Havrix 1440 (n=111) or two separate doses of Havrix 720 (n=4). All subjects were seroprotected at day 28, and 98% showed at least a four-fold increase in anti-HAV antibody titer. Epaxal was well tolerated and no serious adverse events were reported. At day 28, the tolerability of the vaccination was judged as either "very good" or "good" by 96% of vaccinees and by all investigators. CONCLUSION: Epaxal can be successfully used to boost immunization following primary vaccination with an aluminum-adsorbed vaccine, and is well tolerated.