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In ovo vaccination of chicken embryos with experimental Newcastle disease and avian influenza oil-emulsion vaccines.

Inactivated oil-emulsion (OE) Newcastle disease (ND) and avian influenza (AI) vaccines were injected into 18-day-old white rock (WR) and white leghorn (WL) chicken embryos to evaluate their immunologic efficacy and their effects on hatchability. Embryonating eggs were inoculated at 1.5 inches depth with various vaccine volumes and antigen concentrations. Serum hemagglutination-inhibition (HI) titers were first detected in chickens at 2 wk posthatch. Protection against morbidity and mortality was demonstrated in all of 10 chickens vaccinated as embryos and challenged with viscerotropic velogenic ND virus at 53 days of age and also in all of eight in ovo- vaccinated chickens challenged with highly pathogenic AI virus at 34 days of age. All of five unvaccinated control chickens for each respective ND- and AI-vaccinated group died. In pooled groups from successive hatches, the hatchability of WR or WL embryos injected with 100 microliters of vaccine was not significantly different (P > 0.05) from unvaccinated hatchmate controls when needle gauges of 22, 20, and 18 were used. Seroconversion rates of chickens vaccinated as embryos ranged from 27% to 100% with ND vaccination and 85% to 100% for AI vaccination. For ND, geometric mean HI titers of chickens per vaccine group ranged from 11 to 733, and in pooled groups, the range was 49 to 531. Titers for AI vaccine groups ranged from 156 to 1178. This study demonstrated that acceptable hatchability, seroconversion rates, and protective immunity can be attained with in ovo inoculation of ND or AI OE vaccines if the vaccines are prepared with sufficient antigen and administered properly.

Animals↗

Simultaneous administration of a diphtheria and tetanus toxoids and acellular pertussis vaccine with measles-mumps-rubella and oral poliovirus vaccines.

OBJECTIVE: To compare the safety and immunogenicity of Lederle Laboratories' (Pearl River, NY) diphtheria and tetanus toxoids and acellular pertussis (DTaP) vaccine with diphtheria and tetanus toxoids and whole-cell pertussis (DTwP) vaccine when administered simultaneously with measles-mumps-rubella (MMR) vaccine and trivalent oral poliovirus (OPV) vaccine at 15 to 16 months of age. DESIGN: Randomized and double-blind. SETTING: Two general pediatric practices. PARTICIPANTS: Ninety-seven infants, aged 15 to 16 months, who had received three previous DTwP immunizations. SELECTION PROCEDURES AND INTERVENTIONS: Healthy children received the DTaP or DTwP vaccine. Infants received the MMR vaccine at a separate site and the OPV vaccine concurrently. Blood was obtained on day 0 and at 6 weeks. Adverse events were recorded by parents at specified times after immunization. MEASUREMENTS/RESULTS: Within 3 days of immunization, DTaP vaccine recipients had less fever, drowsiness, and irritability (P = .01, .04, .01, respectively). They also experienced less tenderness, erythema, and induration (.001, .001, and .002, respectively). There was no difference in the frequency of adverse reactions 6 to 14 days after immunization. Enzyme-linked immunosorbent assays were used to determine all antibody values. Antibody responses to filamentous hemagglutinin and pertussis toxoid were significantly greater in the DTaP group (P = .0001 and .02, respectively). Immune responses to the other measured antigens were similar. CONCLUSIONS: Simultaneous administration of the Lederle DTaP with MMR and OPV vaccines did not interfere with antibody response to pertussis antigens measured or measles, mumps, or rubella viruses and was associated with fewer local and systemic adverse events during the first 3 days following immunization when compared with the simultaneous administration of the DTwP, OPV, and MMR vaccines. We conclude that the DTaP vaccine can be administered at 15 months of age concurrently with the MMR and OPV vaccines.

Anorexia↗

Levels of circulating regulatory CD4+CD25+ T cells are decreased in breast cancer patients after vaccination with a HER2/neu peptide (E75) and GM-CSF vaccine.

PURPOSE: We are conducting clinical trials in breast cancer (BrCa) patients to test the HER2/neu peptide vaccine (E75). We have investigated the impact of this vaccine on circulating levels of regulatory T cells (Treg) and the resulting effects on antitumor responses. EXPERIMENTAL DESIGN: Twenty-two blood samples from healthy individuals and from 22 BrCa patients including pre- and post-vaccination samples from seven vaccinated HLA-A2+ patients were stained for CD4, CD25, and CD69 as well as CD8 and E75:HLA-A2 Ig dimer and quantified by flow cytometry. Cytotoxic activity against HER2/neu+ tumors was measured by 51Cr-release. Serum from BrCa patients and normal subjects were analyzed for TGF-beta levels. RESULTS: BrCa patients have a greater percentage of circulating Treg (CD4+CD25+, 4.45% versus 2.96%; p=0.007) than normal subjects. HLA-A2+ BrCa patients had more Treg compared to the HLA-A2- BrCa patients (CD4+CD25+, 5.63% versus 3.28%; p=0.001). E75 vaccination increased circulating activated CD4+ T cells post-vaccination (CD4+CD69+, 1.23 versus 3.81%; p=0.03). However, T(reg) were significantly reduced after vaccination (CD4+CD25+, 5.31-1.81%; p<0.0001). Furthermore, activated Treg also decreased (CD4+CD25+CD69+, 0.23% versus 0.08%; p=0.06). Importantly, post-vaccination decreases in Treg were temporally associated with increased E75 vaccine-specific CD8+ T cells and corresponding HER2/neu+ tumor cytotoxicity. Serum TGF-beta levels were significantly elevated in BrCa patients compared to normals (3548 pg/ml versus 1007 pg/ml; p=0.007). Four of seven vaccinated patients showed decreased serum TGF-beta levels post-vaccination. CONCLUSIONS: Treg, are increased in BrCa patients along with serum levels of TGF-beta. E75 vaccination resulted in CD4+ recruitment but was associated with a significant decrease in circulating Treg and TGF-beta levels in the majority of the vaccinated patients. Successful cancer vaccination strategies may require the alteration of complex immune interactions.

Antigens, CD↗

Effect of nationwide vaccination of 3-month-old infants in The Netherlands with conjugate Haemophilus influenzae type b vaccine: high efficacy and lack of herd immunity.

OBJECTIVE: The effect of nationwide vaccination in The Netherlands with conjugate Haemophilus influenzae type b vaccine on the incidence of H. influenzae meningitis was assessed in the first 3 years after the introduction of vaccination to the birth cohort at 3 months of age. STUDY DESIGN: Children in The Netherlands born after April 1, 1993, were vaccinated at the age of 3, 4, 5, and 11 months. Children older than 3 months at the inception of the H. influenzae type b vaccination program were not immunized. The number of cases among the vaccine cohort was compared with the number in a historical control group of children born in the period April 1, 1990, and April 1, 1993. RESULTS: The total number of patients with meningitis caused by H. influenzae type b reached a low, but constant level, that was expected for absence of herd immunity. Among children in the vaccine era group 22 cases occurred, whereas among the historical control group (prevaccine era) 342 cases were found. In the vaccine era cohort, 2 patients with H. influenzae type b meningitis had been vaccinated three times, 13 received one or no vaccine dose because of their age, and 7 were not vaccinated for religious or logistic reasons. The number of cases among nonvaccinated children older than 3 years and the number of H. influenzae meningitis cases caused by strains other than type b did not change. CONCLUSIONS: Conjugate H. influenzae type b vaccine prevents H. influenzae type b meningitis very effectively (99.4%) in children vaccinated twice or more. To reach rapid prevention of all H. influenzae type b disease simultaneous introduction of H. influenzae type b vaccination of children at various ages is recommended.

Cohort Studies↗

Antibody responses and HIV-1 viral load in HIV-1-seropositive subjects immunised with either the MF59-adjuvanted influenza vaccine or a conventional non-adjuvanted subunit vaccine during highly active antiretroviral therapy.

OBJECTIVE: To study immunological and virological parameters in HIV-1-seropositive adults treated with highly active antiretroviral therapy (HAART) for at least 7 months after immunisation with MF59-adjuvanted (FLUAD, Chiron, Siena, Italy) or with non-adjuvanted (AGRIPPAL, Chiron) trivalent influenza vaccine. DESIGN: Blood samples, collected before and after vaccination, were analysed for the presence of antibodies against the vaccine antigens, for number of CD4+ T lymphocytes and HIV-1 RNA levels. RESULTS: Forty-four volunteers received FLUAD and 40 AGRIPPAL influenza vaccine. Thirty days after vaccination both adjuvanted and non-adjuvanted vaccines induced significant increases of anti-influenza virus antibodies. However, antibody titres found in volunteers receiving adjuvanted vaccine were in general significantly higher when compared with those found in the non-adjuvanted vaccine group. The requirements of the European Commission of influenza vaccine for a non-elderly adult population were always met by recipients of the adjuvanted vaccine, even in those with the lowest CD4+ cell counts (<200 cells/mmc). The subjects receiving the non-adjuvanted vaccine failed to met these requirements. The CD4+ T lymphocytes and plasma HIV-1 RNA levels remained stable in the long term, both in people receiving adjuvanted or non-adjuvanted vaccine. CONCLUSION: MF59-adjuvanted influenza induced a significant higher immune responses as compared with conventional vaccine in HIV-seropositive HAART-treated patients. Both vaccines were safe regarding HIV RNA viral replication and loss of CD4+ T lymphocytes.

Adjuvants, Immunologic↗

Effects of repeated annual influenza vaccination on vaccine sero-response in young and elderly adults.

Three cohort studies in adults were performed during the period from 1986 to 1989. Eight hundred and eighty-four subjects were, one or more times, immunized with influenza vaccines, and pre- and post-vaccination antibody titres were determined by hemagglutination inhibition tests. One thousand and one hundred and nineteen vaccination events in 681 subjects could be analysed by a comparison, per trial and per influenza (sub)type, between groups with and without influenza vaccination in previous years. Effect size, odds ratio and protection rate difference, were used as effect measures. Subjects with previous vaccination showed higher pre-vaccination antibody than those without. The average change of the post-vaccination proportion of subjects with high antibody titre value to previous vaccination, was +9.4% (95% CI: +5.3 to 13.6%) for A-H3N2 vaccine components, -2.1% (-8.1 to 3.9%, not significant) for A-H1N1 and -10.6% (-16.5% to -4.8%) for B. In a linear regression model, pre-vaccination titres and the status of previous vaccination were identified as factors significantly influencing post-vaccination titres. These findings are discussed in the context of a short review of the literature. It is concluded that the status of previous vaccination should always be addressed as an independent factor in serological vaccination studies.

Adult↗

Influenza vaccination of staff in aged care facilities in the ACT: how can we improve the uptake of influenza vaccine?

OBJECTIVE: To examine the self-reported uptake of influenza vaccine by staff in residential aged care facilities in the Australian Capital Territory (ACT), and the factors influencing vaccine uptake by staff. METHODS: Two confidential cross-sectional surveys were conducted in all (n = 19) residential aged care facilities in the ACT in June 2000. An interview with directors of each facility collected information on the institutional policy and practices for influenza vaccination. An anonymous postal survey of staff collected information on self-reported influenza vaccination status and staff awareness and attitudes to the vaccination. RESULTS: All directors were interviewed (n = 19) and 50% of staff questionnaires (n = 587) were completed. Of respondents, 28% reported receiving influenza vaccine for the 2000 influenza season. Uptake of the vaccine was associated with particular policies and practices of facilities such as: organisation of vaccination for staff (OR 2.52, CI 1.38-4.59, p < 0.001); provision of reminders to staff (OR 2.73, CI 1.70-4.06, p < 0.001); and provision of information on the need for vaccination (OR 1.94, CI 1.03-3.67, p < 0.001). Other factors significantly associated with influenza vaccine uptake included: previous uptake of the vaccine (OR 52.2, CI 35.2-77.4, p < 0.001), vaccination arranged by the workplace (OR 4.02, CI 2.66-6.07, p < 0.001), and awareness of recommendations for staff employed in aged care facilities (OR 3.66, CI 2.28-5.85, p < 0.001). The main reasons given for not receiving the vaccine were the belief that it had significant side effects (42%, n = 146), and concerns about its effectiveness (32%, n = 109). CONCLUSIONS: This study identified a number of factors that can be incorporated into strategies and programs to improve uptake of influenza vaccine by staff in residential aged care facilities.

Adult↗

[Childhood vaccinations anno 2004. I. Effectiveness and acceptance of the Dutch National Vaccination Programme].

Vaccinations are the most effective measures in public health. In the Netherlands after the second world war the morbidity and mortality of infectious diseases were a great problem. Nowadays these diseases are gone or reduced at a minimal level and for the greater part under control. The Dutch National Vaccination Programme aims at 10 infectious diseases. In the Netherlands there has always been a relatively small group of religious people who live together and reject vaccinations. Since the start of the vaccination programme in this group several small epidemics of poliomyelitis and measles have been observed. The other dispersed living non-vaccinated people are protected by herd-immunity, as long as the vaccination coverage is above 90%. During recent years an increasing number of people have doubts over the use and safety of vaccinations. There is a worldwide anti-vaccination movement, in the Netherlands represented by the 'Nederlandse Vereniging Kritisch Prikken'. The finding that there is now a greater spread of areas with a low or insufficient vaccination coverage, is cause for concern because experiences in several countries have shown that infectious diseases with all complications will recur when the vaccination percentage decreases. There is no scientific support for the hypothesis that vaccinations overwhelm or weaken the immune system of infants and there is no objection to start with vaccination at the age of two months. Anthroposofic and homeopathic arguments are neither scientifically, nor practically supported. Good promotion and education about the vaccination programme is of great importance and can be improved. Parents should make decisions based on good, objective information. Possible risks and side effects of vaccination should not be concealed.

Child↗

[Childhood vaccinations anno 2004. II. The real and presumed side effects of vaccination].

Vaccinations protect to a high degree against infectious diseases, but may cause side effects. In the Netherlands since 1962 the adverse events following immunizations are registered and analysed by the National Institute of Health and Environment (RIVM). Since 1983 a permanent Committee of the Dutch Health Council reviews adverse events reported to the RIVM. With the so-called killed vaccines the side effects are mainly local (redness, swelling, pain) or general (fever, listlessness, irritability, sleep and eating problems). They are seen mainly after DPT-IPV vaccination against diphtheria, pertussis, tetanus and poliomyelitis. Some side effects occur rarely (collapse reactions, discoloured legs, persistent screaming and convulsions) and very rarely serious neurological events are reported. After MMR vaccination against measles, mumps and rubella, cases of arthritis, thrombocytopenia and ataxia are reported sporadically. Usually, they have a spontaneous recovery. During recent years a scala of diseases or symptoms have been associated with vaccination (presumed side effects). Careful and extensive investigations have shown that such hypotheses could not be supported. Examples are allergic diseases as asthma, diabetes mellitus, multiple sclerosis (after hepatitis B vaccination), autism and inflammatory bowel disease (after MMR vaccination) and sudden infant death syndrome. The total number of cases where at least a possible relation between side effects and vaccination is observed--apart from local reactions and moderate general symptoms--is very rare (about 0.25 per 1000 vaccinations) and does not balance the benefits from vaccination. There appears increasing doubt about the use and safety of vaccinations. More research is needed about the motives of people to choose for and against vaccination. The education about vaccination for parents and professionals who are involved with vaccination has to be improved. Internet can play an important role.

Child↗

Comparative immunogenecity of foot and mouth disease virus antigens in FMD-haemorrhagic septicaemia combined vaccine and FMD vaccine alone in buffalo calves.

Humoral immune response was evaluated by monitoring the serum antibody titres and virus specific IgM titres against Foot and Mouth Disease (FMD) virus antigens in serum samples obtained from different groups of calves inoculated with combined vaccine or FMD vaccine alone, on 0, 7, 14, 21, 28, 42 and 56 days post-vaccination (DPV). The cellular immune response was monitored by MTT based lymphoproliferation in peripheral blood mononuclear cell cultures. Higher liquid phase blocking (LPB) ELISA antibody titres were observed in calves receiving combined vaccine as compared to calves immunized with FMD vaccine alone with the peak titres in both the groups obtained on 21 days post-vaccination. However, the virus specific IgM titres were significantly higher in group of calves inoculated with combined vaccine than FMD vaccine alone. The lymphoproliferative responses against FMDV types O, A22 and Asia 1 in the groups receiving combined vaccine and FMD vaccine alone started increasing gradually after day 14 and reached peak levels on 28 DPV followed by a gradual decline subsequently. The group receiving combined vaccine showed higher proliferative responses on in vitro stimulation with FMD virus type O, whereas, with FMD virus type Asia 1, the responses were significantly higher on 14 and 21 DPV as compared to the group immunized with FMD vaccine alone. However, in the group receiving combined vaccine, the responses on in vitro stimulation with FMD virus type A22 were significantly higher than FMD vaccine alone group on all DPV except on 42 DPV.

Animals↗

Factors affecting the efficacy of live poliovirus vaccine in warm climates. Efficacy of type 1 Sabin vaccine administered together with antihuman gamma-globulin horse serum to breast-fed and artificially fed infants in Uganda.

A virologically controlled field trial was conducted with live monovalent type 1 poliovirus vaccine in children aged 3-30 months living in a rural area of Uganda, in an attempt to find out the reason for the poor efficacy of such vaccine often observed in countries with a warm climate. Groups of breast-fed and of artificially fed infants received the vaccine orally, either alone or mixed with horse serum prepared against partly purified human gamma-globulin. Irrespective of the diet, the "take rate"-measured by the rates of vaccine virus excretion and of antibody conversion-was found to be poor when the vaccine was given alone but satisfactory when it was given together with the horse antiserum. However, the extent and duration of vaccine virus multiplication in the intestinal tract proved to be limited and the mean antibody level elicited by the vaccination, irrespective of the schedule of vaccine administration, was low. These results, besides indicating that breast-feeding does not influence the efficacy of vaccination in the age groups studied, revealed the presence of an inhibitor in the alimentary tract. This inhibitor acts against the multiplication of vaccine virus, which may be blocked by antibodies in the horse antiserum for a limited period at the time of vaccination. Interference between the enteroviruses and the vaccine strain was also found to be responsible for decreasing the efficacy of vaccination, though its role was secondary to that of the inhibitor. Revaccination experiments showed that the effects of both inhibitor and interference may be overcome by repeated administration of the vaccine.

Breast Feeding↗

Some experiences with human diploid cell strain-(HDCS) rabies vaccine in pre- and post-exposure vaccinated humans.

HDCS vaccine has been in official use in the F.R.G. for pre- and post-exposure vaccination of man, after having shown its superiority to the Hempt and duck embryo vaccine--as far as compatibility, antigenicity and protective capacity is concerned--since February 1977. HDCS vaccines of both manufacturers, Mérieux/Lyon and Behring/Marburg, did not produce any severe side effects in about 5000 vaccinees in West Germany when conditions of vaccine production were properly observed. The lack of neuropathogenicity of vaccines is stressed. Contamination by bacterial lipopolysaccharides, however, resulted in endotoxin shock in 32 out of 35 vaccinees with one vaccine lot. Testing for pyrogenicity of every vaccine lot should be carefully observed in future. When comparing antigenicity of different vaccine lots of both manufacturers, individual titers of complement-fixing and neutralizing antibodies were correlated with the antigenic values of the vaccines. Duration of immunity after one course of vaccination is approximately 2 years and can be extended by only 1 booster injection for an additional 3 years. Protective capacity of HDCS vaccine (using Essen scheme, 6 applications) seems to be very pronounced. So far, between 1973-1977, 68 individuals under severe risk were vaccinated post-exposure in West Germany and 45 individuals in Iran from 1975-76. No cases of rabies occurred in the vaccinees. HDCS vaccine in man induces a very early antibody response with appearance of IgM rabies specific antibodies on day 3, and IgG rabies specific antibodies on day 7 and an early IgM/IgG antibody conversion at that time.

Antibody Formation↗

Vaccination studies of aspergillosis in turkeys: subcutaneous inoculation with several vaccine preparations followed by aerosol challenge exposure.

Five vaccines were prepared from an isolate of Aspergillus fumigatus: a culture filtrate vaccine (I), a spore vaccine (II), a mycelial vaccine (III), and 2 germling vaccines (IV and V). The 2 germling vaccines were produced on different media. Two experiments were conducted to test the vaccines for efficacy in groups of 21 turkey poults by giving each bird 2 subcutaneous inoculations of the respective vaccine at 1 and 2 weeks of age. The birds were challenge exposed to an aerosol of spores of A fumigatus at 1 month of age. The 2 experiments differed only in the challenge exposure. In experiment 1, 38% of the poults were protected when vaccinated with an A fumigatus germling vaccine (IV) and challenge exposed with a dose of aerosolized A fumigatus spores that killed 100% of the nonvaccinated controls. Onset of postchallenge-exposure deaths were delayed by 2 days in the turkeys given vaccine IV. In experiment 2, 48% of the poults were protected when given germling vaccine IV, whereas 62% to 86% of the poults in the nonvaccinated and 3 other vaccine groups died. In experiment 2, 50% of the poults given a mycelial vaccine (III) were protected. Torticollis was a frequent sign of the disease in experiment 2.

Aerosols↗

Allergic disease at the age of 7 years after pertussis vaccination in infancy: results from the follow-up of a randomized controlled trial of 3 vaccines.

OBJECTIVE: To prospectively assess sensitization rates and the development of allergic diseases in a follow-up of a randomized controlled pertussis vaccine trial. SETTING: Two-month-old infants were the subject of this double-blind study in 1992 in a collaboration between the Pediatric Clinic and the Primary Care Centers in Linköping. PATIENTS AND INTERVENTION: Allergic diseases were evaluated in 667 children, who were randomized to 1 of 4 vaccine groups: a 2-component, a 5-component, or a whole cell pertussis vaccine (all of which were administered with the diphtheria and tetanus toxoids vaccine) and the diphtheria and tetanus toxoids vaccine alone. Allergy development was assessed by questionnaires (n = 667) and skin prick tests (n = 538) at the age of 7 years. MAIN OUTCOME MEASURES: Allergic diseases and skin prick test results at the age of 7 years. RESULTS: The cumulative incidence of allergic diseases was 34.9%, and was similar in the 4 groups (33.3%-37.3%, P =.89), even after adjusting for family history, sex, pets, dampness, environmental smoking at home, and other living conditions. Positive skin prick test results were more prevalent, however, after vaccination with the 2-component acellular vaccine (19.4%) than in the other 3 groups (11.1%-13.5%, adjusted for confounding factors, P =.01). Furthermore, allergic rhinoconjunctivitis was more common in children who were initially immunized with the 2-component pertussis vaccine and received a booster dose with an acellular vaccine compared with those who received no booster vaccination (relative risk, 3.6; 95% confidence interval, 1.1-12.0). CONCLUSION: Pertussis vaccination in infancy with any of these vaccines was not associated with allergic manifestations at the age of 7 years, apart from a higher prevalence of positive skin prick test results after an experimental 2-component vaccine, which is no longer in use.

Asthma↗

Are parental vaccine safety concerns associated with receipt of measles-mumps-rubella, diphtheria and tetanus toxoids with acellular pertussis, or hepatitis B vaccines by children?

OBJECTIVES: To identify parental perceptions regarding vaccine safety and assess their relationship with the immunization status of children. DESIGN, SETTING, AND PARTICIPANTS: Case-control study based on a survey of a sample of households participating in the 2000-2001 National Immunization Survey, a quarterly random-digit-dialing sample of US children aged 19 to 35 months. Three groups of case children not up-to-date for 3 vaccines were compared with control children who were up-to-date for each respective vaccine. Main Outcome Measure Measles-containing or measles-mumps-rubella, diphtheria and tetanus toxoids and pertussis or diphtheria and tetanus toxoids with acellular pertussis, and hepatitis B vaccination coverage. RESULTS: Among those sampled from the 2000-2001 National Immunization Survey, the household response rate was 2315 (52.1%) of 4440. Most respondents (>90%) in all groups believed vaccinations are important. In each case-control group, there was no significant difference between the percentage of case and control parents expressing general vaccine safety (range, 53.5%-64.1%). However, case parents were more likely to have asked that their child not be vaccinated for reasons other than illness (range, 10.2%-13.7% vs range, 2.9%-5.3%, respectively) and to believe their children received too many vaccinations (range, 3.4%-7.6% vs range, 0.8%-1.0%, respectively). Among the case-control group receiving a measles-containing or measles-mumps-rubella vaccination, only a small percentage of parents knew about the alleged association between autism and measles-mumps-rubella vaccinations (8.2%), and case parents were more likely to believe it than control parents (4.4% vs 1.5%, respectively; chi(2) P =.04). CONCLUSIONS: Despite belief in the importance of immunization by a vast majority of parents, the majority of parents had concerns regarding vaccine safety. Strategies to address important misperceptions about vaccine safety as well as additional research assessing vaccine safety are needed to ensure public confidence.

Adult↗

Immune response of mice to immunization with subunit influenza A vaccine in DTP vaccine.

Experiments were carried out to examine the initial feasibility of immunizing infants and children with inactivated influenza virus vaccine combined with diphtheria-tetanus-pertussis (DTP) vaccine. Groups of mice were immunized with saline vaccine or vaccine mixed with DTP: three doses of vaccine were given 3 weeks apart, and the antibody response and resistance to challenge infection were tested 3 weeks after the 1st and 3rd immunizations. The results showed that the antibody response and immunity to challenge virus infection were significantly greater for mice given vaccine in DTP than for mice given saline vaccine alone. Comparison of the response to graded doses of vaccine in saline or DTP indicated that vaccine in DTP was > 250-fold more effective in inducing serum antibody and protection than saline vaccine alone. The enhancing activity of DTP was significant for the alum component alone; however, most of the adjuvant effect was from the antigen components of the DTP vaccine. The results suggest that immunization against influenza in infants and young children could be achieved by combining small amounts of influenza antigen with DTP vaccines; however, the present results have been obtained in mice, and, since the responses to vaccines and adjuvants vary from species to species, the present results cannot be used to indicate similar results in human volunteers. The results indicate the potential value of an immunization procedure which should be tested in volunteers and which could provide a simple strategy for the immunization of at-risk infants and children against influenza.

Adjuvants, Immunologic↗

Vaccination of puppies born to immune dams with a canine adenovirus-based vaccine protects against a canine distemper virus challenge.

None of the currently available distemper vaccines provides a satisfactory solution for the immunization of very young carnivores in the face of maternal-derived immunity. Since mucosal immunization with replication-competent adenovirus-based vaccines has been proven effective in the face of passive immunity against the vector, it has the potential to provide a solution for the vaccination of young puppies born to canine distemper virus (CDV)-immune dams. We report the engineering and the characterization of two replication-competent canine adenovirus type 2 (CAV2)-based vaccines expressing, respectively, the CDV hemagglutinin (HA) and fusion (F) antigens. We first demonstrated that the intranasal vaccination with a mixture of both recombinant CAV2s provides an excellent level of protection in seronegative puppies, confirming the value of replication-competent adenovirus-based vectors for mucosal vaccination. In contrast, intranasal immunization with the same vaccine of puppies born to CDV- and CAV2-immune dams, failed to activate specific and protective immune responses. We hypothesized that an active CAV2 infection occurred while puppies were in close contact with the vaccinated dams in the breeding units and that the resulting active mucosal immunity interfered with the intranasal administration of CAV2-based CDV vaccine. However, when puppies born to CDV- and CAV2-immune dams were vaccinated subcutaneously with the CAV2-based CDV vaccine, significant seroconversion and solid protective immunity were triggered despite pre-existing systemic immunity to the vector. This latter result is surprising and suggests that subcutaneous vaccination with a replication-competent recombinant CAV2 may be an efficient strategy to overcome both passive and active adenovirus specific immunity in the dog. From a practical point of view, this could pave the way for an original strategy to vaccinate young puppies in the face of maternal-derived immunity.

Adenoviruses, Canine↗

An evaluation of the effects of thimerosal on neurodevelopmental disorders reported following DTP and Hib vaccines in comparison to DTPH vaccine in the United States.

Thimerosal is an ethylmercury (49.55% mercury by weight) preservative historically added to some vaccines. Toxicokinetic studies showed children in the United States received doses of mercury from Thimerosal-containing vaccines (TCVs) in excess of safety guidelines. In the United States during the 1990s, diphtheria-tetanus-pertussis (DTP) and Haemophilus influenzae type b (Hib) vaccines (maximally, 50 mug mercury per joint administration) and diphtheria-tetanus-pertussis-Haemophilus influenzae type b (DTPH) vaccines (25 mug mercury per administration) were given to children in the same childhood vaccination schedule at 2, 4, 6, and 15-18 mo, so that children receiving DTP and Hib vaccines may have maximally received an additional 100 mug more mercury exposure from TCVs than children administered DTPH vaccines. A case-control epidemiological study of neurodevelopmental disorders (NDs) reported to the Vaccine Adverse Event Reporting System (VAERS) (online public access version; updated 31 August 2004) following administration of DTP vaccines in comparison DTPH vaccines manufactured by Lederle Laboratories (Pearl River, NY) from 1994 through 1998 was undertaken. Significantly increased odds ratios for autism, speech disorders, mental retardation, infantile spasms, and thinking abnormalities reported to VAERS were found following DTP vaccines in comparison to DTPH vaccines with minimal bias or systematic error. Additional ND research should be undertaken in the context of evaluating mercury-associated exposures, especially since in 2005 the Institute of Medicine issued a report calling into question handling of vaccine safety data by the National Immunization Program of the Centers for Disease Control and Prevention.

Bacterial Capsules↗