Seroprotection against serogroup C meningococcal disease in adolescents in the United Kingdom: observational study

Objective To determine the persistence of bactericidal antibody titres following immunisation with serogroup C meningococcal glycoconjugate vaccine at age 6-15 years in order to examine changes in persistence of antibodies with age.Design Observational study.Setting Secondary and tertiary educational institutions in the United Kingdom.Participants Healthy adolescents aged 11-20 years previously immunised between 6 and 15 years of age with one of the three serogroup C meningococcal vaccines.Intervention Serum obtained by venepuncture.Main outcome measures Percentage of participants with (rabbit complement) serum bactericidal antibody titres of at least 1:8; geometric mean titres of serogroup C meningococcal serum bactericidal antibody.Results Five years after immunisation, 84.1% (95% confidence interval 81.6% to 86.3%) of 987 participants had a bactericidal antibody titre of at least 1:8. Geometric mean titres of bactericidal antibody were significantly lower in 11-13 year olds (147, 95% confidence interval 115 to 188) than in 14-16 year olds (300, 237 to 380) and 17-20 year olds (360, 252 to 515) (P<0.0001 for both comparisons). Within these age bands, no significant difference in geometric mean titres of bactericidal antibody between recipients of the different serogroup C meningococcal vaccines was seen. More than 70% of participants had received a vaccine from one manufacturer; in this cohort, geometric mean titres were higher in those immunised at aged 10 years or above than in those immunised before the age of 10.Conclusions Higher concentrations of bactericidal antibody are seen five years after immunisation with serogroup C meningococcal vaccine at age 10 years or above than in younger age groups, possibly owing to immunological maturation. This provides support for adolescent immunisation programmes to generate sustained protection against serogroup C meningococcal disease not only for the vaccine recipients but also, through the maintenance of herd immunity, for younger children.     

Comparison of one- and two-dose regimens of influenza vaccine for elderly men.

In November and December 1984, 102 male residents of a long-term care facility (mean age 74.6 [extremes 59 and 97] years) received 0.5 ml of trivalent inactivated whole-virion influenza vaccine, containing 15 micrograms of the hemagglutinin of each of A/Philippines/2/82 (H3N2), A/Chile/83 (H1N1) and B/USSR/83. A second dose of the vaccine was administered to a subgroup of 55 randomly chosen subjects 8 weeks later. Serum samples were collected from all the subjects before and 4, 8, 12 and 16 weeks after administration of the first dose and were assayed for hemagglutinin-inhibiting (HAI) antibody to each of the three antigens. At 8 weeks there were significant increases (p less than 0.05) in the geometric mean titre of antibody and in the proportion of subjects with HAI antibody titres of 1:40 or more (except to the B/USSR antigen) in both groups. There were no differences between the groups at 8 weeks or at 16 weeks (8 weeks after administration of the second dose of vaccine) in the frequency of seroconversion, the geometric mean titre or the proportion of subjects with HAI antibody titres of 1:40 or more. Overall, 60%, 32% and 13% of the 102 subjects had titres of 1:40 or more to the A/Philippines, A/Chile and B/USSR antigens respectively at 16 weeks. The results suggest that a second dose of influenza vaccine given 8 weeks after the first does not enhance the immune response in elderly men and that a substantial proportion of this population remains unprotected against infection (having HAI antibody titres of less than 1:40) during the influenza season.     

Persistence of antibody after accelerated immunisation with diphtheria/tetanus/pertussis vaccine.

OBJECTIVE--To determine the persistence of antibody to diphtheria, tetanus, and pertussis in children receiving an accelerated schedule of primary immunisation. DESIGN--Controlled study of antibody testing of blood samples from children immunised according to various schedules: three doses of triple vaccine completed at 8-13 calendar months, 6-7 calendar months, before 6 calendar months, or three doses followed by diphtheria/tetanus before age 2. SETTING--Plymouth Health Authority. SUBJECTS--129 children aged 4 years who had received three doses of diphtheria/tetanus/pertussis vaccine with or without a diphtheria/tetanus booster. MAIN OUTCOME MEASURES--Diphtheria and tetanus antitoxin concentrations and antibody titres to pertussis toxin, filamentous haemagglutinin, and agglutinogens 2 and 3. RESULTS--All children had protective concentrations of antitoxin to diphtheria and tetanus (greater than or equal to 0.01 IU/ml). There was no evidence of a significant difference in diphtheria or tetanus antitoxin concentrations and pertussis antibody titres in children immunised with an accelerated course (third dose of triple vaccine before 6 months) compared with those who received a longer course (third dose at 8-13 months) with no booster (geometric mean antitoxin concentration 0.411 (95% confidence interval 0.273 to 0.618) v 0.426 (0.294 to 0.616) for diphtheria and 0.358 (0.231 to 0.556) v 0.299 (0.197 to 0.453) for tetanus; geometric mean antibody titres 903 (500 to 1631) v 1386 (848 to 2266) for pertussis filamentous haemagglutinin, 179 (130 to 248) v 232 (167 to 322) for pertussis toxin, and 2002 (1276 to 3142) v 3591 (2220 to 5809) for agglutinogens 2 and 3). CONCLUSION--Immunisation with three doses of triple vaccine at monthly intervals completed before 6 months of age probably provides adequate protection against diphtheria, tetanus, and whooping cough which will persist until the age of the preschool booster.     

Presence of maternal anti-HBs antibodies does not influence hepatitis B vaccine response in Brazilian neonates

Recently, it was suggested that maternal hepatitis B surface antigen antibodies (anti-HBs) acquired transplacentally could play a negative role in newborn infants' immune response to the hepatitis B vaccine. We compared the hepatitis B virus (HBV) vaccine response in infants born to mothers previously vaccinated against HBV (n = 91) to infants born to mothers who were not previously vaccinated (n = 221). All newborn infants received three intramuscular doses (10 μg) of HBV vaccine (Butang?) at 0,1 and six months. The first dose was administered at the maternity hospital within 12 h of birth. The geometric mean titres of anti-HBs were not different among newborn infants born to mothers who were anti-HBs-negative (492.7 mIU/mL) and anti-HBs-positive (578.7 mIU/mL) (p = 0.38). Eight infants did not respond to the HBV vaccine. Of them, six were born to anti-HBs-negative mothers and two were born to mothers with anti-HBs titres less than 50 mlU/mL. Despite the mother's anti-HBs-positive status, our data show a good immunogenicity of the Brazilian HBV recombinant vaccine in neonates.     

Influenza subunit vaccine: antibody responses to one and two doses of vaccine and length of response,with particular reference to the elderly.

Antibody responses to subunit influenza vaccine prepared against A2/England/42/72 (h3n2) were studied in 69 volunteers aged 60 and over and 231 aged 59 and below over 12 months in 1973 and 1974. After two doses of vaccine seroconversion frequencies and geometric mean haemagglutination-inhibition (HI) titres were higher in the elderly, but no differences were observed between the two groups in the length of their responses. Sixteen (23%) of the elderly volunteers seroconverted only after receiving a second dose of vaccine or seroconverted twice after receiving both doses of vaccine. It was considered justifiable, therefore, to recommend the continuation of a two-dose schedule for patients in a high-risk category. Within 30 weeks of vaccination 87 (29%) volunteers had considerably reduced HI titres (less than 48), which might indicate potential susceptibility to influenza during an epidemic, and the number had risen to 132 (44%) by 50 weeks. It was suggested that high-risk patients should receive annnual vaccination two to four months before the possible epidemic period.     

Failure to deliver hepatitis B vaccine: confessions from a genitourinary medicine clinic.

OBJECTIVE--To audit hepatitis B immunisation of homosexual or bisexual men in a genitourinary medicine clinic. DESIGN--Retrospective case note review of all homosexual and bisexual men presenting to a genitourinary clinic as new patients during 12 months in 1988 and follow up review of notes to May 1990. SETTING--One department of genitourinary medicine, Middlesex Hospital. PATIENTS--758 homosexual or bisexual men, of whom 207 started a course of hepatitis B vaccine in 1988. Case notes were unavailable for one patient. MAIN OUTCOME MEASURES--The proportion of patients screened for hepatitis B virus markers, the proportion of susceptible patients immunised, the proportion completing the vaccine course, and the proportion rendered immune. RESULTS--25 men had been previously tested for hepatitis markers; of the 732 not previously tested, 440 (60.1%) were screened for hepatitis B markers. 207 (69%) of the 300 patients without hepatitis B serological markers started the vaccine course, and 141 (68%) completed it, with 75 (84%) of the 89 tested after immunisation being immune. An estimated 24% of susceptible new patients were rendered immune as a result of the immunisation policy. Patients who presented with a further episode of a sexually transmitted disease were more likely to have been screened (25% v 12%, p less than 0.0001) and immunised (31% v 18% p = 0.02); those known or found to be positive for HIV antibody were more likely to have been screened (23% v 14%, p = 0.047) but less likely to have been immunised (6% v 17%, p = 0.004). CONCLUSIONS--The major failure was that in not screening; failure to immunise patients found to be susceptible and failure of compliance with the vaccine course contributed. Non-response to the vaccine was of minor importance. Improvements in vaccine delivery are required. IMPLICATIONS--Other providers should be encouraged to review their performance.     

Immune response to a new hepatitis B vaccine in healthcare workers who had not responded to standard vaccine: randomised double blind dose-response study.

OBJECTIVE: To evaluate the immunogenicity and reactogenicity of a new triple S recombinant hepatitis B vaccine in a cohort of healthy people in whom currently licensed hepatitis B vaccines had persistently not induced an immune response. DESIGN: Single centre, randomised, double blind, dose-response study. SETTING: Research vaccine evaluation centre at a teaching hospital. SUBJECTS: 100 healthcare workers aged 18-70 years with a history of failure to seroconvert after at least four doses of a licensed hepatitis B vaccine containing the S component. INTERVENTION: Each subject was randomly allocated two doses of 5, 10, 20, or 40 micrograms of a new hepatitis B vaccine two months apart. MAIN OUTCOME MEASURES: Immunogenicity of the four doses. Seroconversion and seroprotection were defined as an antibody tire > 10 IU/l and > 100 IU/l respectively against an international antibody standard. RESULTS: 69 subjects seroconverted after a single dose of the vaccine. After the booster vaccination one other subject seroconverted, bringing the overall seroconversion rate to 70%. Fifteen subjects given 5 micrograms of vaccine, 19 given 10 micrograms, 16 given 20 micrograms, and 20 given 40 micrograms seroconverted. Seroconversion rates in the four antigen dose groups were 60% (15/25), 76% (19/25), 64% (16/25), and 80% (20/25). After the booster dose there was no significant dose-response effect on the overall seroconversion rate, although the small sample size meant that a clinically important dose-response could not be ruled out. CONCLUSION: A single dose of 20 micrograms of the vaccine was as effective as two doses of either 40 micrograms or 20 micrograms of this vaccine formulation in terms of seroconversion, seroprotection, and geometric mean titres.     

The humoral immune response and the productivity of laying hens kept on the ground or in cages

The effects of two different keeping systems on the humoral immune response and productivity were compared for 80 laying hens, divided into four groups. Two groups each of 20 hens were kept on the ground and two were kept in cages. All the birds were immunised subcutaneously with human serum immunoglobulin G (IgG) at a dose of 100(microg per injection. The immunisations were performed twice at 4-week intervals. The lipopeptide Pam(3)Cys-Ser-(Lys)(4) was used as an adjuvant at a dose of 0.25mg per injection in one group from each housing system. In the second group from each housing system, the hens were immunised without any adjuvant (antigen control groups). The mean egg yield was significantly higher in both the antigen control group and the adjuvant group, when laying hens were kept in cages. Total egg weight remained constant in both of the housing systems. Keeping hens in cages resulted in higher mean specific antibody titres and mean immunoglobulin Y concentrations in the egg yolk.     

Immunogenicity of a killed whole Neospora caninum tachyzoite preparation formulated with different adjuvants

A killed whole Neospora caninum tachyzoite preparation was formulated with various adjuvants and tested for its immunogenicity in cattle. The adjuvants used were: Havlogen, a polymer of acrylic acid cross-linked with polyallylsucrose; Polygen, a non-particulate copolymer; a mixture of Havlogen and Bay R-1005, which is a preparation of free base synthetic glycolipids; and Montanide ISA 773, a water-in-oil emulsion made with a mixture of metabolisable and mineral oils. Immune responses in immunised cattle were compared with those of cattle experimentally infected with culture-derived N. caninum tachyzoites. The overall mean serum IFAT titres were significantly higher (P < 0.05) in experimentally infected cattle compared with all immunised cattle. Nonetheless, the maximum antibody titres of the immunised cattle, which were obtained following the third immunisation, were within the range of titres previously described for naturally infected cattle. The overall mean serum IFAT titres were significantly higher (P < 0.05) in cattle immunised with the killed tachyzoite preparation formulated with Polygen and with the mixture of Havlogen and Bay R-1005, compared with cattle immunised with the Havlogen- and Montanide-based preparations. Two of the four adjuvant preparations were able to induce cell-mediated immune responses similar to those of the experimentally infected cattle. The Havlogen-adjuvanted tachyzoite preparation elicited N. caninum-specific proliferation of peripheral blood mononuclear cells statistically similar (P = 0.095) to that of the infected animals. Peripheral blood mononuclear cells from animals immunised with the Polygen-adjuvanted tachyzoite preparation produced interferon-gamma concentrations of similar magnitude (P = 0.17) to those from the infected animals. Polygen was one of two adjuvants that elicited the highest antibody responses, and was the only adjuvant that induced interferon-gamma levels similar to those of the infected heifers.     

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.     

Adenovirus-5-vectored P. falciparum vaccine expressing CSP and AMA1. Part B: safety, immunogenicity and protective efficacy of the CSP component

Background

A protective malaria vaccine will likely need to elicit both cell-mediated and antibody responses. As adenovirus vaccine vectors induce both these responses in humans, a Phase 1/2a clinical trial was conducted to evaluate the efficacy of an adenovirus serotype 5-vectored malaria vaccine against sporozoite challenge.

Methodology/Principal Findings

NMRC-MV-Ad-PfC is an adenovirus vector encoding the Plasmodium falciparum 3D7 circumsporozoite protein (CSP). It is one component of a two-component vaccine NMRC-M3V-Ad-PfCA consisting of one adenovector encoding CSP and one encoding apical membrane antigen-1 (AMA1) that was evaluated for safety and immunogenicity in an earlier study (see companion paper, Sedegah et al). Fourteen Ad5 seropositive or negative adults received two doses of NMRC-MV-Ad-PfC sixteen weeks apart, at particle units per dose. The vaccine was safe and well tolerated. All volunteers developed positive ELISpot responses by 28 days after the first immunization (geometric mean 272 spot forming cells/million[sfc/m]) that declined during the following 16 weeks and increased after the second dose to levels that in most cases were less than the initial peak (geometric mean 119 sfc/m). CD8+ predominated over CD4+ responses, as in the first clinical trial. Antibody responses were poor and like ELISpot responses increased after the second immunization but did not exceed the initial peak. Pre-existing neutralizing antibodies (NAb) to Ad5 did not affect the immunogenicity of the first dose, but the fold increase in NAb induced by the first dose was significantly associated with poorer antibody responses after the second dose, while ELISpot responses remained unaffected. When challenged by the bite of P. falciparum-infected mosquitoes, two of 11 volunteers showed a delay in the time to patency compared to infectivity controls, but no volunteers were sterilely protected.

Significance

The NMRC-MV-Ad-PfC vaccine expressing CSP was safe and well tolerated given as two doses, but did not provide sterile protection.

Trial Registration

ClinicalTrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00392015","term_id":"NCT00392015"}}NCT00392015     

Phase I trial of an alhydrogel adjuvanted hepatitis B core virus-like particle containing epitopes of Plasmodium falciparum circumsporozoite protein

The objectives of this non-randomized, non-blinded, dose-escalating Phase I clinical trial were to assess the safety, reactogenicity and immunogenicity of ICC-1132 formulated with Alhydrogel (aluminum hydroxide) in 51 healthy, malaria-naive adults aged 18 to 45 years. ICC-1132 (Malariavax) is a recombinant, virus-like particle malaria vaccine comprised of hepatitis core antigen engineered to express the central repeat regions from Plasmodium falciparum circumsporozoite protein containing an immunodominant B [(NANP)(3)] epitope, an HLA-restricted CD4 (NANPNVDPNANP) epitope and a universal T cell epitope (T*) (amino acids 326-345, NF54 isolate). We assessed an Alhydrogel (aluminum hydroxide)-adjuvanted vaccine formulation at three ICC-1132 dose levels, each injected intramuscularly (1.0 mL) on study days 0, 56 and 168. A saline vaccine formulation was found to be unstable after prolonged storage and this formulation was subsequently removed from the study. Thirty-two volunteers were followed for one year. Local and systemic adverse clinical events were measured and immune responses to P. falciparum and hepatitis B virus core antigens were determined utilizing the following assays: IgG and IgM ELISA, indirect immunofluorescence against P. falciparum sporozoites, circumsporozoite precipitin (CSP) and transgenic sporozoite neutralization assays. Cellular responses were measured by proliferation and IL-2 assays. Local and systemic reactions were similarly mild and well tolerated between dose cohorts. Depending on the ICC-1132 vaccine concentration, 95 to 100% of volunteers developed antibody responses to the ICC-1132 immunogen and HBc after two injections; however, only 29-75% and 29-63% of volunteers, respectively, developed malaria-specific responses measured by the malaria repeat synthetic peptide ELISA and IFA; 2 of 8 volunteers had positive reactions in the CSP assay. Maximal transgenic sporozoite neutralization assay inhibition was 54%. Forty-seven to seventy-five percent demonstrated T cell proliferation in response to ICC-1132 or to recombinant circumsporozoite protein (rCS) NF-54 isolate. This candidate malaria vaccine was well tolerated, but the vaccine formulation was poorly immunogenic. The vaccine may benefit from a more powerful adjuvant to improve immunogenicity. TRIAL REGISTRATION: ClinicalTrials.gov NCT00587249.     

Priming of human papillomavirus type 11-specific humoral and cellular immune responses in college-aged women with a virus-like particle vaccine

In this study, we evaluated the potency of a human papillomavirus (HPV) virus-like particle (VLP)-based vaccine at generating HPV type 11 (HPV-11)-specific cellular and humoral immune responses in seronegative women. The vaccine was administered by intramuscular immunizations at months 0, 2, and 6. A fourth immunization was administered to approximately half of the women at month 12. All vaccine recipients had positive HPV-11 VLP-specific lymphoproliferative responses at month 3 following the second immunization (geometric mean lymphoproliferative stimulation index [SI] = 28.4; 95% confidence interval [CI] = 16.9 to 48.0) and HPV-11 VLP-specific antibody titers following the first immunization at month 1 (geometric mean antibody titer = 53.9 milli-Merck units/ml, 95% CI, 34.8 to 83.7). In contrast, lymphoproliferative and antibody titer responses were never detected in the participants who received placebo. Relatively homogeneous lymphoproliferative responses were observed in all vaccinated women. The mean lymphoproliferative SI of the vaccinated group over the first 12 months of the study was 7.6-fold greater than that of the placebo group following the initial immunization. The cellular immune responses generated by VLP immunization were both Th1 and Th2, since peripheral blood mononuclear cells from vaccinees, but not placebo recipients, secreted interleukin 2 (IL-2), IL-5, and gamma interferon (IFN-gamma) in response to in vitro stimulation with HPV-11 VLP. The proliferation-based SI was moderately correlated with IFN-gamma production and significantly correlated with IL-2 production after the third immunization (P = 0.078 and 0.002, respectively). The robust lymphoproliferative responses were specific for HPV-11, since SIs generated against bovine papillomavirus and HPV-16 VLPs were not generally observed and when detected were similar pre- and postimmunization.     

Maternal transfer of humoral specific and non-specific immune parameters to sea bream (Sparus aurata) larvae

Immunisation of sea bream (Sparus aurata L.) broodstock with a novel vaccine mixture of Photobacterium damsela subsp. piscicida SK7 (Phdp) was performed during the period of egg development and the changes in specific and non-specific humoral immune parameters were measured. Total immunoglobulin level, specific antibody titre, anti-protease activity and lysozyme activity were significantly higher in immunised parents compared to the control. After spawning significantly higher anti-protease activity, lysozyme activity and total immunoglobulin level were detected in the eggs from immunised parents. Specific antibody titres against Phdp were only detected in the eggs from the immunised parents. The larvae from immunised parents also expressed significantly higher levels of specific and non-specific humoral immune parameters compared to the controls. A small amount of total immunoglobulin was detected in larvae decreasing gradually until day 8 post-hatching and then an increase was measured in larvae from immunised parents, whereas no immunoglobulin was detected at days 4, 6 and 8 in larvae from non-immunised parents. The specific antibody titre against Phdp was detected only in larvae from immunised broodstock until day 14 post-hatching. The higher humoral immune parameters in eggs and larvae from immunised parents in comparison to eggs and larvae from non-immunised parents, suggest transfer of maternal specific and non-specific immune factors.     

Systemic immunization with pneumococcal polysaccharide vaccine induces a predominant IgA2 response of peripheral blood lymphocytes and increases of both serum and secretory anti-pneumococcal antibodies

Ig class-, and IgA and IgG subclass-specific immune responses to a 23 valent pneumococcal polysaccharide vaccine were studied at a single-cell level in the peripheral blood of systemically immunized adults. With a solid phase enzyme-linked immunospot (ELISPOT) assay, PBMC from immunized individuals were assayed for spontaneous Ag-specific antibody (Ab) production before, and on days 7, 14, and 28 after vaccination. On the day of immunization, no spontaneous Ag-specific Ab-secreting cells could be detected. On day 7 after vaccination, a high frequency of cells secreting Ab specific for pneumococcal polysaccharides (PPS) was observed. The IgA class comprised 79% (geometric mean) of the Ag-specific Ab-secreting cells, whereas IgG- and IgM-secreting cells accounted for 12% and 9%, respectively. The majority of Ag-specific IgA-secreting cells produced Ab of the IgA2 isotype. Serum, saliva, and tears collected before and on days 7, 14, and 28 after vaccination were assayed for specific Ab to the vaccine (anti-PPS Ab) by an ELISA. Serum IgA anti-PPS Ab showed the highest increase after vaccination with a 19-fold increase (geometric mean) which peaked on day 14. However, the ratio of Ag-specific polymeric vs monomeric IgA did not change after immunization. Serum IgG and IgM anti-PPS Ab displayed mean increases of 5.5-fold and 5.6-fold, respectively, on day 14. The most pronounced increase of salivary anti-PPS Ab was observed in the IgG class (4.5-fold on day 28) followed by IgM (4-fold on day 28), IgA (2.0-fold on day 14), IgA1 (2.4-fold on day 14) and IgA2 (2.0-fold on day 14). The levels of total IgA, IgG, and IgM in saliva did not change significantly throughout the course of immunization. IgG and IgM anti-PPS Ab levels in tears increased less than in saliva, whereas IgA behaved similarly as in saliva. There were no significant differences in the Ag-specific increase rates between the IgA, IgG, and IgM isotypes in tears.     

Active immunisation of mice with GnRH lipopeptide vaccine candidates: Importance of T helper or multi-dimer GnRH epitope

Active immunisation against gonadotropin releasing hormone (GnRH) is a potential alternative to surgical castration. This study focused on the development of a GnRH subunit lipopeptide vaccine. A library of vaccine candidates that contained one or more (up to eight) copies of monomeric or dimeric GnRH peptide antigen, an adjuvanting lipidic moiety based on lipoamino acids, and an additional T helper epitope, was synthesised by solid phase peptide synthesis. The candidates were evaluated in vivo in order to determine the minimal components of this vaccine necessary to induce a systemic immune response. BALB/c mice were immunised with GnRH lipopeptide conjugates, co-administered with or without Complete Freund’s Adjuvant, followed by two additional immunisations. Significant GnRH-specific IgG titres were detected in sera obtained from mice immunised with four of the seven lipopeptides tested, with an increase in titres observed after successive immunisations. This study highlights the importance of for epitope optimisation and delivery system design when producing anti-hapten antibodies in vivo. The results of this study also contribute to the development of future clinical and veterinary immunocontraceptives.     

Green propolis phenolic compounds act as vaccine adjuvants, improving humoral and cellular responses in mice inoculated with inactivated vaccines

Adjuvants play an important role in vaccine formulations by increasing their immunogenicity. In this study, the phenolic compound-rich J fraction (JFR) of a Brazilian green propolis methanolic extract stimulated cellular and humoral immune responses when co-administered with an inactivated vaccine against swine herpesvirus type 1 (SuHV-1). When compared to control vaccines that used aluminium hydroxide as an adjuvant, the use of 10 mg/dose of JFR significantly increased (p < 0.05) neutralizing antibody titres against SuHV-1, as well as the percentage of protected animals following SuHV-1 challenge (p < 0.01). Furthermore, addition of phenolic compounds potentiated the performance of the control vaccine, leading to increased cellular and humoral immune responses and enhanced protection of animals after SuHV-1 challenge (p < 0.05). Prenylated compounds such as Artepillin C that are found in large quantities in JFR are likely to be the substances that are responsible for the adjuvant activity.     

乙型肝炎血源疫苗皮内接种4年效果观察

为了解乙型肝炎血源疫苗皮内接种的持久效果,选ＨＢｓＡｇ、抗－ＨＢｓ和抗－ＨＢｃ均（－）的９～１１岁儿童１０３名,随机分成４组,分别皮内接种１μｇ×４和３μｇ×４（均按０,１,２,５月程序）和肌肉接种１０μｇ×３和３０μｇ×３（各按０,１,２月程序）。首针后４８月时,１μｇ、３μｇ、１０μｇ和３０μｇ组抗－ＨＢｓ≥１０ｍＩＵ／ｍＩ者各为６９．２％,８０．０％、９２．３％和８１．８％;ＧＭＴ则为１４．５,７９．０,４４．８和７０．９ｍＩＵ／ｍｌ,３μｇ×４皮内免疫的近期和远期效果与肌肉组３０μｇ×３相似,宜于某些人群采用     

Immunogenicity and safety assessment of the Cuban recombinant hepatitis B vaccine in healthy adults.

Manufactures of biotechnological/biological products (including vaccines) frequently make changes to manufacturing processes of products both during development and after approval. In our case, a non-inferiority bridging study was carried out to demonstrate that changes in the production plant facilities of Cuban recombinant hepatitis B vaccine, Heberbiovac HB, did not affect the safety and immunogenicity of the vaccine. This controlled, randomized, doubled-blinded trial included 501 volunteers, aged between 20 and 64, who were given three doses of vaccine (20 microg HBsAg/mL) at month 0, 1, and 2. Four lots were evaluated (three corresponding to the new production facilities and a control one produced in the older facilities). One month after the third dose, were observed protective levels of anti-HBsAg in 97% of the subjects that concluded the study with a geometric mean antibody titer (GMT) of 931.18 IU/L. Normal values of body mass index (BMI), the younger ages, and being a female, were significantly related to a good antibody response. The vaccine was well tolerated. Pain at the injection site was the most commonly reported symptom. We conclude that Heberbiovac HB vaccine maintains its characteristics after the modifications carried out in the production plant facilities and both, lot obtained in previous facilities and in the new ones, are comparable in terms of safety and immunogenicity.     

Toxoplasma gondii Protein Disulfide Isomerase (TgPDI) Is a Novel Vaccine Candidate against Toxoplasmosis

Toxoplasma gondii is a ubiquitous protozoan parasite that can infect all warm-blooded animals, including both mammals and birds. Protein disulfide isomerase (PDI) localises to the surface of T. gondii tachyzoites and modulates the interactions between parasite and host cells. In this study, the protective efficacy of recombinant T. gondii PDI (rTgPDI) as a vaccine candidate against T. gondii infection in BALB/c mice was evaluated. rTgPDI was expressed and purified from Escherichia coli. Five groups of animals (10 animals/group) were immunised with 10, 20, 30, 40 μg of rTgPDI per mouse or with PBS as a control group. All immunisations were performed via the nasal route at 1, 14 and 21 days. Two weeks after the last immunisation, the immune responses were evaluated by lymphoproliferative assays and by cytokine and antibody measurements. The immunised mice were challenged with tachyzoites of the virulent T. gondii RH strain on the 14th day after the last immunisation. Following the challenge, the tachyzoite loads in tissues were assessed, and animal survival time was recorded. Our results showed that the group immunised with 30 μg rTgPDI showed significantly higher levels of specific antibodies against the recombinant protein, a strong lymphoproliferative response and significantly higher levels of IgG2a, IFN-gamma (IFN-γ), IL-2 and IL-4 production compared with other doses and control groups. While no changes in IL-10 levels were detected. After being challenged with T. gondii tachyzoites, the numbers of tachyzoites in brain and liver tissues from the rTgPDI group were significantly reduced compared with those of the control group, and the survival time of the mice in the rTgPDI group was longer than that of mice in the control group. Our results showed that immunisation with rTgPDI elicited a protective immune reaction and suggested that rTgPDI might represent a promising vaccine candidate for combating toxoplasmosis.