Rotavirus vaccines (RV) have decreased the infant morbidity and mortality in countries that included RV in their national schedule. Rotavirus vaccination is recommended by the Spanish Society of Pediatrics; however, Spain, as most countries in Europe, has authorized commercialization but not included RV in its national vaccination program. We assessed the impact of RV on the rotavirus hospitalization rate through an interrupted time series analysis. There was a 46.8% (95% CI: 29.3–60.2) decrease on the rotavirus hospitalizations rate in the study region after RV commercialization in 2006. Currently there is limited evidence about the impact of RV in Europe, especially among countries not offering systematic vaccination in their national schedule. Documentation of RV coverage, effectiveness and impact is urgently needed in these countries.
In areas were human visceral leishmaniasis (VL) is endemic, the domestic dog is the main parasite reservoir in the infectious cycle of Leishmania infantum. Development of prophylactic strategies to lower the parasite burden in dogs would reduce sand fly transmission thus lowering the incidence of zoonotic VL. Here we demonstrate that vaccination of dogs with a recombinant 14 kDa polypeptide of L. infantum nuclear transport factor 2 (Li-ntf2) mixed with adjuvant BpMPLA-SE resulted in the production of specific anti-Li-ntf2 IgG antibodies as well as IFN-γ release by the animals' peripheral blood mononuclear cells stimulated with the antigen. In addition, immunization with this single and small 14 kDa polypeptide resulted in protracted progression of the infection of the animals after challenging with a high dose of virulent L. infantum. Five months after challenge the parasite load was lower in the bone marrow of immunized dogs compared to non-immunized animals. The antibody response to K39, a marker of active VL, at ten months after challenge was strong and significantly higher in the control dogs than in vaccinated animals. At the study termination vaccinated animals showed significantly more liver granulomas and lymphoid hyperplasia than non-vaccinated animals, which are both histological markers of resistance to infection. Together, these results indicate that the 14 kDa polypeptide is an attractive protective molecule that can be easily incorporated in a leishmanial polyprotein vaccine candidate to augment/complement the overall protective efficacy of the final product.
Coccidiosis is a major intestinal disease affecting economically valuable livestock animals such as chickens and turkeys. Economic losses are associated with decreased productivity in afflicted animals. The different Eimeria spp. are the main etiologic agents for that virulent disease. The usefulness of prophylactic and therapeutic anticoccidial compounds has decreased in recent years due to the emergence of drug resistance in Eimeria, together with their possible toxic effect to the human consumers. Despite that, biosecurity and disinfection measures are the cornerstone to control the emergence of the pathogen, the immunization methods proved to be more practical and promising to prevent outbreaks due to coccidia. Since the early 1950s, several attempts were followed to formulate commercial immunotherapies, but up till now none proved to be sufficient. This review summarizes, classifies, and evaluates the trials performed to prevent avian coccidiosis, thereafter introduces an out of frame scientific strategy to find a solution for that emerging parasite.
At the present, no anti-Hepatitis C virus (HCV) HCV vaccine is available, and many patients failed the treatment with new class of HCV inhibitors. In HCV infection, both experimental and clinic evidences indicate that a strong CTL-immune response could have significant therapeutic effects. We developed an innovative anti-HCV CD8+ T immunogen based on the uploading in engineered exosomes of full-length HCV-NS3 protein. HCV NS3 exosomes appeared immunogenic when injected in mice, as proven by the detection of a memory CD8+ T lymphocyte pool two weeks after the last of three immunizations. On the other hand, dendritic cells isolated from PBMCs of HCV infected patients activate autologous HCV NS3-specific CD8+ T lymphocytes upon challenge with HCV NS3 exosomes. These results provide the proof-of-principle that engineered exosomes can boost the CD8+ T cell immunity in HCV-infected patients, thus representing a suitable option for patients resisting the therapies with recently discovered HCV inhibitors.
Mycobacterium ulcerans (MU) infection causes the disfiguring necrotic skin disease, Buruli ulcer (BU). While vaccination with Mycobacterium bovis BCG provides nominal antigenic cross-reactivity for induction of immunity against experimental MU infection, a mycobacterial species with greater genetic homology to Mycobacterium ulcerans may serve as a richer source of cross-protective immunogens and lack the pathological features of MU-based vaccines. Mycobacterium marinum, a highly homologous genetic relative of MU, could be used to satisfy these criteria and, as such, we have generated a recombinant M. marinum strain expressing the immunodominant, protective MU-Ag85A. The immunogenicity and protection achieved by murine vaccination with this strain are superior to standard BCG vaccination and may serve as a foundation for developing more effective BU vaccines.
•Oil-based adjuvants, or their combination with gel, resulted in different immune response in mice.•The protection in the mice immunized with oil and gel was improved in short to long-term.•ISA201+AL showed lower humoral immunity than ISA201, but the protectivity was enhanced.
Until recently, all seasonal influenza vaccines have been trivalent, containing strains A(H1N1), A(H3N2), and one of the two B strain lineages (Yamagata or Victoria), resulting in frequent mismatches between the circulating B strain lineage and that included in the vaccine. A quadrivalent, inactivated, split-virion influenza vaccine (IIV4) containing strains from both B lineages has been developed to address this. We performed an open-label phase III study to assess the immunogenicity and safety of the 2013–2014 Northern Hemisphere formulation of IIV4 in children and adolescents 9–17years of age in Taiwan. Participants were vaccinated with one dose of IIV4 by intramuscular or deep subcutaneous injection. Hemagglutinin inhibition (HAI) titers were measured before and 21days after vaccination. Solicited injection-site and systemic reactions were assessed for up to 7days after vaccination, and adverse events (AEs) were recorded until day 21. One hundred participants were included. Despite relatively high pre-vaccination titers, post-vaccination HAI titers increased for all four strains, with geometric mean ratios (day 21/day 0) of 2.29 for A(H1N1), 2.05 for A(H3N2), 3.33 for B/Massachusetts (Yamagata lineage), and 4.59 for B/Brisbane (Victoria lineage). Post-vaccination seroprotection rates were 99% for A(H3N2) and 100% for A(H1N1), B/Massachusetts, and B/Brisbane. Due to high pre-vaccination titers, rates of seroconversion/significant increase of HAI titer were relatively low at 24% for A(H1N1), 20% for A(H3N2), 39% for B/Massachusetts, and 48% for B/Brisbane. Injection-site pain (56%), myalgia (45%), and malaise (15%) were the most frequently reported solicited reactions, and most solicited reactions were mild or moderate. No treatment-related AEs, immediate unsolicited AEs, unsolicited non-serious injection-site AEs, grade 3 unsolicited AEs, or serious AEs were reported. In conclusion, this study showed that the 2013–2014 Northern Hemisphere formulation of the intramuscular IIV4 was immunogenic and well tolerated by children and adolescents 9–17years of age.
The increasing resistance of many microbial strains to antibiotics, delayed laboratory results, and side effects of many chemotherapeutics has raised the need to search for sensitive diagnostics and new prophylactic strategies especially prevention by vaccination. Understanding the epitope/antibody interaction is the key to constructing potent vaccines and effective diagnostics. B-cell epitope mapping is a promising approach to identifying the main antigenic determinants of microorganisms, in special concern the discontinuous conformational ones. Epitope-based vaccines have remarkable privilege over the conventional ones since they are specific, able to avoid undesirable immune responses, generate long lasting immunity, and are reasonably cheaper. This up-to-date review discusses and compares the different physical, computational, and molecular methods that have been used in epitope mapping. The role of each method in the identification of potent epitopes in viruses, bacteria, fungi, parasites, as well as human diseases are tagged and documented. Simultaneously, frequent combinatorial methods are highlighted. The article aims to assist researchers to design the most suitable protocol for mapping their B-cell epitopes.
The objective of this study is to evaluate the immunization and stress dormant role in humoral and cell mediated response after sub-acute exposure of noise stress and immunomodulatory activity of Indigofera tinctoria (I. tinctoria). Noise stress was done by broadband white noise generator (0–26 kHz), 100 dB, 4 h daily for 15 days and I. tinctoria (300 mg/kg b.w.) administered orally. The animals were divided into eight groups with six animals in each group. All the rats were housed under condition of controlled temperature (26 ± 2 °C) with 12 h light and 12 h dark exposure. In the present study, noise stress significantly increased the corticosterone level in both immunized (76.55 ± 5.17) and un-immunized (66.25 ± 4.87). In sub-acute stress TLC level decreased in un-immunized and increased in immunized. A significant decrease in neutrophil (14.5 ± 3.01) and increase in lymphocyte (86.166 ± 4.83) level was noticed on un-immunized after noise exposure. NAT level was decreased in the un-immunized (40.745 ± 1.95) and increased in immunized (72.625 ± 2.88). The noise stress increased the NBT levels in un-immunized (19.5 ± 1.87) and decreased in immunized (24 ± 2.10). Noise stress shows decreases phagocytic index, avidity index, organ weight and cell count of the spleen, thymus, lymph node in irrespective of whether un-immunized and immunized. Subacute exposure of noise significantly affects humoral (SIC, antibody titter) and cell mediated (LMI, FPT) immunity. Stress further decrease the IL-2, TNF-α, IFN-γ and increase IL-4 cytokine level in serum. This result further concludes that prior immunization of SRBC in animal's act as a vaccination, which helps to prevent noise stress induced impairment in immune system. Orally administered I. tinctoria prevented noise altered immune system. These results also concluded that I. tinctoria supplementation could act as an immunomodulators and suggesting its therapeutic efficacy as an antistressor.
Acinetobacter baumannii has recently crossed all lines once considered harmless, pushing its way as a nosocomial pathogen. It had acquired resistance to almost all available chemotherapies and mainly targets intensive care residents; causing pneumonia and major outbreaks with high mortality rates. This urged the need for preventive methods, which include infection control, non-specific immune-therapy, passive, and active immunization in order to offer vulnerable immune-compromised patients a flare in the dark. Several attempts were done for constructing effective vaccines with promising results. These are precisely classified, documented, and discussed in this up-to-date review.
The safety and efficacy of a new intradermal one dose vaccine containing Porcine Circovirus type 2 (PCV2) antigen – Porcilis® PCV ID – was evaluated in laboratory studies and under field conditions. In addition, the concurrent use with an intradermal Mycoplasma hyopneumoniae vaccine – Porcilis® M Hyo ID ONCE – was evaluated.
Enzootic Pneumonia (EP) caused by Mycoplasma hyopneumoniae results in major economic losses to the swine industry. Hence, the identification of factors that provide protection against EP could help to develop effective vaccines. One such factor that provides partial protection are bacterins. Therefore, the aim of this study was to verify the induction of antibodies against fifteen M. hyopneumoniae antigens, strongly recognized by the swine immune system during natural infection, in mice vaccinated with six commercial bacterins. Each group of mice was inoculated with one bacterin, and seroconversion was assessed by indirect ELISA using recombinant antigens and M. hyopneumoniae 7448 whole cell extract. Sera from one inoculated group recognized antigen MHP_0067, and sera from four inoculated groups recognized antigens MHP_0513 and MHP_0580. None of the bacterins was able to induce seroconversion against the twelve remaining antigens. This absence of a serological response could be attributed to the lack of antigen expression in M. hyopneumoniae strains used in bacterin production. Additionally the partial protection provided by these vaccines could be due to low expression or misfolding of antigens during vaccine preparation. Therefore, the supplementation of bacterins with these recombinant antigens could be a potential alternative in the development of more effective vaccines.
The current and general safety control tests for vaccines have been the use several animal tests. Vaccine is considered safe if it does not cause weight loss or death in laboratory animals at human dose, does not promote leukocytosis by a factor ⩾10 and showed a Leukopenic toxicity value ⩾80% of the Leukopenic toxicity of the control. The study sets to determine the safety of routine immunization vaccines from Anambra, Ebonyi and Enugu states of Nigeria and indirectly evaluate the efficiency of cold-chain facilities. The study was designed to check the safety of the routine immunization vaccines to the hematopoietic system of mice and mice body weight changes after immunization. Animal body weight changes test showed that the mice immunized with the vaccines increased in weight at days 3 and 7 post-immunization and exceeded 60% weight gain at day 7 post-immunization. None of the mice died during the observation period. Hematopoietic system toxicity tests showed that the vaccines are non- toxic. The vaccines were generally safe and non-toxic. The cold-chain systems in the States studied were efficient and had not compromised the safety of the vaccines.
Toxoplasma gondii is a protozoan parasite that can infect warm-blooded animals including humans. Vaccination studies mostly use tachyzoite specific proteins however in natural route of infection, toxoplasmosis initiates with tissue cysts (bradyzoites) or oocysts (sporozoites) and thereafter stage conversion takes place where the tachyzoites take action and cause acute infection continues with tachyzoites. Despite this knowledge, challenging models used in the vaccination studies prefer administration of tissue cyst forming strains intraperitoneally or subcutaneously instead of oral administration which is the natural route of infection. In the present study, a multivalent adjuvanted recombinant protein vaccine that contains bradyzoite specific BAG1 and tachyzoite specific GRA1 protein and controls were administered to female Swiss Webster outbred mice. Humoral and cellular immune responses were analyzed by Rec-ELISA, Western blot, and flow cytometry. Mice were infected orally with T. gondii PRU strain tissue cysts using feeding needle to mimic the natural route of infection. 40days after challenging microscopy and Real Time PCR were performed to determine the protection level.
•Analysis of PCV13 vaccine efficacy against community-acquired pneumonia in older adults.•Significant difference in disease-free survival in PCV13 recipients compared with placebo.•PCV13 was protective against vaccine-type disease over the 5-year study duration.•No waning of vaccine efficacy was observed.
The results of a serological study examining the antibody responses generated in cats following administration of a trivalent feline vaccine (feline calicivirus [FCV], feline herpesvirus [FHV] and feline panleucopaenia virus [FPV]; Versifel CVR) in combination with an inactivated rabies vaccine, in compliance with European Pharmacopoeia requirements to support new product registrations, are presented.
INTRODUCTION:We conducted a follow-on study to a phase I randomized, controlled trial conducted in Cuba, 2012, to assess the persistence of poliovirus antibodies at 21-22 months following booster dose of Sabin-IPV compared to Salk-IPV in adults who had received multiple doses of oral poliovirus vaccine (OPV) during childhood. METHODS:In 2012, 60 healthy adult males aged 19-23 were randomized to receive one booster dose, of either Sabin-inactivated poliovirus vaccine (Sabin-IPV), adjuvanted Sabin-IPV (aSabin-IPV), or conventional Salk-IPV. In the original study, blood was collected at days 0 (before) and 28 (after vaccination), respectively. In this study, an additional blood sample was collected 21-22 months after vaccination, and tested for neutralizing antibodies to Sabin poliovirus types 1, 2 and 3. RESULTS:We collected sera from 59/60 (98.3%) subjects; 59/59 (100%) remained seropositive to all poliovirus types, 21-22 months after vaccination. The decay curves were very similar among the study groups. Between day 28 and 21-22 months, there was a reduction of ⩾87.4% in median antibody levels for all poliovirus types in all study groups, with no significant differences between the study groups. CONCLUSION:The decay of poliovirus antibodies over a 21-22-month period was similar regardless of the type of booster vaccine used, suggesting the scientific data of Salk IPV long-term persistence and decay may be broadly applicable to Sabin IPV.
Serological memory after inoculation of protective antigen (PA) combined with Alhydrogel adjuvant (PA/Alhydrogel) was examined in New Zealand white rabbits, an animal model for anthrax. A threshold dose of 0.1μg of PA/Alhydrogel was identified which resulted in an ELISA titer 2weeks after a primary immunization of only 0.168μg anti-PA IgG per ml and a toxin-neutralizing antibody titer (TNA ED50) of 1.8 (n=40). A significant increase in anti-PA IgG and TNA ED50 titers were measured (p<0.0001) 2weeks after a booster immunization with 0.1μg of PA/Alhydrogel at 14days (n=10; 40.9μg anti-PA IgG per ml; 522 TNA ED50) and 28days (n=10; 63.8μg anti-PA IgG per ml; 501 TNA ED50). At this threshold dose of PA/Alhydrogel, protection against an aerosol exposure to Bacillus anthracis Ames spores improved as the booster immunization was administered from 4days (40% survival), to 8days (50% survival), and to 12days (80% survival) before challenge. The partial protection of rabbits, even in the absence of protective antibody titers (0.9μg anti-PA IgG per ml and 26 TNA ED50) when the booster immunization was administered 4days before challenge, suggested a protective potential for serologic memory.
The objective of this randomised, controlled, parallel-group monocentric clinical trial was to assess the efficacy (at low and high dose) and the safety (at high dose) of a recombinant canarypox virus (ALVAC®) expressing feline interleukin 2 (IL-2). ALVAC IL-2 was administered to cats as an adjunct treatment of feline fibrosarcoma in complement to surgery and brachytherapy (reference treatment). Seventy-one cats with a first occurrence of feline fibrosarcoma were referred to the Veterinary Oncology Centre for post-surgical radiotherapy. They were randomly assigned to three treatment groups: reference treatment group (23 cats), ALVAC IL-2 low dose group (25 cats) and ALVAC IL-2 high dose group (23 cats). Two dosages of ALVAC IL-2 were used to assess both safety (high dose) and efficacy (high and low doses). The treatment consisted of six consecutive doses of ALVAC IL-2 administered subcutaneously at the tumour site on Day 0 (one day before brachytherapy treatment), Day 7, Day 14, Day 21, Day 35 and Day 49. All cats were evaluated for relapse (i.e. local tumour recurrence and/or metastasis) every three months for at least one year (ALVAC IL-2 high dose group) or two years (reference treatment and ALVAC IL-2 low dose groups) by complete physical examination and regular CT scans. ALVAC IL-2 treatment was well tolerated and adverse effects were limited to mild local reactions. ALVAC IL-2 treatment resulted in a significant longer median time to relapse (>730days in the ALVAC IL-2 low dose group) than in the reference treatment group (287days), and a significant reduction of the risk of relapse by 56% at one year (ALVAC IL-2 treatment groups versus reference treatment group) and 65% at two years (ALVAC IL-2 low dose treatment group versus reference treatment group).
In our previous studies, we discussed the protective efficacy of the two types of vaccine formulation namely SOMVs (single-serotype outer membrane vesicles) and MOMVs (multi-serotype outer membrane vesicles). Here, we compared the immunogenic roles of these two types of formulations and also studied general immunomodulation by Shigella OMVs in adult BALB/c mice. The production of various pro-inflammatory (TNF-α, IL-1β, IL-6, IL-12, IL-18, IFN-γ) and anti-inflammatory (IL-4 and IL-10) cytokine profile were assessed by in vivo, ex vivo and in vitro studies. MOMVs treated mice showed significantly enhanced cytokine production compared to SOMVs treated mice. MOMVs treatment has also upregulated iNOS mRNA synthesis in macrophages. Overall the OMVs of Shigella were found to show a mixed Th1/Th2 response and maintain the balance between pro-inflammation and anti-inflammation in mice. This will be crucial in the development of the next generation OMVs based vaccine against shigellosis.
