The prevention, treatment and control of Haemonchus contortus have been increasingly problematic due to its widespread occurrence and anthelmintic resistance. There are very few descriptions of recombinant antigens being protective for H. contortus, despite the success of various native antigen preparations, including Barbervax. We recently identified an H. contortus excretory–secretory antigen, H. contortus adhesion-regulating molecule 1 (HcADRM1), that served as an immunomodulator to impair host T-cell functions. Given the prophylactic potential of HcADRM1 protein as a vaccine candidate, we hereby assessed the efficacies of HcADRM1 preparations against H. contortus infection. Parasitological and immunological parameters were evaluated throughout all time points of the trials, including fecal egg counts (FEC), abomasal worm burdens, complete blood counts, cytokine production profiles and antibody responses. Active vaccination with recombinant HcADRM1 (rHcADRM1) protein induced protective immunity in inoculated goats, resulting in reductions of 48.9 and 58.6% in cumulative FEC and worm burdens. Simultaneously, passive administration of anti-HcADRM1 antibodies generated encouraging levels of protection with 46.7 and 56.2% reductions in cumulative FEC and worm burdens in challenged goats. In addition, HcADRM1 preparations-immunized goats showed significant differences in mucosal and serum antigen-specific immunoglobulin G (IgG) levels, total mucosal IgA levels, haemoglobin values and circulating interferon-γ, interleukin (IL)-4 and IL-17A production compared to control goats in both trials. The preliminary data of these laboratory trials validated the immunoprophylactic effects of rHcADRM1 protein. It can be pursued as a potential vaccine antigen to develop an effective recombinant subunit vaccine against H. contortus under field conditions.

Soil-transmitted helminths (STHs) collectively infect one fourth of all human beings, and the majority of livestock in the developing world. These gastrointestinal nematodes are the most important parasites on earth with regard to their prevalence in humans and livestock. Current anthelmintic drugs are losing their efficacies due to increasing drug resistance, particularly in STHs of livestock and drug treatment is often followed by rapid reinfection due to failure of the immune system to develop a protective response. Vaccines against STHs offer what drugs cannot accomplish alone. Because such vaccines would have to be produced on such a large scale, and be cost effective, recombinant subunit vaccines that include a minimum number of proteins produced in relatively simple and inexpensive expression systems are required. Here, we summarize all of the previous studies pertaining to recombinant subunit vaccines for STHs of humans and livestock with the goal of both informing the public of just how critical these parasites are, and to help guide future developments. We also discuss several key areas of vaccine development, which we believe to be critical for developing more potent recombinant subunit vaccines with broad-spectrum protection.

Trichinella spiralis is a parasitic helminth that can infect almost all mammals, including humans. Trichinella spiralis infection elicits a typical type 2 immune responses, while suppresses type 1 immune responses, which is in favour of their parasitism. DNA vaccines have been shown to be capable of eliciting balanced CD4+ and CD8+ T cell responses as well as humoral immune responses in small-animal models, which will be advantage to induce protective immune response against helminth infection. In this study, serine protease (Ts-NBLsp) was encoded by a cDNA fragment of new-born T. spiralis larvae, and was inserted after CMV promoter to construct a DNA vaccine [pcDNA3·1(+)-Ts-NBLsp]. Ts-NBLsp expression was demonstrated by immunofluorescence. Sera samples were obtained from vaccinated mice, and they showed strong anti-Ts-NBLsp-specific IgG response. Mice immunized with the pcDNA3·1(+)-Ts-NBLsp DNA vaccine showed a 77·93% reduction in muscle larvae (ML) following challenge with T. spiralis ML. Our results demonstrate that the vaccination with pcDNA3·1(+)-Ts-NBLsp plasmid promoted the balance of type 1 and 2 immune responses and produced a significant protection against T. spiralis infection in mice.

Hepatitis B virus (HBV) vaccination has been part of the Expanded Programme of Immunization (EPI) in Tunisia since 1995. The aim of this study was to evaluate, for the first time, the impact of mass vaccination in Tunisia 17 years after this programme was implemented, and in parallel, assess the long-term persistence of anti-HBs antibody in the vaccinated Tunisian population. A total of 1422 students were recruited (703 vaccinated, 719 non-vaccinated). HBV seromarkers were checked. None of the students from either group had positive HBsAg. The overall prevalence of anti-HBc was 0·8%. A Significantly higher prevalence of anti-HBc was noted in unvaccinated students than in vaccinated (1·4% vs. 0·3%, P = 0·02). The overall seroprotection rate (anti-HBs titre ⩾10 mIU/ml) was 68·9% in vaccinated subjects. Seroprotection rates and geometric mean titres decreased significantly with increasing age, reflecting waning anti-HBs titre over time. No significant difference was detected between seroprotection rates and gender or students’ area of origin. Incomplete vaccination was the only factor associated with an anti-HBs titre <10 mIU/ml. This study demonstrates the excellent efficacy of the HBV vaccination programme in Tunisia 17 years after its launch. However, a significant decline of anti-HBs seroprotection has been observed in ⩾15-year-old adolescents which places them at risk of infection. Additional studies are needed in hyperendemic regions in Tunisia.

Porcine reproductive and respiratory syndrome (PRRS) is an economically important infectious disease of swine. Constant emergence of variant strains of PRRS virus (PPRSV) and virus-mediated immune evasion followed by viral persistence result in increased incidence and recurrence of PRRS in swine herds. Current live and killed PRRSV vaccines administered by a parenteral route are ineffective in inducing complete protection. Thus, new approaches in design and delivery of PRRSV vaccines are needed to reduce the disease burden of the swine industry. Induction of an effective mucosal immunity to several respiratory pathogens by direct delivery of a vaccine to mucosal sites has proven to be effective in a mouse model. However, there are challenges in eliciting mucosal immunity to PRRS due to our limited understanding of safe and potent mucosal adjuvants, which could potentiate the mucosal immune response to PRRSV. The purpose of this review is to discuss methods for induction of protective mucosal immune responses in the respiratory tract of pigs. The manuscript also discusses how PRRSV modulates innate, adaptive and immunoregulatory responses at both mucosal and systemic sites of infected and/or vaccinated pigs. This information may help in the design of innovative mucosal vaccines to elicit superior cross-protective immunity against divergent field strains of PRRSV.

Mechanisms of protective immunity to larvae of Brugia pahangi were studied in congenitally athymic nude C3H/HeN mice and their syngeneic heterozygous littermates. An average 11% if subcutaneous larval inocula was recovered from control nudes 28 days after inoculation. No worms were recovered from nude recipients of viable splenic Thy 1·2+ T lymphocytes from heterozygotes which had killed a priming does of B. pahangi larvae. Primed T lymphocytes, depleted of either Lyt 1·1+of Lyt 2·1+cells or incubated with anti-Thy 1.2 monoclonal antibody and complement, failed to protect nude mic against a larval challenge. Nor were primed B lymphocytes depleted by Thy 1·2+T cell contaminants protective. Treatment with cyclosporin A (CsA) did not increase the numbers of worms recovered from heterozygotes nor did CsA treatment of heterozygous cell donor abolish the ability of primed Thy 1·2+T lymphocytes to transfer protection to nude mice. IgG but not IgM antibody titres to B. pahangi antigens were depressed in all CsA-treated mice. CsA treatment of nude mice had no direct effect upon development of B. pahagi larvae. These results show that ptotective immunity to larvae of B. pahangi in mice depends upon small numbers of Thy 1·2+T cells which are CsA-resistant.

The leucocyte responses in peripheral blood and pulmonary airways are described following vaccination of mice with radiation-attenuated parasites, and subsequent challenge with normal parasites. Percutaneous vaccination stimulated a large and sustained expansion of the circulating lymphocyte pool, more marked than after intradermal vaccination with lung schistosomula which induced comparable levels of resistance. Macrophages and lymphocytes infiltrated the pulmonary airways in response to vaccination by both routes, the lymphocytes being particularly abundant after intradermal vaccination. Exposure of mice to an equivalent number of normal cercariae induced an earlier lymphocytosis of short duration; far fewer macrophages and lymphocytes infiltrated the lungs than after vaccination. An intense but transient pulmonary eosinophilia peaked at 3 weeks after primary exposure to either normal or attenuated parasites. Percutaneous challenge of vaccinated mice elicited higher levels of circulating lymphocytes than challenge of unsensitized controls. However, whilst leucocyte numbers of all cell types were still elevated in the airways at challenge as a consequence of vaccination, no further cellular recruitment was observed coincident with parasite elimination. Our data are compatible with the hypothesis that the mechanism of immunity in once-vaccinated mice involves a T lymphocyte-macrophage interaction triggered by antigen release from lung schistosomula.

Worm expulsion of, and IgE and interferon (IFN)-γ responses to, Nippostrongylus brasiliensis were studied in 2 rat strains, Brown Norway (BN) and Fischer (F)-344. BN rats expelled the majority of worms by day 14 post-infection (p.i.) with approximately 6% of worms surviving for at least 3 weeks. In F-344 rats, worm expulsion was delayed by 2 days relative to that in BN, while the numbers of residual worms were significantly fewer than in BN, suggesting that different immune mechanisms are involved in early and late phases of immunity. Total serum IgE, as well as in vitro IgE production by mesenteric lymph node (MLN) cells, was increased 2 weeks p.i., the levels being markedly higher in BN than in F-344 rats. Serum rat mast cell protease II was also increased more significantly in BN than in F-344 rats. In contrast, production of IgG2a and IFN-γ by MLN and spleen cells was found to be higher in F-344 than in BN rats. These results indicate that the early worm expulsion is correlated with the host IgE and mast cell responsiveness, whereas the persistence of infection in the late period may be controlled by different immune mechanisms.

The radiation-attenuated schistosome vaccine induces a high level of protective immunity in rodents. In order to assess its potential relevance to man, we have tested its efficacy in the non-human primate Papio anubis. A vaccination regime consisting of 3 exposures of approximately 9000 cercariae irradiated with 30 or 60krad. of gamma radiation induced > 50% protection to a challenge with normal larvae. A lower attenuating dose of 20 krad., optimal for vaccination of mice, was less effective. All vaccination regimes elicited a population of PBMC which proliferated in vitro in response to antigen. These responses peaked after the third exposure but were significantly lower after challenge. They revealed relatively little cross-reactivity with adult Schistosoma haematobium antigens and provided some evidence for stage-specific antigens. Circulating IgM reactive with adult S. mansoni antigen was detected after the second vaccination but levels remained low throughout. In contrast, IgG levels were boosted by successive vaccinations, although they showed a tendency to decline from 14 days after each exposure. There also appeared to be a lag of about 14 days after challenge before levels began to rise. Thus, both proliferation and antibody data suggest a lower responsiveness after challenge which may reflect either the reduced antigenic load or immunogenicity of normal, compared to vaccinating larvae. The data indicate that the attenuated schistosome vaccine is capable of inducing protection in a highly permissive primate host, with the implication that the mechanisms involved may also be relevant to man.

This review of protozoan and helminth infections in pregnancy focuses on the impact on the immune response in the newborn infant to maternal infection. Studies of protozoan and helminth infections in pregnant women and in their offspring have shown that children exposed to antigens or microorganisms during pregnancy often have a reduced immune response to these infections. The most common finding is a reduced IFNγ response to specific antigens regardless of specific infection studied. In some studies the impaired immune response disappeared before the age of one year, while in other studies the impaired immune response was present as much as two decades after birth. Data from chronic viral infections like Rubella, cytomegalovirus and hepatitis B also show that congenital or perinatal infections may result in a life-long inability to control the infections. Studies of both helminth and protozoan infections show that children exposed to antigens during gestation have a microorganism-specific impaired immune response which is characterized by reduced IFN-γ and stimulation of responses to specific antigens.

Neospora caninum tachyzoites attenuated through passage in tissue culture were tested for their ability to induce protective immunity against a lethal challenge dose of parasites. Balb/c mice were each inoculated with either 1×106 live virulent tachyzoites (Group 1) or 1×106 live attenuated tachyzoites (Group 2), while (Group 3) received a control inoculum. All mice were each challenged 28 days later with 5×106 virulent parasites. Histopathological lesions in the brains including necrosis and microgliosis were observed following post-mortem on day 28 post-challenge (p.c.) in 71% of Group 1 and 56% of Group 2. Immunohistochemistry (IHC) of these lesions showed tachyzoites and Neospora antigens to be associated with moderate brain lesions in 17% of Group 1, while in 11% of Group 2 N. caninum tissue cysts were detected, but these were not associated with lesions, Parasite DNA was detected by PCR in the brains of 86% of mice in Group 1 and 56% of mice in Group 2. Following challenge the mice in Group 3 showed high morbidity and 100% mortality within 17 days p.c. Positive IHC for N. caninum was seen in 88% of the Group 3 mice and parasite DNA was detected in all brain samples. This study shows that it is possible to protect against a lethal challenge of N. caninum through inoculation with attenuated or virulent tachyzoites. However, more severe pathology developed in mice initially inoculated with virulent parasites following a secondary challenge, compared to mice initially inoculated with attenuated parasites.

The present report compares the macrophage function in rodent hosts susceptible and resistant to the human lymphatic filariid Brugia malayi. Macrophages from both mastomys (resistant) and gerbil (susceptible) infected intraperitoneally (i.p.) with the infective larvae (L3) of B. malayi were isolated from peritoneal lavage at different time-intervals and formation rate of NO, H2O2, O2−, TNF-α, glutathione peroxidase and reductase was assayed. NO release was found to be significantly increased in resistant mastomys as compared to gerbils and the release was markedly suppressed by i.p. administration of the NOS inhibitor aminoguanidine (AG). The AG-treated mastomys also demonstrated significantly greater establishment of larvae which correlated well with suppressed formation of NO. Nitric oxide synergizes with superoxide to form peroxynitrite radical (potent oxidant), which is known to be more toxic per se than NO. Results indicate the possible involvement of peroxynitrite in the rapid killing of larvae in the peritoneal cavity of mastomys. In contrast, the production of H2O2 was found to be enhanced in both species indicating that B. malayi L3 could withstand the toxic effects of H2O2. The higher level of glutathione peroxidase and reductase, as observed in mastomys compared with the gerbil after larval introduction, possibly protects the cell against the injurious effect of H2O2. The TNF-α level remained virtually unchanged in both the hosts, suggesting an insignificant role for this cytokine in parasite establishment.

Immune responses that kill pathogens or reduce their reproductive rate are generally important in protecting hosts from infection and disease. Pathogens that escape the full impact of such responses will survive, and any heritable genetic basis of this evasion will be selected. Due to the memory component of vertebrate immune responses, pathogens with rare alleles of a target antigen can have an advantage over those with common alleles, leading to the maintenance of a polymorphism. At the genetic level, there ought to be detectable signatures of balancing selection in the genes encoding these antigens. Here, methods for identifying these selective signatures are reviewed. Their practical utility for identifying which antigens are targets of protective immune responses is discussed.