Post-exposure Vaccination Research Articles

Immunogenic potential of latency associated antigens against Mycobacterium tuberculosis

Tuberculosis remains a great health threat to the world among infectious diseases particularly with the advent of human immunodeficiency virus and emergence of drug resistant strains. In the light of the inconsistent efficacy imparted by the only currently available pre-exposure vaccine bacillus Calmette–Guerin BCG, the development of an improved TB vaccine is a very high international research priority. Vaccine candidates currently in clinical trials are also pre-exposure vaccines that aim to prevent active tuberculosis during an individual's lifetime. According to World Health Organization approximately a third of the world's population is latently infected with Mycobacterium tuberculosis. Dormancy or latency of Mycobacteria is associated with the formation of granuloma with poorly perfused interior leading to expression of genes which help them survive in this hostile environment. A group of about 50 genes belonging to the DosR regulon also known as latency antigens are expressed by Mycobacteria when they are persisting in the immuno-competent host. An understanding of the immunological effects produced by products of these latency induced genes may help in making a more potent vaccine. Incorporation of latency antigens into improved (live or subunit) vaccines may enhance the impact of these vaccines in which BCG priming can be followed by multisubunit protein boosting. These vaccines could act as post exposure vaccines for containment and prevention of latent TB activation. This heterologous boosting of BCG-primed immunity will be able to stimulate the known immune correlates of protective immunity against M. tuberculosis i.e. TH1 cells (CD4+ and CD8+ T cells) mediated immune responses with cytokines such as IFN-γ and TNF-α⋅ In our review we have analysed and compared the immunogenic potential of various latency-associated antigens of the DosR regulon in line with the current strategy of developing a recombinant post exposure booster vaccine.

Use of a recombinant vaccinia virus expressing interferon gamma for post-exposure protection against vaccinia and ectromelia viruses.

Post-exposure vaccination with vaccinia virus (VACV) has been suggested to be effective in minimizing death if administered within four days of smallpox exposure. While there is anecdotal evidence for efficacy of post-exposure vaccination this has not been definitively studied in humans. In this study, we analyzed post-exposure prophylaxis using several attenuated recombinant VACV in a mouse model. A recombinant VACV expressing murine interferon gamma (IFN-γ) was most effective for post-exposure protection of mice infected with VACV and ectromelia virus (ECTV). Untreated animals infected with VACV exhibited severe weight loss and morbidity leading to 100% mortality by 8 to 10 days post-infection. Animals treated one day post-infection had milder symptoms, decreased weight loss and morbidity, and 100% survival. Treatment on days 2 or 3 post-infection resulted in 40% and 20% survival, respectively. Similar results were seen in ECTV-infected mice. Despite the differences in survival rates in the VACV model, the viral load was similar in both treated and untreated mice while treated mice displayed a high level of IFN-γ in the serum. These results suggest that protection provided by IFN-γ expressed by VACV may be mediated by its immunoregulatory activities rather than its antiviral effects. These results highlight the importance of IFN-γ as a modulator of the immune response for post-exposure prophylaxis and could be used potentially as another post-exposure prophylaxis tool to prevent morbidity following infection with smallpox and other orthopoxviruses.

Evaluation of hepatitis A vaccine in post-exposure prophylaxis, The Netherlands, 2004-2012.

BackgroundThe secondary attack rate of hepatitis A virus (HAV) among contacts of cases is up to 50%. Historically, contacts were offered immunoglobulin (IG, a human derived blood product) as post-exposure prophylaxis (PEP). Amid safety concerns about IG, HAV vaccine is increasingly recommended instead. Public health authorities’ recommendations differ, particularly for healthy contacts ≥40 years old, where vaccine efficacy data is limited. We evaluated routine use of HAV vaccine as an alternative to immunoglobulin in PEP, in those considered at low risk of severe infection in the Netherlands.MethodsHousehold contacts of acute HAV cases notified in Amsterdam (2004-2012) were invited ≤14 days post-exposure, for baseline anti-HAV testing and PEP according to national guidelines: immunoglobulin if at risk of severe infection, or hepatitis A vaccine if healthy and at low risk (aged <30, or, 30-50 years and vaccinated <8 days post-exposure). Incidence of laboratory confirmed secondary infection in susceptible contacts was assessed 4-8 weeks post-exposure. In a vaccinated subgroup, relative risk (RR) of secondary infection with estimated using Poisson regression.ResultsOf 547 contacts identified, 191 were susceptible to HAV. Per-protocol, 167 (87%) were vaccinated (mean:6.7 days post-exposure, standard deviation(sd)=3.3) and 24 (13%) were given immunoglobulin (mean:9.7 days post-exposure, sd=2.8). At follow-up testing, 8/112 (7%) had a laboratory confirmed infection of whom 7 were symptomatic. All secondary infections occurred in vaccinated contacts, and half were >40 years of age. In healthy contacts vaccinated per-protocol ≤8 days post-exposure, RRref. ≤15 years of secondary infection in those >40 years was 12.0 (95%CI:1.3-106.7).ConclusionsTimely administration of HAV vaccine in PEP was feasible and the secondary attack rate was low in those <40 years. Internationally, upper age-limits for post-exposure vaccination vary. Pending larger studies, immunoglobulin should be considered PEP of choice in people >40 years of age and those vulnerable to severe disease.

Survey of animal bite injuries and their management for an estimate of human rabies deaths in N’Djaména, Chad

To estimate the annual human rabies incidence as a baseline prior to mass dog vaccination campaigns in N'Djaména, Chad. Survey of animal bites, involving 50% of all healthcare providers in N'Djaména, from September 2008 to April 2009. Of 86 people exposed to a suspected rabid animal, 50% received post-exposure vaccination and a further 8% had their wound cleaned. We estimated annual incidence of bites from suspected rabid animals of 12.9/100,000 and an incidence of 0.7 human rabies deaths/100,000, resulting in 7 estimated deaths (95% confidence interval 4-10 deaths) per year in N'Djaména. 14% of bite victims sought help from veterinarians. Closer cooperation between physicians and veterinarians warrants more effective rabies control. The high proportion (42%) of potentially exposed people without post-exposure vaccination or wound treatment necessitates urgent attention.

Therapeutic vaccination against relevant high virulence clinical isolates of Mycobacterium tuberculosis

The purpose of this study was to attempt to develop therapeutic or post-exposure vaccines that could slow progressive disease in guinea pigs infected by low dose aerosol with very high virulence Beijing isolates of Mycobacterium tuberculosis, currently classified as Category C biodefense pathogens by the NIH and CDC. After screening several candidates we focused on the use of three candidates; these were a pool of bacterial iron acquisition proteins, a pool of antigens recognized by T cells from chronically infected mice thought to represent proteins made by the bacillus in response to decreases in local oxygen tension, and a bacterial lipoprotein that is a potent TLR2 agonist. When delivered in a potent GLA-based adjuvant [targeting TLR4 and TLR9], in most cases we were unable to reduce the bacterial load in the lungs. However, the pathologic appearance of lungs from these animals showed that, while primary lesions were most unaffected and had become necrotic, the development of large, lung consolidating secondary lesions seemed to have been mostly prevented. In animals given both a priming vaccination and a boost the effects were prominent, and almost certainly contributed to significantly prolonged survival in these animals. In a biodefense situation, this prolonged survival would be potentially long enough to allow for the organism to be identified and a drug susceptibility profile determined.

Vaccine development for tuberculosis: current progress.

Very substantial efforts have been made over the past decade or more to develop vaccines against tuberculosis. Historically, this began with a view to replace the current vaccine, Bacillus Calmette Guérin (BCG), but more recently most candidates are either new forms of this bacillus, or are designed to boost immunity in children given BCG as infants. Good progress is being made, but very few have, as yet, progressed into clinical trials. The leading candidate has advanced to phase IIb efficacy testing, with disappointing results. This article discusses the various types of vaccines, including those designed to be used in a prophylactic setting, either alone or BCG-boosting, true therapeutic (post-exposure) vaccines, and therapeutic vaccines designed to augment chemotherapy. While there is no doubt that progress is still being made, we have a growing awareness of the limitations of our animal model screening processes, further amplified by the fact that we still do not have a clear picture of the immunological responses involved, and the precise type of long-lived immunity that effective new vaccines will need to induce.

B Cell Infection and Activation by Rabies Virus-Based Vaccines

Replication-deficient rabies viruses (RABV) are promising rabies postexposure vaccines due to their prompt and potent stimulation of protective virus neutralizing antibody titers, which are produced in mice by both T-dependent and T-independent mechanisms. To promote such early and robust B cell stimulation, we hypothesized that live RABV-based vaccines directly infect B cells, thereby activating a large pool of antigen-presenting cells (APCs) capable of providing early priming and costimulation to CD4(+) T cells. In this report, we show that live RABV-based vaccine vectors efficiently infect naive primary murine and human B cells ex vivo. Infection of B cells resulted in the significant upregulation of early markers of B cell activation and antigen presentation, including CD69, major histocompatibility complex class II (MHC-II), and CD40 in murine B cells or HLA-DR and CD40 in human B cells compared to mock-infected cells or cells treated with an inactivated RABV-based vaccine. Furthermore, primary B cells infected with a live RABV expressing ovalbumin were able to prime and stimulate naive CD4(+) OT-II T cells to proliferate and to secrete interleukin-2 (IL-2), demonstrating a functional consequence of B cell infection and activation by live RABV-based vaccine vectors. We propose that this direct B cell stimulation by live RABV-based vaccines is a potential mechanism underlying their induction of early protective T cell-dependent B cell responses, and that designing live RABV-based vaccines to infect and activate B cells represents a promising strategy to develop a single-dose postexposure rabies vaccine where the generation of early protective antibody titers is critical.

Reinvestigating the role of IgM in rabies virus postexposure vaccination.

B cells secreting IgG antibodies, but not IgM, are thought to be solely responsible for vaccine-induced protection against rabies virus (RABV) infections in postexposure settings. In this report, we reinvestigated the potential for IgM to mediate protection in a mouse model of RABV vaccination. Immunocompetent mice immunized with an experimental live replication-deficient RABV-based vaccine produced virus neutralizing antibodies (VNAs) within 3 days of vaccination. However, mice unable to produce soluble IgM (sIgM(-/-)) did not produce VNAs until 7 days postimmunization. Furthermore, sIgM(-/-) mice were not protected against RABV infection when challenged 3 days postimmunization, while all wild-type mice survived challenge. Consistent with the lack of protection against pathogenic RABV challenge, approximately 50- to 100-fold higher viral loads of challenge virus were detected in the muscle, spinal cord, and brain of immunized sIgM(-/-) mice compared to control mice. In addition, IgG antibody titers in vaccinated wild-type and sIgM(-/-) mice were similar at all time points postimmunization, suggesting that protection against RABV challenge is due to the direct effects of IgM and not the influence of IgM on the development of effective IgG antibody titers. In all, early vaccine-induced IgM can limit dissemination of pathogenic RABV to the central nervous system and mediate protection against pathogenic RABV challenge. Considering the importance for the rapid induction of VNAs to protect against RABV infections in postexposure prophylaxis settings, these findings may help guide the development of a single-dose human rabies vaccine.

The influence of familial factors on post rabies exposure vaccination in rural habitats

To understand the current situation of potential exposure to rabies among the rural habitats in Hunan province, and to study the impact related to familial factors on post rabies exposure vaccination. In total, 40 villages from 20 townships of 4 counties were selected by multistage sampling method. Study samples were selected from these villagers and familial basic information and vaccination post rabies exposures were recorded through questionnaires. Data were statistically analyzed by SPSS 17.0. Among 3042 villagers from 864 households being surveyed, 124 person-time exposures were found from January, 2009 to October, 2010, with a total exposure rate as 4.08%, and the annual average exposure rate as 2.33%. Data from univariate analysis showed that the rates on post rabies exposure vaccination were statistically correlated with the following four factors:knowledge on the score of rabies prevention (χ(2) = 8.260, P = 0.042), whether being involved in the new type of rural cooperative medical care(P = 0.035), family disposable cash income in the year of 2009(χ(2) = 10.831, P = 0.031), distance between the households and the health facilities in towns and townships(χ(2) = 9.071, P = 0.033). Results from logistic regression analysis indicated that the score of knowledge on rabies prevention(O∧R = 1.420, 95% CI:1.055-1.905)and the annual disposable cash income of the family in 2009(O∧R = 1.480, 95% CI:1.044-2.098)were independent factors that influencing the rabies vaccination. Strengthening the education programs on rabies prevention in rural habitats and increasing family income were feasible way to increase the rate of rabies vaccination in rural areas of Hunan province.

Evaluation of Immunogenicity and Efficacy of Anthrax Vaccine Adsorbed for Postexposure Prophylaxis

Antimicrobials administered postexposure can reduce the incidence or progression of anthrax disease, but they do not protect against the disease resulting from the germination of spores that may remain in the body after cessation of the antimicrobial regimen. Such additional protection may be achieved by postexposure vaccination; however, no anthrax vaccine is licensed for postexposure prophylaxis (PEP). In a rabbit PEP study, animals were subjected to lethal challenge with aerosolized Bacillus anthracis spores and then were treated with levofloxacin with or without concomitant intramuscular (i.m.) vaccination with anthrax vaccine adsorbed (AVA) (BioThrax; Emergent BioDefense Operations Lansing LLC, Lansing, MI), administered twice, 1 week apart. A significant increase in survival rates was observed among vaccinated animals compared to those treated with antibiotic alone. In preexposure prophylaxis studies in rabbits and nonhuman primates (NHPs), animals received two i.m. vaccinations 1 month apart and were challenged with aerosolized anthrax spores at day 70. Prechallenge toxin-neutralizing antibody (TNA) titers correlated with animal survival postchallenge and provided the means for deriving an antibody titer associated with a specific probability of survival in animals. In a clinical immunogenicity study, 82% of the subjects met or exceeded the prechallenge TNA value that was associated with a 70% probability of survival in rabbits and 88% probability of survival in NHPs, which was estimated based on the results of animal preexposure prophylaxis studies. The animal data provide initial information on protective antibody levels for anthrax, as well as support previous findings regarding the ability of AVA to provide added protection to B. anthracis-infected animals compared to antimicrobial treatment alone.

Investigation on a Dog Rabies Case and Rabid Dog Meat Consumption, Nakhon Phanom Province, Thailand, 2011

In March 2011, public fear on health risk of rabid dog meat consumption was emerged in Nakhon Phanom Province. Investigation was conducted to identify extent of exposure and recommendation for rabies prevention. We surveyed in affected villages to find out rabies cases and exposed contacts among dogs, cats and humans. Persons who had contacted with the rabid dog, its carcass or meat were interviewed about their contacts, knowledge, attitudes and practices (KAP) towards rabies. The survey revealed that three owned dogs had been bitten by the rabid dog and 58 persons contacted it. Among the contact persons, 11.3% (bitten by the rabid dog, contact with carcass or saliva, butchered or cooked) and 19.0% (contacted dogs bitten by the rabid dog) fit in the WHO criteria as exposed and possible exposed persons respectively. Thirty two persons who ate well cooked meat of the rabid dog were classified as non-exposed persons. One third of the contact persons did not know about rabies. Persons who ate rabid dog meat had less knowledge on rabies reservoir and transmission compared with those did not eat (P-value &lt;0.05). Contact persons and dogs were provided with post-exposure vaccination; none of them developed rabies. Several types of exposure, except ingesting well cooked meat, posed risk of rabies and local public should be educated about these for better personal protective practices.

Post-exposure vaccination with MP-12 lacking NSs protects mice against lethal Rift Valley fever virus challenge

Rift Valley fever virus (RVFV) causes severe disease in humans and livestock. There are currently no approved antivirals or vaccines for the treatment or prevention of RVF disease in humans. A major virulence factor of RVFV is the NSs protein, which inhibits host transcription including the interferon (IFN)-β gene and promotes the degradation of dsRNA-dependent protein kinase, PKR. We analyzed the efficacy of the live-attenuated MP-12 vaccine strain and MP-12 variants that lack the NSs protein as post-exposure vaccinations. Although parental MP-12 failed to elicit a protective effect in mice challenged with wild-type (wt) RVFV by the intranasal route, significant protection was demonstrated by vaccination with MP-12 strains lacking NSs when they were administered at 20–30min post-exposure. Viremia and virus replication in liver, spleen and brain were also inhibited by post-exposure vaccination with MP-12 lacking NSs. The protective effect was mostly lost when vaccination was delayed 6 or 24h after intranasal RVFV challenge. When mice were challenged subcutaneously, efficacy of MP-12 lacking NSs was diminished, most likely due to more rapid dissemination of wt RVFV. Our findings suggest that post-exposure vaccination with MP-12 lacking NSs may be developed as a novel post-exposure treatment to prevent RVF.

Postexposure Subunit Vaccination against Chronic Enteric Mycobacterial Infection in a Natural Host

The control of chronic bacterial diseases with high prevalence in areas of endemicity would strongly benefit from availability of postexposure vaccines. The development of these vaccines against mycobacterial infections, such as (para)tuberculosis, is hampered by lack of experience in natural hosts. Paratuberculosis in cattle is both a mycobacterial disease of worldwide importance and a natural host model for mycobacterial infections in general. The present study showed beneficial effects of therapeutic heat shock protein 70 (Hsp70) vaccination in cattle with naturally acquired chronic infection with Mycobacterium avium subsp. paratuberculosis. Vaccination-induced protection was associated with antibody responses, rather than with induction of specific T helper 1 cells. Targeted therapeutic postexposure vaccination complementary to selective use of antibiotics could be an effective approach for control of chronic mycobacterial infections.

Rabies neutralizing antibody after 2 intradermal doses on days 0 and 21 for pre-exposure prophylaxis

Pre-exposure prophylaxis is recommended for people who will be exposed to rabies virus in the laboratory or who will contact with mammals. World Health Organization recommends 2 doses of a cell-culture rabies vaccine given 1 week apart, and a third booster dose given 2–3 weeks later. Neutralizing antibody response is virtually 100%, and the individual remains sensitized indefinitely. Intradermal pre-exposure regimen for rabies prophylaxis is more economical compared with the conventional intramuscular regimen in terms of vaccine volume. However, both regimens require three clinic visits. In order to reduce non-medical expenses such as transportation to the clinics and to increase compliance, the immunogenicity and safety of two-visit intradermal regimen for pre-exposure prophylaxis were studied. Fifty-five healthy subjects aged between 18 and 24 years were enrolled and divided into two groups. Group A (n=39) received 0.1ml of purified Vero cell rabies vaccine (PVRV; Sanofi Pasteur, Lyon, France; Lot no. Z0996 with an antigenic value of 4.8IU/0.5ml vial) intradermally each at two sites on days 0 and 21. Group B (n=16) received 0.5ml of PVRV intramuscularly on days 0, 7 and 21, as conventional intramuscular regimen for pre-exposure prophylaxis. Rabies neutralizing antibody (Nab) titers were measured on days 0, 35, 365 and 379 (14 days after simulated post-exposure booster vaccination). All subjects from two groups had Nab titers ≥0.5IU/ml on day 35. In addition, the difference between geometric mean titers for group A (4.51IU/ml; range of Nab titers 1.69–13.0IU/ml) and group B (6.74IU/ml; range of Nab titers 2.20–14.23IU/ml) on day 35 was not statistically significant (p>0.05). One year after pre-exposure vaccination, all subjects in both groups received simulated post-exposure booster vaccination with 0.1ml of PVRV ID on days 0 and 3 (day 365 and day 368 after pre-exposure vaccination). After simulated booster vaccinations with 0.1ml PVRV ID on days 0 and 3, all subjects in groups A (GMT 14.38IU/ml; range 2.99–308.44IU/ml) and in group B (GMT 14.06IU/ml; range 3.12–62.09IU/ml) had rabies Nab titers ≥0.5IU/ml on day 14 post-booster (p>0.05). Mild local adverse events such as pain at injection site, pruritus and erythema were observed. Our study indicated that 2-site intradermal pre-exposure regimen on days 0 and 21 with 0.1ml of cell-culture rabies vaccine is safe and immunogenic as the conventional intramuscular regimen.

Laboratory Diagnosis of Human Rabies: Recent Advances

Rabies, an acute progressive, fatal encephalomyelitis, transmitted most commonly through the bite of a rabid animal, is responsible for an estimated 61,000 human deaths worldwide. The true disease burden and public health impact due to rabies remain underestimated due to lack of sensitive laboratory diagnostic methods. Rapid diagnosis of rabies can help initiate prompt infection control and public health measures, obviate the need for unnecessary treatment/medical tests, and assist in timely administration of pre- or postexposure prophylactic vaccination to family members and medical staff. Antemortem diagnosis of human rabies provides an impetus for clinicians to attempt experimental therapeutic approaches in some patients, especially after the reported survival of a few cases of human rabies. Traditional methods for antemortem and postmortem rabies diagnosis have several limitations. Recent advances in technology have led to the improvement or development of several diagnostic assays which include methods for rabies viral antigen and antibody detection and assays for viral nucleic acid detection and identification of specific biomarkers. These assays which complement traditional methods have the potential to revolutionize rabies diagnosis in future.

Rabies prevention in people who travel overseas

Increasing numbers of U.K. travellers are visiting rabies-endemic countries. This article describes how this invariably fatal disease is transmitted to humans and how it may be prevented by increased awareness, and pre and post-exposure vaccination. It aims to help practitioners identify patients at increased risk of rabies, and looks at the common myths and misconceptions travellers may have about rabies and rabies vaccination.

Management and Control of Varicella on Cruise Ships: A Collaborative Approach to Promoting Public Health

In most years varicella is the vaccine-preventable disease most frequently reported to Centers for Disease Control and Prevention (CDC) by cruise ships. Since 2005, CDC has received numerous isolated case reports of varicella among crew members and has investigated varicella outbreaks aboard vessels sailing into and from US seaports. CDC investigators reviewed electronic varicella case reports from 2005 to 2009 and outbreak reports from 2009 to characterize the response and control efforts implemented by cruise ships in accordance with CDC protocols. Outbreak reports from 2009 were manually reviewed for details of case identification, contact investigations, isolation and restriction of cases and contacts, respectively, and number of contacts administered varicella vaccine post-exposure by cruise lines. During 2005 to 2009, cruise ships reported 278 cases of varicella to CDC among predominantly male (80%) crew members, three-quarters of whom were residents of Caribbean countries, Indonesia, the Philippines, or India, and whose median age was 29 years. Cases were more commonly reported during spring and winter months. During 2009, cruise ships reported 94 varicella cases among crew members of which 66 (70%) were associated with 18 reported varicella outbreaks. Outbreak response included isolation of 66 (100%) of 66 cases, restriction of 66 (26%) of 255 crew-contacts, and administration of post-exposure vaccine to 522 close contacts and other susceptible crew members per standard CDC recommendations. Most cases reported to CDC during 2005 to 2009 were among non-US resident crew members. Overall, cruise lines sailing into North America have the onboard capability to manage varicella cases and outbreaks and appear responsive to CDC recommendations. Cruise lines should continue to implement CDC-recommended response protocols to curtail outbreaks rapidly and should consider whether pre-placement varicella immunity screening and vaccination of crew members is a cost-effective option for their respective fleet operations.

Novel approaches toward the development of an oral post-exposure DNA vaccine for latent tuberculosis using Salmonella typhimurium ∆aroA vector

Tuberculosis remains one of the major causes of global public health problems. There is no effective vaccine for the disease until now. Many reports show that DNA vaccines are promising to induce protection against Mycobacterium tuberculosis (M. tb); however, the efficiency of DNA vaccine is limited due to inadequate delivery systems. Among others, live attenuated bacterial vectors such as Salmonella enterica typhimurium ( S. typhimurium ) have significant promise as efficient mucosal delivery vehicles for DNA vaccines. In this study, we constructed recombinant attenuated S. typhimurium DNA vaccines carrying genes encoding resuscitation promoting factor (Rpf)-like proteins of M. tb on eukaryotic expression plasmid agianst latent tuberculosis and evaluated the plasmid stability and growth curve assays of the recombinant Salmonella vaccine constructs in vitro. Four Rpf gene fragments (RpfB, RpfC, RpfD, RpfE) associated with latency were amplified from genomic DNA of the H37Rv strain of M. tb, cloned into eukaryotic expression plasmid (pVR1020) and verified by sequencing. In later studies, we will demonstrate the potential use of the Salmonella -mediated DNA constructs as candidate post-exposure vaccines against tuberculosis through testing their immunogenicity and effectiveness for oral delivery in eukaryotic systems. Key words : Latent tuberculosis, resuscitation promoting factor (Rpf), DNA vaccine, recombinant Salmonella typhimurium.

Procedures for prevention of rabies in Slovenia

Background: In spite of many years’ suppression, the rabies is still present worldwide and as a consequence poses a risk for human infection. A review of the system and evaluation of the efficacy of procedures performed by veterinary and health services for the prevention of rabies in Slovenia were carried out. Methods: Using retrospective investigation, the following data were analyzed: number of laboratory confirmed rabid animals (in the period from 1980 to 2009) and number of persons treated in antirabies outpatient departments, number of post-exposure vaccinated persons and number of persons that received human rabies immunoglobulin (in the period from 1992 to 2009). Results: Vaccination of foxes by dumping baits from the planes in Slovenia started in the year 1995. After that, the number of rabid wild animals decreased rapidly. In spite of that, the reduction of rabid animals has only limited influence on the post-exposure treatment of people. In the period 1992–2009 the number of treated persons ranged from 2681 to 4434 per year and declined over the years. The decision for the post-exposure vaccination of treated persons against rabies was made in 21.6 % of cases and for the application of human rabies immunoglobulin in 6.7 % of vaccinated persons. In 64 % of cases the postexposure vaccination was necessary owing to the bites caused by a dog of an unknown owner. Conclusion: As a result of good cooperation between veterinary and health services, Slovenia has been free of human rabies for 60 years. But nevertheless, we have not been able to eradicate the animal rabies yet. Because of great migration of people and animals there is also a permanent risk of imported rabies. The prevention of rabies must be continued with proven effective procedures.

Editorial Commentary: Rabies Postexposure Vaccination: Are Antibody Responses Adequate?

responses are expected to result in titers >0.5 IU/mL on day 14 and to remain detectable for at least 1 year. Studies have also shown that World Health Organization (WHO)–recognized tissue culture rabies vaccines will maintain detectable levels of antibody for at least 21 years in most healthy subjects [2]. Receipt of intramuscular or intradermal boosters is expected to result in a rapidly accelerated antibody response that eliminates the need for immunoglobulin. We are aware of very rare cases of poor response to rabies vaccination in hosts who appeared to be healthy. A laboratory technician who was expected to work with rabies virus was found to be a nonresponder and had to be shifted to another position when several boosters failed to induce antibody (G. M. Baer, personal communication). Very poor or no response to preexposure and postexposure rabies vaccination has been well documented in human immunodeficiency virus (HIV)–infected subjects [3] and is very likely with immunosuppressive drugs; though definitive studies are lacking. Poor or no responses to other vaccines, particularly hepatitis B virus vaccine, are also known [4] and are