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PubMed1989

Prospects for the total eradication of rinderpest.

Rinderpest, a major economic problem of Africa and Asia, is a highly contagious viral disease of cattle and buffalo with greater than 90% mortality in susceptible herds. We have developed an effective vaccinia virus recombinant vaccine for rinderpest which protects cattle against challenge by more than 1000 times the lethal dose of the virus. The vaccine circumvents the major logistical problems of the Plowright tissue culture vaccine that occasioned previous failures to eradicate rinderpest by vaccination. The recombinant can easily be propagated and administered by scarification, using methods employed in the world-wide eradication of smallpox. More importantly, the lyophilized form of vaccinia virus is thermostable and does not require maintenance of the cold chain, a distinct advantage in the hot and arid regions of Africa and Asia.

Animals↗

PubMed1992

Heat stability of a recombinant DNA hepatitis B vaccine.

The heat stability of a recombinant DNA hepatitis B vaccine was studied in healthy adult volunteers. When compared with vaccine stored at 4 degrees C, heating of the vaccine for 1 week at 45 degrees C or for 1 month at 37 degrees C did not alter the reactogenicity or the ability of the vaccine to elicit antibody titres considered to be protective. These results have significance in situations where the cold chain is broken, as can happen in countries where proper storage and transport facilities are not always available.

Adolescent↗

PubMed1994

Human immunization in developing countries: practical and theoretical problems and prospects.

While measles, pertussis and tetanus were responsible during the early 1990s for nearly two million deaths in developing countries, no deaths were attributable to them in industrialized countries. More than 96% of global deaths by communicable diseases were also from developing countries. Respiratory infections ranked first in communicable morbidity at all ages. Even though vaccines of bacterial or viral origin or a prophylactic for passive immunization are produced in 24, 16 and 15 developing countries, respectively, none of the developing countries manufactures a plasma-derived prophylactic or biological response modifier. Nearly every country relies on import of one or more vaccines. The suboptimal performance of otherwise meritorious products has been due to faulty vaccine administration practices. Expanding populations, poverty and lack of education, cold-chain defects, and inadequate facilities for transport of vaccines to target populations in remote areas have been responsible for the poor performance of vaccines in the community. Mounting foreign debts and budgetary strains resulting from the care and prevention of AIDS/HIV have considerably strained national and international efforts to offer routine vaccinations in childhood and pregnancy. This dismal situation could be tackled through research to obtain environmentally stable products for prophylactic use and monoclonal antibody formulations for passive immunization, and through international financial and technical support. All countries should exercise some technical control of the quality of imported and indigenous vaccines during their use for curative or prophylactic purposes. The involvement of private clinicians in immunizations would strengthen national efforts for control of communicable diseases including AIDS, but this is not enough if the local factors cited above are not improved.

Bacterial Vaccines↗

PubMed1995

Stabilising oral poliovaccine at high ambient temperatures.

The oral poliovaccine strains lose infectivity when they are stored above refrigerator temperatures. These losses increase rapidly at the high temperatures encountered in tropical countries, thus causing problems if the cold chain is inadequate. Attempts to minimise these losses have generally relied on the addition of salts such as MgCl2. In this paper we show that the fall in infectivity, which is due to the hydrolysis of the genomic RNA by the RNA polymerase within the virus particle, can be greatly inhibited by the suppression of this enzymatic activity. This can be achieved simply by reducing the pH below 7.

DNA-Directed RNA Polymerases↗

PubMed1990

The serological response to a thermostable Vero cell-adapted rinderpest vaccine under field conditions in Niger.

A lyophilized thermostable Vero cell-adapted ringerpest vaccine, stabilized with lactalbumin hydrolysate and sucrose, was tested for safety, serological response and suitability for use with an abbreviated cold chain under field conditions in Niger. A total of 480 cattle, 90 goats and 55 sheep of unknown serological status were vaccinated on government ranches and observed for at least 22 days. No untoward effects of the vaccine were detected. The serological response to the vaccine stored at environmental temperatures for 30 to 34 days was determined in 144 previously unvaccinated yearling calves. Seroconversion was demonstrated in 98% of the yearling calves using seroneutralization. The un-refrigerated vaccine retained a titer of 3.69 log10 TCID50 per dose through day 34.

Animals↗

PubMed2005

Bacterial ghosts as antigen delivery vehicles.

The bacterial ghost system is a novel vaccine delivery system unusual in that it combines excellent natural intrinsic adjuvant properties with versatile carrier functions for foreign antigens. The efficient tropism of bacterial ghosts (BG) for antigen presenting cells promotes the generation of both cellular and humoral responses to heterologous antigens and carrier envelope structures. The simplicity of both BG production and packaging of (multiple) target antigens makes them particularly suitable for use as combination vaccines. Further advantages of BG vaccines include a long shelf-life without the need of cold-chain storage due to their freeze-dried status, they are safe as they do not involve host DNA or live organisms, they exhibit improved potency with regard to target antigens compared to conventional approaches, they are versatile with regards to DNA or protein antigen choice and size, and as a delivery system they offer high bioavailability.

Adjuvants, Immunologic↗

PubMed2006

Needle-free vaccine delivery.

The search for methods of vaccine delivery not requiring a needle and syringe has been accelerated by recent concerns regarding pandemic disease, bioterrorism, and disease eradication campaigns. Needle-free vaccine delivery could aid in these mass vaccinations by increasing ease and speed of delivery, and by offering improved safety and compliance, decreasing costs, and reducing pain associated with vaccinations. In this article, we summarize the rationale for delivery of needle-free vaccines and discuss several methods currently in use and under development, focusing on needle-free injection devices, transcutaneous immunization, and mucosal immunization. Jet injectors are needle-free devices that deliver liquid vaccine through a nozzle orifice and penetrate the skin with a high-speed narrow stream. They generate improved or equivalent immune responses compared with needle and syringe. Powder injection, a form of jet injection using vaccines in powder form, may obviate the need for the "cold chain." Transcutaneous immunization involves applying vaccine antigen and adjuvant to the skin, using a patch or "microneedles," and can induce both systemic and mucosal immunity. Mucosal immunization has thus far been focused on oral, nasal, and aerosol vaccines. Promising newer technologies in oral vaccination include using attenuated bacteria as vectors and transgenic plant "edible" vaccines. Improved knowledge regarding the immune system and its responses to vaccination continues to inform vaccine technologies for needle-free vaccine delivery.

Administration, Topical↗

PubMedDate not supplied

High correlation of human immunodeficiency virus type-1 viral load measured in dried-blood spot samples and in plasma under different storage conditions.

BACKGROUND: To measure HIV-1 RNA concentration requires venous extraction of blood, use of RNAase-free materials, and transport in a cold chain, which makes difficult the management of samples in developing countries. We evaluated the utility of the determination of HIV-1 RNA concentration in blood samples dried on filter paper (DBS) and subjected to different conditions, as contrasted with determination in plasma. METHODS: HIV-1 RNA concentration was determined in HIV-infected patients in DBS and in plasma samples. Samples were subjected to the following: DBS were stored at 4, 22, and 37 degrees C for 1, 3, and 7 days; samples from patients from four regions of Mexico were mailed to a reference laboratory; DBS were sent under environmental conditions; and plasma samples were sent frozen. HIV-1 RNA concentrations were determined by NucliSens in DBS and by Amplicor test in plasma. RESULTS: HIV-1 RNA concentration determined in DBS subjected to different temperatures and times had a significant correlation (r=0.99) with those obtained in plasma. When compared with values in plasma, Kappa agreement coefficients of values in DBS stored for 7 days at 4, 22, and 37 degrees C were 0.98, 0.83, and 0.94, respectively. Quantification of HIV-1 RNA in 108 DBS mailed from remote areas with different climates demonstrated significant correlation with those obtained in plasma (r=0.95; p <0.001). CONCLUSIONS: DBS is a simple and reliable method to measure HIV-1 RNA concentration, especially when samples are mailed from remote areas to a reference center. This collection method is an economic and suitable alternative for use in developing countries.

Adolescent↗

PubMed2005

Effect of gamma irradiation on the microbiological quality and antioxidant activity of fresh vegetable juice.

A fresh vegetable juice has become a new functional food available for dieting and health. However, it poses a microbiological hazard to the consumer because it is distributed and consumed without any cooking. In this study, we applied the radiation sterilization of fresh vegetable juice, and the effectiveness of gamma irradiation for inactivating Salmonella typhimurium and Escherichia coli in the carrot and kale juice was investigated. D((10)) values of S. typhimurium in the carrot and kale juice were 0.445+/-0.004 and 0.441+/-0.006 kGy, while those of E. coli were 0.301+/-0.005 and 0.299+/-0.006 kGy. The test organisms (inoculated at 10(7) cfu/ml) were eliminated by irradiation at 3 kGy. The total phenol contents of the irradiated juice during 3 days of storage at a cold chain temperature (10 degrees C) increased significantly (P<0.05), while those of the non-irradiated juice decreased (P<0.05). The antioxidant capacity of the irradiated carrot juice was higher than that of the non-irradiated control. Therefore, it was concluded that irradiation treatments of carrot and kale juice improve the microbiological safety with maintaining or even enhancing the antioxidative activity.

Antioxidants↗

PubMed2004

Rabies deaths in Pakistan: results of ineffective post-exposure treatment.

OBJECTIVES: To estimate the incidence of rabies and the effectiveness of post-exposure treatment (PET) in Pakistan. METHODS: Rabies cases admitted from July 1993 to December 1994 to a public rabies isolation hospital were analyzed. Two samples (one sample each from a separate peripheral site) of a single batch of sheep brain vaccine (SBV) were also tested for potency by the National Institute of Health (NIH) test in May 1997. RESULTS: Forty patients were admitted with a history of clinical rabies. The median age was 22 years and 55% were under 15. Thirteen (23%) victims did not receive any vaccine; the remaining 27 (67%) received SBV only, and of these, 16 (40%) received a full course of SBV. No rabies immunoglobulins (RIG) or cell culture vaccines were administered. There were frequent power blackouts and no back-up supply at the public hospital. In-house potency testing of the vaccine batch by the manufacturer was adequate, although it was not tested by the World Health Organization (WHO) recommended NIH test. Samples of SBV of the same batch collected at the peripheral sites showed no potency. Rabies incidence was estimated to range between 7.0 to 9.8 cases per million annually. CONCLUSION: A multi-sectorial approach is needed to decrease rabies incidence in Pakistan. Public and healthcare practitioner education on prompt and appropriate PET, especially the use of cost-effective cell culture intradermal regimens, is needed urgently. The NIH test should be employed for vaccine potency testing. An independent agency is needed for monitoring vaccine quality and strategies are needed for maintaining cold chain. SBV should be replaced by locally manufactured second-generation cell culture rabies vaccine. Purified equine rabies immunoglobulin (ERIG) should be manufactured locally to meet national needs. Furthermore, effective dog control strategies should be implemented to decrease the rabies reservoir.

Adolescent↗

PubMed2006

Antibiotic resistance of raw-milk-associated psychrotrophic bacteria.

The present study proposed to evaluate the breadth of antibiotic resistance among psychrotrophic bacteria spoiling raw milks in Finland. A core of 60 isolates, retrieved from farms, trucks, and silos, phenotypically characterized, were analysed with ATB PSE strips, composed of a panel of 17 beta-lactams and non-beta-lactams antibiotics, representatives of five classes. Surprisingly, 60% of the psychrotrophs harboured multiresistant traits. We observed an increase of this feature along the cold chain of raw milk transportation.

Animals↗

PubMed2006

Introducing Vi polysaccharide typhoid fever vaccine to primary school children in North Jakarta, Indonesia, via an existent school-based vaccination platform.

OBJECTIVES: To report results on coverage, safety and logistics of a large-scale, school-based Vi polysaccharide immunization campaign in North Jakarta. METHODS: Of 443 primary schools in North Jakarta, Indonesia, 18 public schools were randomly selected for this study. Exclusion criteria were fever 37.5 degrees C or higher at the time of vaccination or a known history of hypersensitivity to any vaccine. Adverse events were monitored and recorded for 1 month after immunization. Because this was a pilot programme, resource use was tracked in detail. RESULTS: During the February 2004 vaccination campaign, 4828 students were immunized (91% of the target population); another 394 students (7%) were vaccinated during mop-up programmes. Informed consent was obtained for 98% of the target population. In all, 34 adverse events were reported, corresponding to seven events per 1000 doses injected; none was serious. The manufacturer recommended cold chain was maintained throughout the programme. CONCLUSIONS: This demonstration project in two sub-districts of North Jakarta shows that a large-scale, school-based typhoid fever Vi polysaccharide vaccination campaign is logistically feasible, safe and minimally disruptive to regular school activities, when used in the context of an existing successful immunization platform. The project had high parental acceptance. Nonetheless, policy-relevant questions still need to be answered before implementing a widespread Vi polysaccharide vaccine programme in Indonesia.

Antigens, Bacterial↗

PubMed2004

Prevalence of HBsAg mutants and impact of hepatitis B infant immunisation in four Pacific Island countries.

The prevalence rate of hepatitis B virus (HBV) infection in Pacific Island countries is amongst the highest in the world. Hepatitis B immunisation has been incorporated into national programmes at various times, often with erratic supply and coverage, until a regionally co-ordinated programme, which commenced in 1995 ensured adequate supply. The effectiveness of these programmes was recently evaluated in four countries, Vanuatu and Fiji in Melanesia, Tonga in Polynesia and Kiribati in Micronesia. That evaluation established that the programmes had a substantial beneficial impact in preventing chronic hepatitis B infection [Vaccine 18 (2000) 3059]. Several studies of hepatitis B vaccination programmes in endemic countries have identified the potential significance of surface gene mutants as a cause for failure of immunisation. In the study outlined in this paper, we screened infected children and their mothers for the emergence and prevalence of these variants in specimens collected from the four country evaluation. Although the opportunity for the emergence of HBV vaccine escape mutants in these populations was high due to the presence of a considerable amount of the virus in the population and the selection pressure from vaccine use, there were no "a" determinant vaccine escape mutants found. This suggests that vaccine escape variants are not an important cause for failure to prevent HBV transmission in this setting. Other HBsAg variants were detected, but their functional significance remains to be determined. The failure to provide satisfactory protection during such immunisation programmes reflects the need for achieving and sustaining high vaccine coverage, improving the timeliness of doses as well as improving 'cold-chain' support, rather than the selection of vaccine-escape mutants of HBV.

Adult↗

PubMed2006

Measles vaccination effectiveness among children under 5 years of age in Kampala, Uganda.

Measles control remains a great challenge in Uganda. We conducted a prospective study among household contacts aged 9-59 months to assess measles vaccination effectiveness. Index cases were measles patients seen in Kampala hospitals in 1999. Measles was diagnosed in 37/43 (86%) of unvaccinated and in 33/145 (23%) of vaccinated exposed contacts, respectively. Vaccination effectiveness was 74% (95% CI; 64-81), which was lower than expected. This may indicate the need for strengthening of the cold chain and/or introduction of a second opportunity for measles vaccination, either as part of the routine immunization program or in the form of supplementary immunization activities.

Antibodies, Viral↗

PubMed2006

Advances in vaccine stability monitoring technology.

Electronic time-temperature indicator (eTTI) monitors can be programmed to exactly follow the stability characteristics of vaccines with a high degree of realism. The monitors have a visual output, enabling vaccine status to be assessed at a glance, and can also output more detailed statistical data. When packaged with vaccine vials in groups of about 10 vials per box, the eTTI can remain with a vaccine throughout most of the vaccine's lifetime. The monitors can detect essentially all cold-chain breaks, and can detect issues, such as inadvertent freezing, that are presently not detected by other vaccine stability monitors such as Vaccine Vial Monitors (VVM).

Drug Stability↗

PubMed2006

Measles vaccination of macaques by dry powder inhalation.

Measles vaccination via the aerosol route has proven effective under field conditions, using vaccine reconstituted prior to nebulization. Inhalation of a dry powder aerosol vaccine would have additional benefits, including easier logistics of administration, reduced cold chain dependence and the potential of single dose administration. We have evaluated two candidate dry powder measles vaccine formulations in macaques. Specific immune responses were demonstrated, but levels of immunity were lower than in animals vaccinated by injection or by nebulized aerosol. These studies provide proof of principle that dry powder inhalation is a possible route for measles vaccination, but suggest that either the vaccine formulation or the method of delivery need to be improved for a better immune response.

Administration, Inhalation↗

PubMed2006

Mucosal immunization using recombinant plant-based oral vaccines.

The induction of mucosal immunity is very important in conferring protection against pathogens that typically invade via mucosal surfaces. Delivery of a vaccine to a mucosal surface optimizes the induction of mucosal immunity. The apparent linked nature of the mucosal immune system allows delivery to any mucosal surface to potentially induce immunity at others. Oral administration is a very straightforward and inexpensive approach to deliver a vaccine to the mucosal lining of the gut. However, vaccines administered by this route are subject to proteolysis in the gastrointestinal tract. Thus, dose levels for protein subunit vaccines are likely to be very high and the antigen may need to be protected from proteolysis for oral delivery to be efficacious. Expression of candidate vaccine antigens in edible recombinant plant material offers an inexpensive means to deliver large doses of vaccines in encapsulated forms. Certain plant tissues can also stably store antigens for extensive periods of time at ambient temperatures, obviating the need for a cold-chain during vaccine storage and distribution, and so further limiting costs. Antigens can be expressed from transgenes stably incorporated into a host plant's nuclear or plastid genome, or from engineered plant viruses infected into plant tissues. Molecular approaches can serve to boost expression levels and target the expressed protein for appropriate post-translational modification. There is a wide range of options for processing plant tissues to allow for oral delivery of a palatable product. Alternatively, the expressed antigen can be enriched or purified prior to formulation in a tablet or capsule for oral delivery. Fusions to carrier molecules can stabilize the expressed antigen, aid in antigen enrichment or purification strategies, and facilitate delivery to effector sites in the gastrointestinal tract. Many antigens have been expressed in plants. In a few cases, vaccine candidates have entered into early phase clinical trials, and in the case of farmed animal vaccines into relevant animal trials.

Administration, Oral↗

PubMed1996

Prospects for subunit vaccines against tick-borne diseases.

Tick-borne parasites are a serious impediment to the improvement of live-stock production in the developing world. The major parasites affecting cattle include Theileria parva, T. annulata, Babesia bigemina, B. bovis, Anaplasma marginale and Cowdria ruminantium. The control of these infections is dependent on the use of acaricides to decrease transmission by the tick vectors, and immunization of susceptible animals with live vaccines. The use of acaricide is hampered by the development of resistance, and live vaccines require cold chain facilities, which are generally unreliable in developing countries. There is therefore a need for improved vaccines that can circumvent these problems. There is a subunit vaccine being developed for T. parva based on the major surface antigen of the sporozoite (p67). A similar antigen, SPAG 1, has been identified as a candidate for T. annulata. Although several candidate antigens have been identified for Babesia spp., progress towards development of a subunit vaccine based on these antigens has been hampered by polymorphism among isolates and between species, and lack of knowledge of the immune effector mechanisms responsible for protection. The search for protective antigens of A. marginale has focused on outer membrane proteins; immunization with a variety of these antigens alone or in combination, has yielded promising results. As with Babesia, further definition of immune effector mechanisms is needed to optimize immunization strategies. The work on identifying the protective antigens of C. ruminantium is in its embryonic stages; however, two antigens have been identified and are currently being evaluated. There is high expectancy for subunit vaccines for all these diseases; however there is need for further work to elucidate the immune mechanisms in order to select appropriate antigen delivery systems.

Anaplasma↗