Risks connected with the use of conventional and genetically engineerd vaccines

Summary

A review is given of real and potential risks connected with the use of conventional and genetically engineered live and dead vaccines. Special attention is given to live carrier vaccines expressing one or more heterologous genes of other microorganisms. Because most carrier vaccines are still in an experimental phase, there is only limited experience with the risks of carrier vaccines. There are three potential risks of live carrier vaccines which will be discussed:

1. Changes in cell, tissue, of host tropism, and virulence of the carrier through the incorporation of foreign genes.

2. Exchange of genetic information with other vaccine or wild‐type strains of the carrier organism.

3. Spread in the environment.

Only limited experimental data are available on changes in biological behaviour of microorganisms through the incorporation of foreign genes. For example, there are indications that vaccinia virus carrying the attachment protein G of respiratory syncytial virus (RSV) replicates better in lungs of mice than vaccinia virus carrying other genes of RSV. Poxviruses carry genes that probably determine their replication in different hosts. Exchange of such host tropism genes might alter their host spectrum. Recombination between herpesvirus vaccine or wildtype strains may lead to the appearance of virulent strains with of without heterologous genes. Before carrier vaccines are applied, these risks must be thoroughly evaluated case‐by‐case. Potential methods for the design of safe carrier vaccines are discussed.

This article is based on a contribution to the course ‘Introduction of Genetically Modified Organisms into the Environment: Biosafety Aspects’, 4–14 December 1991, Wageningen, the Netherlands.     

Inactivated oil emulsion vaccines from selected clones of Newcastle disease virus

Summary

The immunogenicity of oil emulsion (OE) vaccines prepared from two selected clones of a Nigerian strain of Newcastle disease virus and two commercial vaccine strains were compared. Geometric mean haemagglutination inhibition titre was lowest in OE‐Lasota, although all four vaccines gave 100% protection against clinical Newcastle disease. The use of OE vaccines is recommended for commercial use in Nigeria.     

Antigen quantification as in vitro alternative for potency testing of inactivated viral poultry vaccines

Abstract

Routine batch control of licensed inactivated viral vaccines for poultry usually includes a potency assay as a measure of vaccine efficacy. Potency assays often consist of vaccination‐challenge experiments in the target species or in laboratory animals. Instead of measuring the protection of vaccinated animals against virulent pathogens, the serological response after vaccination can be quantified for some vaccines. In vitro antigen quantification assays would be attractive alternatives for the current potency assays because the time and costs involved could be greatly reduced and animal use could be avoided. Such in vitro assays will only be acceptable when the correlation between results and efficacy or potency has been demonstrated convincingly.

The results of our studies on antigen quantification assays indicate that, in principle, quantification of viral antigens from inactivated oil‐adjuvanted vaccines is feasible and reproducible using specially developed antigen capture ELISAs in combination with specific software for statistical analysis of the ELISA data. We have developed methods to quantify the haemagglutination‐neuraminidase (HN) and fusion (F) proteins of Newcastle disease virus (NDV), the viral protein 3 (VP3) of the infectious bursal disease virus (IBDV), and the spike‐1 (S1) protein of the infectious bronchitis virus (IBV). Vaccination experiments with inactivated ND vaccines indicate that the in vitro quantified HN‐ or F‐proteins of NDV are reliable indicators of the serological response after vaccination.     

Virology: The efficacy of a new single post‐exposure treatment of rabies in mice without vaccination

Summary

Local application of rabies immune serum and isoprinosine, an immunomodulator with antiviral activity was effective in mice infected with a sylvatic rabies virus. In this way, a single medical or veterinary treatment is only required, which is particularly important for developing but also for developed countries.

The importance of using a post‐exposure potency test to monitor rabies vaccines is emphasized. The same principle could be applied to other emerging viral infections of humans (for example, human immunodeficiency virus infection) and animals, for which no effective vaccines are available at this moment.     

Vaccination: Is it Effective in Preventing Respiratory Disease or Influencing Weight Gains in Feedlot Calves?

Respiratory disease, both undifferentiated and etiologically defined, remains a major problem in feedlot cattle. Vaccination has been used in an attempt to reduce the frequency and/or severity of respiratory disease in the first few weeks after the cattle arrive at the feedlot.

The efficacy of vaccination has been studied both in controlled laboratory experiments and field trials as well as observational studies. (In this review, efficacy refers to the ability to reduce overall treatment rate and/or increase weight gains.) This review summarizes the data resulting from studies of vaccine efficacy.

In general, there is little published data to support the use of vaccines against respiratory disease under feedlot conditions. Treatment rates and weight gains usually did not differ between vaccinated and nonvaccinated groups. The use of live bovine virus diarrhea virus vaccines was associated with a significant subsequent increase in treatment rates. Criteria to be considered in future field trials are described.

     

Investigations on live vaccines against infectious bursal disease of chicks

Summary

Four live virus vaccines against Infectious Bursal Disease (IBD) were studied with regard to their safety, immune response and applicability. None of the vaccines caused clinical symptoms or had an adverse impact on bodyweight. Differences between these vaccins were observed in their effect on the Bursa/ Bodyweight Ratio and the severity of the microscopical lesions of the bursa Fabricii. The immunosuppressive effect of IBD vaccination at one day of age on the response to Newcastle disease vaccine applied was rather low.

Three of the four vaccines induced antibodies associated with protection against challenge. Vaccination of SPF rearing chickens by drinking water at an age of 15 weeks produced an antibody response (Agar Gel Precipitin Test) whereas at an age of 23, 32 and 60 weeks it did not. Chickens of all age groups responded serologically to an intramusculair vaccination.

A correlation was found between the immunological response and the effect of the vaccines on the bursa Fabricii.     

The infective and immunogenic properties of Salmonella cholerae suis in weaner pigs

Extract

Salmonella cholerae suis (Salmonella suipestifer) is the cause of an infectious disease of weaner pigs which manifests itself as either a chronic enteritis or as an acute septicaemia in which the organism rapidly invades the body tissues and fluids. Although pigs of all ages can contract the disease, experience in New Zealand has shown that young pigs from eight to twelve weeks old are more susceptible. In 1947. experiments were commenced at Wallaceville to examine the possibility of protecting young pigs by inoculation with vaccines prepared from strains of S. cholerae suis isolated in this country. The purpose of this paper is to record and discuss the results of these experiments.     

Utility of two modified-live virus canine distemper vaccines in wild-caught fishers (Martes pennanti)

Background: Canine distemper virus (CDV) infects families in the order Carnivora. As a preventive measure, vaccinations against CDV are frequently given to mustelids in captive environments.

Objectives: Our objectives were to compare the utility between two modified-live virus canine distemper vaccines (MLV CDV's), Fervac-D® (no longer manufactured) and Galaxy-D® (now manufactured by MSD Animal Health as part of a multivalent vaccine), in developing an immune response in wild-caught fishers.

Animals and methods: The Pennsylvania Fisher Reintroduction Project (PFRP) used 14 wild-caught fishers during one year of the project to evaluate the utility of vaccinations against CDV as part of any reintroduction project. Fishers were injected subcutaneously in the nape of the neck with their designated vaccine.

Results: Fervac-D® did not effectively stimulate development of a serologic antibody response, whereas Galaxy-D® had adequate seroconversion or rise of titer levels to suggest that the general use of MLV CDV may be suitable in fishers pending further studies.

Conclusion: We recommend that future studies be conducted, evaluating the use of currently produced vaccines in fishers. Future research should also focus on the length of days required between administration of primary and booster vaccines to achieve sufficient immune response.

Clinical importance: If only primary doses are required, then hard-release reintroduction projects for fishers could be recommended. If primary and booster vaccines are required then soft-release reintroduction projects should be recommended that include captive management periods, allowing for appropriate vaccination intervals needed to maximize the probability of protection against CDV.     

Protection of chicks against Salmonella infantis infection induced by strict anaerobically cultured intestinal microflora

Summary

In two experiments newly hatched broilers were orally inoculated either with intestinal microfloras cultured under different conditions or with a suspension of intestinal homogenate and challenged with high doses (3 x 10⁵ c.f.u. per chick) of Salmonella infantis organisms.

Inocula were prepared from intestinal material of mature SPF WL hens under aerobic or strictly anaerobic conditions (< 5 ppm oxygen), and protected against atmospheric oxygen during storage. A very significant reduction of the number q/Salmonella infantis bacteria in caecal content was achieved one and two weeks after challenge in those groups of chicks which were inoculated with anaerobically cultured flora or with intestinal homogenate. In order to induce protection, obligate anaerobes had to be accompanied by facultative anaerobes. Amprolium or Monensin dit not interfere with protection. Protection induced by intestinal microflora depends on anaerobiosis during preparation, culturing, storage, and application of the protective bacteria. Starvation on the first day of life appeared to have a negative effect on protection.     

Comparison of lameness outcomes in horses with acute or chronic digital lameness that underwent magnetic resonance imaging

ABSTRACT

Aims: To compare the outcome, in terms of lameness score or return to athletic function, of horses with acute vs. chronic digital lameness that underwent magnetic resonance imaging (MRI) of the distal limb and to compare the proportion of horses that received intra-articular therapy of the distal interphalangeal (DIP) joint and pattern of diagnostic analgesia in these groups.

Methods: This is a retrospective study of horses (n?=?95) with acute (≤12 weeks; n?=?46) or chronic (>12 weeks; n?=?49) digital lameness that underwent MRI of the distal limb from 2009–2016, at two equine referral centres in the USA. Criteria for inclusion in the study were that a majority of lameness localised distal to the fetlock, and that lameness assessments for ≥12 months following MRI could be obtained from the medical record or the owner could be interviewed regarding their horse's athletic function. Outcome was characterised by an improvement score where 2?=?return to work at a previous or higher level or lameness improved by one grade or more, 1?=?return to work at a lower level or lameness improved by less than one grade, and 0?=?did not return to work or lameness grade worsened. Whether horses had received intra-articular therapy of the DIP joint and the pattern of diagnostic analgesia prior to MRI was also obtained from medical records or by interviewing the owner.

Results: There was a difference (p?=?0.004) in the proportion of horses assigned to improvement scores of 0, 1 and 2 between horses with acute or chronic lameness. There was no evidence of a difference in the likelihood of having received intra-articular therapy of the DIP joint prior to MRI between horses with chronic or acute lameness (p = 0.085). Similarly, there was no evidence of a difference in the pattern of diagnostic analgesia prior to MRI between the two groups (p = 0.94). Eighty-two percent of owners of horses with acute and 62% of those with horses with chronic lameness had a positive opinion of the utility of MRI as a diagnostic modality.

Conclusion: In a population of horses with digital lameness undergoing MRI, a difference in the outcome, in terms of lameness score or return to athletic function was identified between horses with acute lameness compared to those with chronic lameness.

Clinical relevance: Horses with digital lameness that undergo MRI when the lameness is acute may have an improved prognosis due to accurate diagnosis and earlier application of appropriate therapy.     

Standardisation of microbiological methods

Summary

The results of studies carried out under the leadership of Prof Kampelmacher to elaborate a reliable Salmonella isolation method are highlighted.

The strategy which was successfully followed is summarised in a table. This strategy can also be applied in attempts at standardisation of other microbiological methods.     

Three groups of Babesia canis distinguished and a proposal for nomenclature

Summary

Two stocks of large Babesiae from dogs originating in France, transmitted by Dermacentor reticulatus, two from North Africa, having Rhipicephalus sanguineus as vector, and one from South Africa, transmitted by Haemaphysalis leachi, were compared in cross‐immunity tests in dogs and in the indirect fluorescent antibody test (IFAT).

The French and North African stocks did not immunise against the South African one, while the North African stocks did not protect against a French one. The South African stock partially protected against a French one.

The three groups could be clearly distinguished in the IFAT These differences have practical implications for existing and future vaccines against canine babesiosis and for the serological diagnosis of atypical and chronic cases.

It is proposed to use a trinomial system of nomenclature for these groups: Babesia canis canis (Piana and Galli‐Valerio, 1895), Babesia canis vogeli Reichenow, 1937, and Babesia canis rossi (Nuttall, 1910), having Dermacentor, Rhipicephalus and Haemaphysalis ticks as their vectors respectively.     

Influence of Temperature on the Efficacy of Homologous and Heterologous DNA Vaccines against Viral Hemorrhagic Septicemia in Pacific Herring

Abstract

Homologous and heterologous (genogroup Ia) DNA vaccines against viral hemorrhagic septicemia virus (genogroup IVa) conferred partial protection in Pacific Herring Clupea pallasii. Early protection at 2 weeks postvaccination (PV) was low and occurred only at an elevated temperature (12.6°C, 189 degree days), where the relative percent survival following viral exposure was similar for the two vaccines (IVa and Ia) and higher than that of negative controls at the same temperature. Late protection at 10 weeks PV was induced by both vaccines but was higher with the homologous vaccine at both 9.0°C and 12.6°C. Virus neutralization titers were detected among 55% of all vaccinated fish at 10 weeks PV. The results suggest that the immune response profile triggered by DNA vaccination of herring was similar to that reported for Rainbow Trout Oncorhynchus mykiss by Lorenzen and LaPatra in 2005, who found interferon responses in the early days PV and the transition to adaptive response later. However, the protective effect was far less prominent in herring, possibly reflecting different physiologies or adaptations of the two fish species.

Received August 1, 2016; accepted March 10, 2017 Published online July 11, 2017     

Viral respiratory diseases (ILT,aMPV infections,IB): are they ever under control?

Abstract1.?The use of vaccines is the main approach to control of the economically important poultry viral respiratory diseases infectious laryngotracheitis (ILT), avian metapneumovirus (aMPV) infections and infectious bronchitis (IB). This paper appraises the current methods of vaccine control in the light of the nature of each virus and epidemiological factors associated with each disease.

2.?Infectious laryngotracheitis virus (ILTV) exists as a single type with a wide range of disease severity. It is a serious disease in certain regions of the world. Recent work has distinguished molecular differences between vaccine and field strains and vaccine virus can be a cause of disease. Vaccines have remained unaltered for many years but new ones are being developed to counter vaccine side effects and reversion and reactivation of latent virus.

3.?Avian metapneumoviruses, the cause of turkey rhinotracheitis and respiratory disease in chickens exists as 4 subtypes, A, B, C and D. A and B are widespread and vaccines work well provided that accurate doses are given. Newer vaccine developments are designed to eliminate reversion and possibly counter the appearance of newer field strains which may break through established vaccine coverage.

4.?IB presents the biggest problem of the three. Being an unstable RNA virus, part of the viral genome that codes for the S1 spike gene can undergo mutation and recombination so that important antigenic variants can appear irregularly which may evade existing vaccine protection. While conventional vaccines work well against homologous types, new strategies are needed to counter this instability. Molecular approaches involving tailoring viruses to suit field challenges are in progress. However, the simple use of two genetically different vaccines to protect against a wide range of heterologous types is now a widespread practice that is very effective.

5.?None of the three diseases described can claim to be satisfactorily controlled and it remains to be seen whether the newer generations of vaccines will be more efficacious and cost effective. The importance of constant surveillance is emphasised and the testing of novel vaccines cannot be achieved without the use of vaccine-challenge experiments in poultry.     

Health screening for a translocation of captive-reared tuatara (Sphenodon punctatus) to an island refuge

AIMS: To screen tuatara undergoing translocation from a captive crèche to an island refuge for evidence of health and known diseases, and apply basic epidemiological techniques to assess the significance of disease test results.

METHODS: Tuatara (n=353) were physically examined and samples were taken from a random selection (n=30) for estimated white cell counts, screening for haemoparasites, and culture for Salmonella, Yersinia, Aeromonas and Campylobacter spp. Direct faecal smears were carried out on-site, and faecal floats were later performed to assess levels of endoparasitism with helminths and protozoa (n=69). Modified Ziehl-Neelsen staining was used to screen faecal smears, and positive specimens were further screened using an immunofluorescence antibody (IFA) test for Cryptosporidium oocysts.

RESULTS: There was no evidence of external parasites on any of the animals examined and only one animal had a gross abnormality. All estimated white cell counts were in the range 2.8– 17.5 × 10⁹/L. No haemoparasites were observed. There were no enteric pathogens cultured, indicating the intestinal carriage of these bacteria in the tuatara was 9.4%. Of the 69 individual faecal samples examined, 12 (17%) had unidentified coccidial oocysts, 21 (30%) had nematode ova of various kinds, and 12 (17%) had intestinal carriage of motile protozoa consistent with Trichomonas spp and another unidentified organism. Nineteen (28%) tuatara had acid-fast oocysts present; however, IFA staining failed to detect any Cryptosporidium oocysts.

CONCLUSIONS: Our understanding of the diversity of gastrointestinal endoparasites affecting tuatara is inadequate as many of the parasite ova seen could not be identified. This is the first record of tuatara as a host for Trichomonas spp of protozoa in the gastrointestinal tract.     

Effects of using retention-pond water for dust abatement on performance of feedlot steers and carriage of Escherichia coli O157 and Salmonella spp

OBJECTIVE: To evaluate the effects of using retention-pond water for dust abatement on performance of feedlot steers and carriage of Escherichia coli O157 and Salmonella spp. DESIGN: Matched cohort studies. ANIMALS: 2 groups of feedlot steers comprising 3,510 (pathogen carriage) and 3,737 (performance) animals housed in a large commercial feedlot in the Texas Panhandle. PROCEDURE: Steers were systematically allocated to treatment pens approximately 60 days after arrival (pathogen carriage) or at arrival (performance). For evaluation of pathogen carriage, feces and hide swab specimens were collected from 25 animals in each pen within 10 days of slaughter. Samples were submitted for bacterial culture for E. coli O157 and were tested with a polymerase chain reaction-based assay for Salmonella spp. For evaluation of performance, pen weights of animals were obtained at arrival and slaughter and feed delivered to each pen was recorded. The exposure of interest for both studies was application of retention-pond water through fixed high-pressure sprinklers. RESULTS: Carriage of E. coli O157 and Salmonella spp and animal performance were not adversely affected by exposure to retention-pond water. Prevalences of E. coli O157 in feces, on hides, and either in feces or on hides for those exposed to retention-pond water were 8.3%, 8.9%, and 15.4%, respectively; prevalences for those unexposed to retention-pond water were 11.4%, 15.4%, and 22.6%, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of retention-pond water for dust abatement in feedlot pens does not adversely affect pathogen carriage or animal performance.     

Assessment of various treatments to reduce carriage of Salmonella in swine.

In this study, different strategies to reduce carriage of Salmonella spp. in pigs were evaluated. Probiotics, prebiotics, vaccination, and acidification of drinking water were assessed as means of reducing Salmonella. Acidification of water, use of egg yolk-specific immunoglobulins, and vaccination with an endotoxin vaccine did not reduce Salmonella excretion in experimentally infected pigs. A reduction of Salmonella in the colonization of mesenteric lymph nodes was observed with the use of bambermycins and a live attenuated vaccine. A reduction in the shedding of S. Typhimurium was also observed after supplementation with fructooligosaccharides in drinking water. The use of probiotics and prebiotics appeared to change the pig fecal bacterial flora as indicated by Gram staining of smears from rectal swabs.     

Experiments with a homologous,inactivated canine parvovirus vaccine in vaccination programmes for dogs

Summary

The significance of canine parvovirus (CPV) infections as a permanent threat to susceptible dogs, in particular pups, made the authors develop three liquid homologous inactivated adjuvant CPV vaccines that were compatible with existing canine vaccines and could he incorporated in current vaccination programmes. One vaccine (Kavak Parvo) contained only the CPV component, the second product (Kavak i‐LP) also contained two inactivated leptospiral antigens, and the third vaccine (Kavak i‐HLP) contained in addition an inactivated canine hepatitis virus.

This paper reports on the studies conducted to test the safety and efficacy of the three products. They were used as such and as diluents for freeze dried vaccines containing live attenuated measles, distemper, and hepatitis viruses. The study was performed in a breeding kennel where all dogs were free from CPV antibodies and the nonvaccinated sentinels remained so for the course of the study. All vaccines proved to be safe in dogs of all ages, including pregnant bitches. The efficacy of the CPV component was studied both by monitoring antibody titres for more than a year and by challenge exposure of some dogs to virulent CPV. The results obtained from these studies prove that the CPV component used in the three vaccines can be incorporated as indicated in the recommended canine vaccination programmes. The observations that both the inactivated CPV and hepatitis components do induce an active immunity in pups that are still protected by low levels of maternally derived antibodies against these viruses, make those vaccines very suitable in breeding kennels. Additional studies on a comparative basis are being continued in endemically CPV infected breeding kennels to quantify the significance of these observations in these special conditions.     

Effect of acidified feed on the prevalence of Salmonella in market-age pigs

Two trials were carried out to determine the effect of feed acidification upon Salmonella carriage in market-age pigs. In the first trial, the administration for the last 14 weeks of the fattening period of a commercial pelleted feed added with 0.6% lactic acid plus 0.6% formic acid (Lac-Formic-1.2) was compared to an unacidified standard diet (STD). A second experiment was carried out in two herds of growing pigs (Herd I, 3000 pigs; Herd II, 900 pigs) in which three different diets were assayed during the last 8-9 weeks of the fattening period: a diet containing 0.8% formic acid (Formic-0.8), a diet containing 0.4% lactic acid plus 0.4% formic acid (Lac-Formic-0.8) and a STD. In the first experiment, serological evolution of the infection was examined by ELISA and microbiological cultures (rectal samples and mesenteric lymph nodes) were also done. Feed intake by pen and the individual weight of the animals were also measured. In the second trial, blood, rectal samples and mesenteric lymph nodes were collected at slaughter in both herds (30 pigs per experimental group). In the first experiment, the acidified diet (Lac-Formic-1.2) reduced Salmonella carriers in mesenteric lymph nodes (Fisher's exact P < 0.01). In the second trial, Lac-Formic-0.8 diet significantly reduced Salmonella seroprevalence compared to the STD (P = 0.001) in both herds. Also Lac-Formic-0.8 and Formic-0.8 diets in Herd II showed a lower faecal excretion and Salmonella carriage in mesenteric lymph nodes than the STD (P < 0.05). Our results suggest that the administration of a combination of lactic and formic acids at the levels used in this study could be used to reduce Salmonella prevalence in finishing pigs.     

Congress report on progress in pestivirus virology

Summary

This mini‐review highlights new information on various research aspects presented by specialists from all over the world at the 4th Pestivirus meeting held in Giessen (Germany) from March 15–19, 1999. Especial attention is paid towards differences in humeral and cellular immune response of naive and persistently infected calves with BVDV, and towards BVD eradication programmes m the Scandinavian countries.

The development of techniques for an early diagnosis of CSF in live pigs and the progress on both sub‐unit and MLV marker vaccines against this disease are reported.