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Abstract Background The Maedi-Visna (MV) lentivirus causes two slowly progressive eventually fatal diseases of sheep, Maedi, a progressive interstitial pneumonia, and Visna, a progressive demyelinating disease of the central nervous system. Other lentiviruses also cause fatal slow infections in their natural hosts, e.g. the HIV virus in humans. Results of experimental vaccination against any lentivirus where vaccinees are challenged by natural routes, may therefore be of general interest. From 1991–1998 experiments with formalin-inactivated whole Maedi-Visna virus vaccine were carried out in the Department of Microbiology at the University of Iceland. Western Blot tests showed good immune response to all major proteins of the virus. When aluminium hydroxide was added to the vaccine all vaccinees developed neutralizing antibodies to the vaccine strain at titers 1/8 – 1/256. After housing 5 twin pairs, one twin in each pair vaccinated, the other unvaccinated, with infected sheep for 4 years, all the unvaccinated twins became infected, but only 2 of their vaccinated siblings as confirmed by virus cultivation experiments on tissues from their lungs spleens lymph nodes and choroid plexuses. Results One twin in each of 40 female twin pairs, born into a Maedi-Visna-infected sheep flock and kept under natural farming conditions in Cyprus, was vaccinated at birth, 3 weeks and 3 months, with formalin-inactivated whole Maedi-Visna lentivirus vaccine adjuvanted with aluminium hydroxide. 17 mothers of the twins were seronegative, 13 seroconverting and 10 had old infection. Of 17 vaccinees born to seronegative mothers 9 were uninfected at 28 months, but only 2 of their unvaccinated siblings. Of 13 unvaccinated twins born to seroconverting mothers, 12 caught infection during their first 10 weeks, but only 4 of their vaccinated siblings. Vaccination had no effects on 10 vaccinees born to mothers with long-standing Maedi-Visna infections and broad andibody response at birth of their lambs. Conclusion Compared with their unvaccinated siblings, natural infection was delayed in significant number of vaccinated twins born by seronegative and seroconverting mothers and vaccinated at birth, 3 weeks and 3 months with formalin inactivated whole MV vaccine adjuvanted with aluminium hydroxide. Maternal antibodies interfered with vaccination so early in life if the mother had old infection.

Maedi-visna virus (MVV), a lentivirus of sheep, shares with other lentiviruses the ability to establish a lifelong infection. In this study five sheep were infected intravenously with MVV and housed together with a number of uninfected sheep for natural transmission. All virus isolates from ten sheep that had been infected naturally had multiple mutations in the principal neutralization domain in Env and were antigenic variants, while three of four isolates from the carrier sheep had identical sequences to the infecting strain and were not antigenic variants. There was evidence of positive selection in the gene, particularly in amino acids comprising the neutralization epitope and some adjacent glycosylation sites. Together these results suggest that virus persistence is acquired by a reservoir of latent viruses, and that there is selection for antigenic variants of virus that is transmitted naturally., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Sixteen Icelandic sheep were vaccinated against Visna-Maedi infection with formalin inactivated whole virus vaccine to which alun was added as an adjuvant. Western Blots showed that all the vaccinees responded to the major proteins of the virus. They all developed neutralizing antibodies ranging in titers from 1/8-1/256 at maximum for individual sheep. Passive transfer of antibodies and neutralizing activity from vaccinated ewes to their lambs was demonstrated. Exposure of the 16 vaccinees and their 16 unvaccinated control sheep to natural infection is attempted by housing them with heavily infected sheep. After 9 months of exposure there is no seroconversion in the unvaccinated group. Only time can tell, whether or not such conventional vaccination with inactivated vaccine protects the vaccinees.

A programme to eradicate congenital rubella from Iceland was started in 1979, based on (1) screening of all females aged 12-45 years for rubella antibodies and (2) vaccination of all seronegative persons with the RA/27/3 rubella vaccine, given free of charge. Thus, individual protection was offered to all who needed it. The collection of serum samples was planned to last for 2 years while, simultaneously, the already established rubella screening and immunization programmes for 12-year-old schoolgirls and pregnant women continued.During assessment in 1983, 95.2% of females in the first 7 age groups (by now aged 14-20 years) participating in the school programme had been tested and 80.4% of them were found to be naturally immune. Of the seronegatives, 93.7% were subsequently vaccinated, thus giving an overall immunity rate of 98.8%. Among the women in the peak of the childbearing period (by now aged 21-35 years), 84.4% had been tested and 92.7% were found to be naturally immune; vaccination of 61.4% of seronegative individuals then gave an overall immunity rate of 97.2% for this age group.If it is assumed that the natural immunity rate of females still untested is like that of the above groups, then the percentage of non-immune persons is at present 2.1% in the younger group and 3.4% in the older.

Cost-benefit analyses show that prevention of congenital rubella infection is cost-effective. Before selection of a strategy, local epidemiologic and social factors need examination. Analyzing these factors may lead to considerable cost reduction, especially if results from preexisting screening programs are available. The cost-effectiveness of different strategies are compared in Iceland. Systematic screening of women and teenage girls, with vaccination of seronegative persons, was more cost-effective than vaccination of all children. Previously unscreened females aged 12-40 years were screened and seronegative females were vaccinated for one-third the cost of vaccinating all children aged two to 12 years. Continuation of this program by vaccinating 12-year-old girls was two to three times more cost-effective than vaccination of all two-year-old children. Use of rubella vaccine in combined vaccines proved the most expensive strategy, with or without revaccination of teenagers.

Iceland, as a few other European countries, has used inactivated vaccine against poliomyelitis from the beginning in 1956. No cases of paralytic polio occurred since 1960. For 17 years neither isolations of poliovirus nor suspected cases of the clinical disease have been recorded. Studies on neutralizing antibodies in sera of vaccinees were not too encouraging after 4 injections. A 5th vaccination of IPV was therefore given to those children who lacked antibodies to any type of poliovirus. One month after the 5th injection 70% had antibodies against all 3 types of poliovirus and only 2% lacked antibodies against both types 1 and 3. In countries where no virus to boost immunity exists any longer during the life of an individual it may be necessary to secure booster effects at regular intervals after primary vaccination and later in life. This will be included in the vaccination schedule against polio in Iceland.

Sigurdsson's three criterions for a slow viral infection are quoted and discussed and the background of his work briefly described. A fourth criterion for a slow viral infection, is suggested, infection of the hosts lymphoid tissues, which is a common feature of slow infections that have been observed. The general properties of the maedi-visna virus, the diseases and the immune response it causes are discussed. Sheep and goats are susceptible to natural maedi-visna infection. In the goat an identical retrovirus causes arthritis. Arthritis has not been found in maedi-visna infected sheep. Two subacute spongiform encephalopathies of animals are shortly reviewed, scrapie in sheep and goats and transmissible mink encephalopathy (TME). General properties of the very unusual scrapie agent are mentioned briefly. The third type of a slow viral infection is mentioned, Aleutian mink disease, an immunopathological disorder of certain minks caused by a selective infection of lymphoid cells.