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Accidental infection of laboratory worker with recombinant vaccinia virus SIR,--Cooney et all report the effects of vaccination of healthy volunteers with recombinant vaccinia virus (rVV) expressing the gpl60 envelope protein of HIV. Those previously vaccinated against smallpox showed transient HIV-specific T-cell responses, but no specific antibody response. By contrast, vaccinia-naive volunteers showed good T-cell and serological responses to the HIV envelope protein. We now report the effects of accidental infection with rVVs expressing two individual proteins from respiratory syncytial virus (RSV). A technician was manipulating five rVVs expressing individual proteins from RSV late on a Friday afternoon during September, 1990. The recombinants were based on the WR strain of vaccinia with RSV genes inserted into the vaccinia TK gene under the 7.5K promoter (generously provided by Prof G. Wertz, Dr A. Ball, and Dr K. Anderson, University of Alabama, Birmingham, USA). Fine needles held in the right hand were being used to transfer live virus to materials held in the left hand. While the technician was transferring an rVV expressing the major surface glycoprotein G of RSV, the needle slipped and passed through the glove into the left thumb. The technician continued work with another rVV expressing the 22 K (second matrix) protein of RSV, again slipped and inoculated the forefinger of the left hand. In both cases, the needle caused slight pain but no bleeding. The technician had previously used the same method of manipulation for 13 months without incident; this procedure has now been modified to prevent similar accidents occurring. The technician had been vaccinated in the left upper deltoid region by scarification with standard smallpox vaccine (Public Health Reference Laboratory, originally of Swiss Serum Institute strain) in July, 1989. That primary infection had produced a strong reaction with local swelling, an erythematous papular rash across the trunk, severe regional lymphadenopathy (preventing movement of the shoulder), and systemic symptoms necessitating time off work. This illness resolved without specific intervention. After the accidental inoculation, no symptoms occurred for 3 days. The sites of inoculation then became itchy and by day 4 they were red and papular. By days 5 and 6 the lesions were discharging serous fluid and reached a maximum diameter of about 1 cm. There were no systemic effects and there was very little local swelling. The lesions were kept under occlusive dressings and healed spontaneously. No information is available about the technician’s immune status with regard to RSV before the accident. After the inoculation, serum was repeatedly tested in our laboratory for RSV-specific IgG, IgM, IgA, and IgE. No ELISA-binding antibody response occurred. The peripheral blood lymphocytes were kindly tested by Dr G. L. Toms, Dr R. Scott, Dr K. Nash, and Dr J. J. Anderson (Division of Virology, University of Newcastle upon Tyne, UK) for proliferation in response to purified RSV proteins. Good responses were seen to the F and 22 K proteins, but responses to the 34 K and major surface glycoprotein G were poor. Such a pattern is not unique in normal laboratory volunteers.2 In our own laboratory, the technician’s lymphocytes were stimulated with dendritic cells infected with RSV and the responding cells tested for cytotoxic recognition of Epstein-Barr virus-transformed B cells infected with a panel of nine rVV, expressing individual RSV proteins. Strong recognition of the 22 K protein was demonstrated, a result which we have not seen in normal donors but which has been observed in donors recently exposed to RSV (unpublished). Our findings are consistent with those of Cooney et al, in that our previously vaccinated technician developed no serological response to RSV virus, but did show some evidence of T-cell recognition of the 22 K protein. Diseases that might potentially be prevented by vaccination with rVV include influenza A, rabies, malaria, and herpes simplex, besides infantile bronchiolitis (RSV infection)3 and AIDS. If previously vaccinated individuals respond poorly to recombinant proteins expressed by subsequent rVV, it is important that vaccinia virus should be administered only to individuals with a high probability of benefits. These rVVs are potentially dangerous for three reasons. The WR strain was originally selected by serial passage in mouse brain and is

potentially neurotropic. Virulence in mice is much reduced by disruption of the TK with a transgene, but the pathogenicity of such modified viruses has not been tested in man. Secondly, it is possible that the transgene product could become incorporated into the vaccinia virus coat, conferring the transmissibility or other properties of the donor virus to the rVV. Fortunately, this has not been described and we have not seen enhanced pathogenicity of rVV expressing RSV coat proteins when used for infection by the respiratory route in rodents (unpublished). Thirdly, the rVVs that infected the technician can confer some resistance to infection with RSV in animal models, but can greatly increase the severity of subsequent bronchiolitis (unpublished). The technician did not become infected with RSV during the winter of 1990-91, but will continue to be observed during subsequent RSV seasons. The accident described reinforces our belief (and that of others4-6) that selected laboratory personnel should be vaccinated, although this policy has been challenged.7 Had the accidental inoculation been a primary infection, the local effects in the hand would probably have been severe. Although secondary inoculation does produce small local lesions, our hope is that vaccination will help to prevent dissemination of rVV if accidents do occur.

Department of Medicine, St Mary’s Hospital Medical School, London W2 1PG, UK 1

P. J. M. OPENSHAW W. H. ALWAN A. H. CHERRIE F. M. RECORD

Cooney EL, Collier AC, Greenberg PD, et al Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein.

Lancet 1991; 337: 567-72. JJ, Harrop JA, Peers H, Briggs H, Toms GL, Scott R. Recognition of respiratory syncytial (RS) virus proteins by human and BALB/c CD4+ lymphocytes. J Med Virol (in press). 3 Collins PL, Purcell RH, London WT, Lawrence LA, Chanock RM, Murphy BR. Evaluation in chimpanzees of vaccinia virus recombinants that express the surface glycoproteins of human respiratory syncytial virus. Vaccine 1990; 8: 164-68. 4. Centers for Disease Control and National Institutes of Health. Biosafety in microbiological and biomedical laboratories. Washington, DC US Government 2. Anderson

Printing Office, 1988: 78-79. 5 Danner K. Smallpox vaccination for investigators Lancet 1989; ii: 1337. 6. Advisory Committee on Dangerous Pathogens and Advisory Committee on Genetic Modification. Vaccination of laboratory workers handling vaccinia and related poxviruses infectious for humans. London: HM Stationery Office, 1990 7. Wenzel RP, Nettleman MD. Smallpox vaccination for investigators using vaccinia recombinants. Lancet 1989; ii: 630

Hepatitis C virus infection

in Egyptian volunteer blood donors in Riyadh

SIR,-During routine donor screening for antibody to hepatitis C (anti-HCV) with a commercially available enzyme immunoassay (anti-C1OO ELISA, Abbott Laboratories), we found a surprisingly high proportion (20 ([19-2%] of 104) of repeatedly reactive serum samples among Eygptian volunteer blood donors attending our blood bank in Riyadh. By contrast, the seroprevalence in Saudis was only 1’3%, in Sudanese 1’9%, and in Yemenis 2-4%. Elsewhere the reported prevalence of anti-HCV among healthy blood donors is even lower: 05% in the UK,2 04% in Germany, 07% in France, 0-9% in Italy, and 1-2-14% in virus

Japan.3 We have examined in detail a panel of 32 ELISA-positive serum samples from Egyptian donors using a second generation recombinant immunoblot assay (RIBA, Ortho Diagnostic Systems), which includes one structural and three non-structural antigens. With this RIBA test, 30 sera (94%) were positive by the manufacturer’s criteria, and the remaining 2 were indeterminate. This correlation between RIBA positivity and repeatable reactivity in ELISA suggests a very high degree of C-100 ELISA specificity for this cohort of donors-far greater than that reported for Dutch or US donors in whom under half the ELISA-reactive samples were confirmed as antibody positive by RIBA (22%" and 45%,5 respectively). The high predictive value of ELISA seen among our Egyptian donors (94%) has so far been found only in groups with identifiable risk factors for HCV infection---eg, 84% of samples from previously transfused individuals6 and 96% of French patients with chronic non-A, non-B hepatitis.’ 14 of the RIBA-positive and the 2 RIBA-indeterminate samples from our panel of serum samples were tested for HCV-RNA by the

Accidental infection of laboratory worker with recombinant vaccinia virus.

459 Accidental infection of laboratory worker with recombinant vaccinia virus SIR,--Cooney et all report the effects of vaccination of healthy volunt...
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