Vaccinia Viruses as Vectors for Vaccine Antigens Vaccinia Viruses as Vectors for Vaccine Antigens Proceedings of the Workshop on Vaccinia Viruses as Vectors for Vaccine Antigens, held November 13-14, 1984, in Chevy Chase, Maryland, U. S.A. Editor: GeraldV.Quinnan,Jr.,M.D. Director, Division of Virology Center for Drugs and Biologics Food and Drug Administration Bethesda, Maryland Elsevier New York • Amsterdam. Oxford .... i © 1985 by Elsevier Science Publishing Co., Inc. All rights reserved. This book has been registered with the Copyright Clearance Center, Inc. For further information, please contact the Copyright Clearance Center, Salem, Massachusetts. Published by: Elsevier Science Publishing Co., Inc. 52 Vanderbilt Avenue, New York, New York 10017 Sole distributors outside the United States and Canada: Elsevier Science Publishers B.V. P.O. Box 211, 1000 AE Amsterdam, the Netherlands Library of Congress Cataloging in Publication Data Workshop in Vaccinia Viruses as Vectors for Vaccine Antigens (1984: Chevy Chase, Md.) Vaccinia viruses as vectors for vaccine antigens. Includes index. I. Vaccines--Congresses. 2. Vaccinia--Congresses. 3. Viralantigens-- Congresses. 4. Smallpox--Congresses. I. Quinnan, Gerald V. 1I. Title. [DNLM: 1. Antigens, Viral--immunology--Congresses. 2. VacciniaVirus-- genetics--congresses. 3. VacciniaVirus--immunology--congresses. 4. Viral Vaccines--immunology--congresses. QW 165.5.P6 W926v 1984] QR189.W674 1984 615'.372 85-12960 ISBN 0-444-00984-1 Manufactured in the United States of America CONTENTS Preface ..... ..... ° . ............... ix Participants .............................. xi Part I: BIOLOGY OF VACCINIA AND OTHER ORTHOPOX VIRUSES I Chairpersons: G. Schild and J. Nakano Vaccinia Virus ...................... 3 D. Baxby Aspects of the Biology of Orthopox Viruses Relevant to the Use of Recombinant Vaccines as Field Vaccines ...... 9 K.R. Dumbell Molecular Biology of Vaccinia Virus: Structure of Pox Virus DNA ................ 15 W.K. Joklik Molecular Biology of Vaccinia Virus: Strategies for Cloning and Expression of Foreign Genes ......... 27 B. Moss Genetic Basis for Vaccinia Virus Virulence ........ 37 R.M.L. Bullet and B. Moss Part II: SMALLPOX VACCINES 47 Chairperson: G.V. Quinnan, Jr. Complications of Smallpox Vaccination .......... 49 I. Arita and F. Fenner _ Utilization of Vaccine in the Global Eradication of Smallpox ......................... 61 D.A. H_nderson and I. Arita \ _ Vaccinia Virus Vaccines: Virulence and Attenuation of Vaccinia Strain Variation ................ 69 _i J.M. Neff A Comparative Study of Four Smallpox Vaccines in Children ......................... 77 K. McIntosh Low Neurovirulent Variant of Lister Strain of Vaccinia Virus ...................... 85 S. Kato Properties of Attenuated Mutant of Vaccinia Virus, LC16m8, Derived from Lister Strain ............ 87 S. Hashlzume, R. Yoshizawa, M. Morita and K. Suzuki Immunogenicity of Vaccinia Viruses: Responses to Vaccination ................. 101 J.D. Millar Smallpox Vaccine In Vivo Production and Testlng ..... 109 D.P. Metzgar vl Tissue Culture Smallpox Vaccine ............ 113 A.C. Hekker Capability of Developing Countries to Produce Vaccinia Vector Vaccine ..................... 117 I. Arita Part III: EXPERIMENTAL RECOMBINANT VACCINIA VIRUS VACCINES 127 Chairpersons: R. Chanock and W. Dowdle Vaccinia Virus Recombinants as Live Vaccines Against Hepatitis B Virus and Malaria ............. 129 G.L. Smith and B. Moss Vaccinia Vectored Vaccines ............... 137 E. Paoletti, M.E. Perkus, A. Piccini, S. Wos, and B.R. Lipinskas Infectious Vaccinia Virus Recombinants Express Herpes Simplex Virus Glycoprotein D and Protect Against Lethal and Latent Infections of HSV .......... 153 K. Cremer, C. wohlenberg, M. Mackett, B. Mos% and A.L. Notkins Induction of Virus Neutralizing Antibodies and Protection Against Rabies Using a Vaccinia Rabies Glycoprotein Recombinant ................ 163 B. Dietzschold, T.J. Wiktor, and H. Koprowski Influenza Virus Specific Cell-Mediated Immunity to Vaccinia Virus Recombinants .............. 169 J.R. Bennink, J.W. Yewdell, G.L. Smith, and B. Moss Intranasal Vaccination with Recombinant Vaccinia Containing Influenza Hemagglutinin Prevents Both Influenza Virus Pneumonia and Nasal Infection: Intradermal Vaccination Prevents only Viral Pneumonia ....................... 175 P.A. Small, Jr., G.L. Smith, and B. Moss Infectious Vaccinia Virus Recombinants that Express the Epstein-Barr Virus Membrane Antigen gp340 ..... 179 M. Mackett and J.R. Arrand Vaccinia Virus Recombinants Expressing Vesicular Stomatitis Genes Immunize Mice and Cattle ....... 187 T. Yilma, M. Mackett, J.K. Rose, and B. Moss Infectious Vaccinia Virus Recombinant that Expresses the Surface Antigen of Porcine Transmissible Gastroenteritis Virus (TGEV) .............. 201 S. Hu, J. Bruszewski, and R. Smalling Part IV: OTHER VIRUSES AS VECTORS FOR VACCINE ANTIGENS 209 Chairpersons: R. Chanock and W. Dowdle Genetic Engineering of Herpes Simplex Virus Genomes for Attenuation and Expression of Foreign Genes .... 211 B. Roizman and M. Arsenakis vii Part V: CONSIDERATIONS OF THE SAFETY, EFFICACY AND POTENTIAL APPLICATIONS OF RECOMBINANT VACCINIA VIRUSES 225 Chairperson: G. Noble Potential Applications of Vacclnla Virus Vectors for Immunoprophylaxls ................... 227 F. Brown Considerations of Safety, Efficacy and Potential Applications of Vacclnla Vectors for Immunoprophylaxls: An Alternative Approach for Control of Human Diseases For Which Vaccines are Available ........... 231 D.T. Karzon Considerations of Safety, Efficacy, and Potential Application of Vacclnla Vectored Vaccines for Immunoprophylaxls Against Animal Diseases ....... 237 F.A. Murphy Panel Discussion: Needs for Further Laboratory and Clinical Research, Safety and Ethical Considerations. 241 F. Dienhardt, K. Warren, W. Jordan, and G.V. Qulnnan, Jr. Index ......................... 253 ix PREFACE The use of viruses as vectors for expression of heterologous antigens in mammalian cells in vivo exemplifies an exciting recent advance in the application of recombinant DNA technology for vaccine production. In many respects vaccinia virus is highly suited for this purpose. Vaccinia virus vaccines were used extensively world-wide during the smallpox eradication campaign, and were generally very well tolerated, highly i mmunogenic, easily manufactured and readily applied in mass vaccination efforts. Even with its outstanding performance record, however, the possibility of reintroduc- ing the use of this virus on a wide scale in man or animals raises many public health and ethical concerns. Although very rarely, serious or fatal complications of vaccinia virus infections did occur, and they occurred in contacts of vaccinees as well as in vaccinees themselves. The potential occurrence and significance of similar complications must be evaluated in considering approaches to devel¢_ment of recombinant vaccinia virus vaccines. Even if there were no known risks, the reintroduction of the virus into populations that are not: exposed currently should be done only after careful consideration of the benefits to be achieved. Other major questions that must be addressed at: the outset include: What strain(s) of vaccinia virus should be used? How should vaccines be manufactured? What tests should be done to assure acceptability of vaccines for use in field trials? What biologic propezties of vaccine strains should be evaluated? In whom should vaccine trials be performed? This book represents the proceedings of a Workshop on Vaccinia Viruses as Vectors for Vaccine Antigens, cosponsored by the United States Public Health Service, the World Health Organization, and the National Institute for Biologic Standards and Control, London, held November 13 and 14, 1984, in Chevy Chase, Maryland. The purpose of the Workshop was to begin devel- oping answers to the questions indicated above. The data presented and relevant to these questions emanate both from studies performed during the smallpox eradication campaign and from exciting recent laboratory work on molecular biology, expression of foreign genes, determinants of virulence, and immunology of vaccinia virus infections. It is evident from these data that there are unlikely to be any insurmountable objections to the use of recombinant vaccinia virus vaccines, and that they offer great promise for use as safe and effective immunogens. Work on developing can- didate strains for human administration will hopefully progress rapidly. The use of vectors other than vaccinia virus may also prove feasible. This Workshop was followed by a meeting of consultants to the World Health Organization with the purpose of advising on evidence relevant to the public health, ethical and scientific concerns about these recombinant vaccines, and formulating draft requirements for the use of recombinant vaccinia virus vaccines. These draft requirements will be under continued development for many months. However, the intent of the World Health Organization to publish them should be viewed as an indication of the enthusiasm with which this approach has been greeted. The list cf human and veterinary diseases against which vaccines of this type might be used is long and the death and suffering that might be prevented are great. The process of developing any vaccine is an arduous one, and it is never certain at the outset that any specific approach will result in a safe and effective product. It is clear that the long history of vaccinia virus is far from over and there are many