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In a large multicenter smallpox vaccination study carried out from 1970 to 1973, it was found that 39% of children who were initially immunized by the subcutaneous route and then challenged percutaneously with a standard vaccination did not have measurable neutralizing antibody upon follow-up. Because of this finding, a percutaneous revaccination study was conducted at the St. Louis study center in 1975 and 1976. There were four study groups, which were composed on the basis of route of primary immunization (subcutaneous or percutaneous) and whether neutralizing antibody was detectable following the original percutaneous challenge immunization. Of 52 children revaccinated, all but four had accelerated reactions. There was no difference in size of lesions or day of maximum erythema among the four study groups. Only 66% of children originally vaccinated subcutaneously who did not have postchallenge neutralizing antibody had measurable neutralizing antibody following revaccination. Transformation studies with vaccinia viral antigen before and after revaccination were performed on lymphocytes from 50 children. There was no appreciable differences in responses either before or after revaccination when the four groups were compared. However, the mean stimulation ratio for the total group increased from 2.4 before revaccination to 4.6 3 weeks later. In primary subcutaneous vaccine recipients without pre-revaccination neutralizing antibody, lymphocyte transformation correlated directly with the neutralizing antibody response.

The present four-center collaborative study was undertaken in an attempt to define the best vaccine and/or vaccination procedure for use in areas of the world that are free of smallpox. The study was designed to compare the effect of different vaccinial strains, viral concentrations, and routes of administration on the morbidity and antibody response associated with primary vaccination and standard challenge revaccination. Primary vaccinations were performed on 1,585 children; 49.6% of the children were vaccinated by the percutaneous route, and 50.4% received vaccine subcutaneously. The overall age and sex distributions of percutaneous and subcutaneous vaccinees were comparable, but there were marked differences in participants among the four study centers. Vaccines in Kentucky had a greater mean age; the greatest number of Negroid children were enrolled in St. Louis, and more of them were vaccinated by the subcutaneous route; and the dropout rate was much greater in San Diego and Colorado. An analysis of comparative interlaboratory serologic procedures with the use of 20 coded duplicate samples of serum revealed good agreement in the hemagglutination-inhibition test; results of neutralization tests had greater variability of mean titers. On duplicate samples of serum from study participants there was generally good correlation between each of the four study centers and the Center for Disease Control's reference laboratory in titers of hemagglutination-inhibiting antibody. In contrast, 38% of the neutralization titers determined at the four study centers were greater than or equal to 0.67 log10 higher than the respective titers noted at the Center for Disease Control.

As part of a large study designed to develop schedules for smallpox immunization with reduced morbidity, 799 children received primary immunization with subcutaneous vaccine. Four vaccines (New York City Board of Health calf lymph, New York City chorioallantoic membrane, CV-1, and Lister) at three dosages (103, 104, 105 pockforming units) were administered. Eighty-two percent responded with hemagglutination- inhibiting antibody at one month, and only 22% with neutralizing antibody. There was no correlation between concentration of vaccine and antibody response. The CV-1 strain was slightly but significantly less likely to induce antibody than the other three vaccines. Subcutaneous vaccination was not associated with significant temperature elevation in general. However, some children developed erythema at the vaccination site or a swollen arm, and fever did tend to occur in this small group. Four children developed nonspecific vaccinia-related rashes, and one had generalized vaccinia.

Journal Article Basic Study and Laboratory Standardization Get access Abram S. Benenson, Abram S. Benenson From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar James D. Cherry, James D. Cherry From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth McIntosh, Kenneth McIntosh From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar James D. Connor, James D. Connor From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar David W. Alling, David W. Alling From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar James Nakano, James Nakano From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Ursula T. Rolfe, Ursula T. Rolfe From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar John E. Schanberger, John E. Schanberger From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Warren A. Todd, Warren A. Todd From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Fernando DeCastro, Fernando DeCastro From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar ... Show more Frances L. Horvath, Frances L. Horvath From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Aurora Bairan, Aurora Bairan From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Irving A. Phillips, Irving A. Phillips From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar George J. Galasso, George J. Galasso From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Martha J. Mattheis Martha J. Mattheis From the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; Vesicular Disease Laboratory, Center for Disease Control, Atlanta, Georgia; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 135, Issue 1, January 1977, Pages 135–144, https://doi.org/10.1093/infdis/135.1.135 Published: 01 January 1977

Journal Article Primary Percutaneous Vaccination Get access James D. Cherry, James D. Cherry From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Kenneth McIntosh, Kenneth McIntosh From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar James D. Connor, James D. Connor From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Abram S. Benenson, Abram S. Benenson From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar David W. Alling, David W. Alling From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Ursula T. Rolfe, Ursula T. Rolfe From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Warren A. Todd, Warren A. Todd From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar John E. Schanberger, John E. Schanberger From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar Martha J. Mattheis Martha J. Mattheis From the Department of Pediatrics, University of California at San Diego and Los Angeles, California; the Department of Pediatrics, University of Colorado, Denver, Colorado; the Department of Pediatrics, St. Louis University, St. Louis, Missouri; the Department of Community Medicine, University of Kentucky Medical Center, Lexington, Kentucky; and the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland Search for other works by this author on: Oxford Academic PubMed Google Scholar The Journal of Infectious Diseases, Volume 135, Issue 1, January 1977, Pages 145–154, https://doi.org/10.1093/infdis/135.1.145 Published: 01 January 1977

Log in or Register Subscribe to journalSubscribe Get new issue alertsGet alerts Enter your Email address: Wolters Kluwer Health may email you for journal alerts and information, but is committed to maintaining your privacy and will not share your personal information without your express consent. For more information, please refer to our Privacy Policy. Subscribe to eTOC Secondary Logo Journal Logo All Articles Images Videos Podcasts Blogs Advanced Search Toggle navigation Subscribe Register Login Articles & Issues Current IssuePrevious IssuesPublished Ahead-of-Print Collections Editorials of Laura Weiss Roberts, MD, MAAM Last PageCOVID-19 and Medical EducationAddressing Race and Racism in Medical EducationeBooksView All For Authors Submit a ManuscriptInformation for AuthorsLanguage Editing ServicesAuthor Permissions Journal Info About the JournalAbout the AAMCJournal MastheadSubmit a ManuscriptAdvertising InformationSubscription ServicesReprints and Back IssuesClassified AdsRights and PermissionsFor ReviewersFor MediaFor Trainees All Articles Images Videos Podcasts Blogs Advanced Search

The present study was undertaken in an attempt to find a method to reduce smallpox immunization morbidity. Following perc. vaccination CL recipients were more likely to have a vesicular reaction (VR) than CVl recipients. In perc. vaccinees with VR and in subc. vaccinees, CL recipients more frequently developed post-vaccination neutralizing (neut.) and hemagglutination-inhibiting (HI) antibodies than CVl recipients. Six months after primary vaccination, subjects were revaccinated perc. with CL vaccine. Of 105 initial perc. CL vaccinees with VR and HI antibody, 96% had neut. antibody following revaccination; in contrast, only 69% of similar initial CVl recipients had post-revaccinetion neut. antibody. Of 107 initial subc. CL vaccinees with HI antibody, only 66% had neut. antibody following revaccination; 47% of similar subc. CVl vaccinees had post-revaccination neut. antibody. If neut. antibodies are important in resistance to smallpox, the results of this study suggest that primary subc. administration of either CL or CVl or perc. administration of CVl would be unsatisfactory alternatives to standard smallpox vaccination.