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Rabies Postexposure Prophylaxis with Human Diploid Cell Rabies Vaccine: Lower Neutralizing Antibody Titers with Wyeth Vaccine

MMWR 34(7);90-2

Publication date: 02/22/1985

Table of Contents


Editorial Note




On February 16, 1985, Wyeth Laboratories recalled Wyeth human diploid cell rabies vaccine (WYVACTM) from the market. This resulted from two postlicensure studies of antibody responses after postexposure prophylaxis with human diploid cell rabies vaccine (HDCV) conducted by CDC over the last 6 months. The studies--one, a passive surveillance system, and the other, a randomized prospective study--demonstrated that not all individuals receiving postexposure prophylaxis with Wyeth Laboratories' HDCV had antibody titers acceptable by the CDC criterion* and that antibody titers after rabies postexposure prophylaxis with Wyeth HDCV were lower than those with Merieux HDCV (IMOVAXTM).

In the passive surveillance system, sera were examined from 39 persons (in four states) who had completed postexposure prophylaxis with rabies immune globulin (RIG) and five doses of HDCV; 22 had been vaccinated with Merieux vaccine, and 17, with Wyeth vaccine. Two of the 17 Wyeth vaccine recipients had an inadequate titer by the CDC criterion (1,2); one had no detectable titer. Three additional persons had low titers (acceptable by CDC's criterion but not by the World Health Organization's criterion). In contrast, all 22 recipients of Merieux vaccine had adequate titers by both criteria.

The reason for some low responses after postexposure administration of Wyeth HDCV is unknown. The product has consistently met all applicable release standards, and the failures could not be attributed to a single vaccine lot. Certain host factors may have contributed to the poor response. The median age of the five poor responders to Wyeth vaccine was 42 years, compared with 21 years for the responders. One low responder was a 42-year-old person with epilepsy on chronic phenytoin therapy; phenytoin has inhibitory effects on some immune functions (3). The individual who showed no detectable neutralizing antibody after prophylaxis with Wyeth vaccine was a healthy but obese (6 ft., 275 lbs.) 32-year-old male who received all injections in the buttocks. Two of the three low responders also received their vaccine in the buttocks.

While the surveillance program was being conducted, a prospective study was undertaken. The study participants received rabies postexposure prophylaxis of RIG with five doses of either Merieux or Wyeth vaccine of similar potencies. Titers in the Merieux group were significantly higher (Table 1), although all persons in both groups had acceptable titers 2-4 weeks after completing prophylaxis (4). Reported by C Langkop, R Martin, DVM, Illinois Dept of Public Health; M Catalano, MD, Montefiore Hospital and Medical Center, New York City, A Porter, Southampton, C Trimarchi, New York State Dept of Health; J Jarvis, Emory University School of Medicine, Atlanta, E Weir, T McKinley, RK Sikes, DVM, State Epidemiologist, Georgia Dept of Human Resources; D Zeidner, MD, A Bowman, J Dennehy, MD, C Rudy, G Stover, R Leipold, MD, T Royer, MD, M Ryan, MD, G Stover, S Toor, MD, T Martin, MD, Geisinger Medical Center, Danville, J Maksimak, MD, RH Kaiser, MD, G Lattimer, MD, M Hart, C Sinner, Divine Providence Hospital, Williamsport, B Jones, DVM, E Witte, VMD, C Hays, MD, State Epidemiologist, Pennsylvania State Dept of Health; Office of Biologics, Research, and Review, Center for Drugs and Biologics, US Food and Drug Administration; Div of Viral Diseases, Center for Infectious Diseases, Div of Field Svcs, Epidemiology Program Office, CDC.

Editorial Note

Editorial Note: Annually, approximately 20,000 people receive rabies postexposure prophylaxis with HDCV in the United States (5). Since the early 1980s, when duck embryo vaccine was replaced by the more immunogenic HDCV, no person has developed rabies after having received the recommended postexposure prophylaxis of RIG and vaccine. Until the current report, data showed that Wyeth HDCV administered intramuscularly induced acceptable antibody levels.

The present low responses in some individuals may be due to both intrinsic differences in the two vaccines and accompanying host factors. Wyeth HDCV is a subunit vaccine, disrupted with tri-(n)butyl phosphate and further inactivated with beta-propiolactone, while Merieux HDCV is a whole virus vaccine inactivated with beta-propiolactone. Other factors, including older age, receipt of mildly immunosuppressive medications and administration of the vaccine into the buttocks, may also have contributed to the lower responses. Injections in the gluteal region will almost always be delivered into fat (6). It is not known whether there is a difference in absorption of the two types of HDCV when administered by this route. It has recently been recognized that administration of hepatitis B vaccine in the gluteal area probably results in a poorer response than vaccination in the deltoid (7). It is recommended that all adult immunizations be administered in the deltoid region (8,9); the deltoid area is the preferred site for HDCV vaccination. The gluteal area remains an acceptable site for large volumes of RIG. HDCV and RIG should never be administered in the same anatomic sites.

One 1.0-ml intramuscular booster with Merieux HDCV in the deltoid area is recommended, based on review of available information, for all persons who have been potentially exposed to rabies since October 15, 1984, and who have received postexposure prophylaxis with Wyeth HDCV (unless sera obtained after postexposure prophylaxis demonstrated an acceptable antibody titer). Merieux HDCV can be obtained by calling 800-327-2842. Anyone currently receiving Wyeth vaccine should complete the course with Merieux vaccine and does not require an additional booster. Serologic testing is recommended if a systemic allergic reaction (serum sickness or urticaria) occurred during previous administration of postexposure prophylaxis. In that case, an acceptable serologic response obviates the need for a booster vaccine dose. Serum testing continues to be indicated if a patient who received postexposure prophylaxis with HDCV is immunosuppressed (by diseases or medications) (1). State health departments can be contacted for the addresses of laboratories where serologic testing is available.

Wyeth vaccine administered preexposure and in the recommended 1.0 ml intramuscular doses (three injections) has been effective in inducing antibodies. Based on currently available information, persons so vaccinated need neither serologic testing nor booster doses of HDCV, except for those select groups previously identified (1). In the event of future exposure to rabies, persons who have received preexposure prophylaxis with either type of HDCV should receive two 1.0-ml intramuscular booster doses of HDCV (one each on days 0 and 3), as is currently recommended (1).

*At present, CDC considers a neutralizing antibody titer that produces complete inhibition in the rapid fluorescent focus inhibition test at 1:5 dilution or greater (1:11 or greater by the Reed-Muench method) an acceptable response to immunization (1). The World Health Organization considers 0.5 IU/ml or greater (2) an acceptable response (approximately equivalent to 1:56 by the Reed-Muench method or complete inhibition at the 1:25 dilution).


  1. ACIP. Rabies prevention--United States, 1984. MMWR 1984;33:393-402, 407-8.
  2. WHO Expert Committee on Rabies. Seventh Report. World Health Organization Technical Report Series 709, 1984:28.
  3. Grob PJ, Herold GE. Immunological abnormalities and hydantoins. Brit Med J 1972;2:561-3.
  4. CDC. Unpublished data.

  5. Helmick CG. The epidemiology of human rabies postexposure prophylaxis, 1980-1981. JAMA 1983; 250:1990-6.
  6. Cockshott WP, Thompson GT, Howlett LJ, Seeley ET. Intramuscular or intralipomatous injections? N Engl J Med 1982;307:356-8.
  7. CDC. Unpublished data.

  8. ACIP. General recommendations on immunization. MMWR 1983;32:1-8, 13-7.
  9. Committee on Immunization, Council of Medical Societies, American College of Physicians. Guide for adult immunizations. 1985:1.


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