William H. Bancroft

Prevention of endemic HAA-positive hepatitis with gamma globulin. Use of a simple radioimmune assay to detect HAA.

Abstract A simple radioimmune assay method was used to detect Australia (HAA) antigen in serum specimens from normal military blood donors and soldiers with endemic icteric hepatitis. This method detected more than twice the number of HAA-positive specimens among both groups of subjects than by other available methods. Furthermore, it detected all positive specimens found by the agar-gel diffusion, immunoelectro-osmophoresis, complement-fixation and passive hemagglutination-inhibition methods. The radioimmune assay method showed that about 1 per cent of screened military blood donors and 25 per cent of soldiers with icteric endemic hepatitis had HAA in their serum. In these patients with hepatitis we had previously shown that the prophylactic administration of human serum gamma globulin decreased the incidence of both HAA-positive and HAA-negative endemic icteric hepatitis. The availability of a new and more sensitive assay for HAA provided more convincing evidence that injection of gamma globulin with a ...

Immunogenicity of an Inactivated Hepatitis A Vaccine

Although hepatitis A is a disease without chronic sequelae, it is associated with serious morbidity in adults. An inactivated hepatitis A vaccine prepared at the Walter Reed Army Institute of Resea...

Hepatitis A in the US Army: epidemiology and vaccine development

Control of hepatitis A has been an important concern for US military forces in war and peace. Immune serum globulin, although effective, is exceedingly cumbersome to use. The prevalence of antibody against hepatitis A is decreasing in young American soldiers, putting them at risk of hepatitis A during deployment. The US Army has been an active participant in development of hepatitis A vaccine. The first successful cell-culture-derived, formalin-inactivated hepatitis A vaccine was developed at the Walter Reed Army Institute of Research. This prototype vaccine was shown, in 1986, to be safe and immunogenic for humans. Since then we have evaluated the following issues related to the use of inactivated hepatitis A vaccines in military populations. Immunogenicity of vaccine derived from the CLF and HM175 strains; immunogenicity of hepatitis A vaccine given by jet injector; immunogenicity of hepatitis A vaccine when given with hepatitis B vaccine; immunogenicity when given in shortened schedules; safety and immunogenicity in Thai children; and efficacy under field conditions in the tropics. The hepatitis A vaccines which we tested are safe and highly immunogenic. Immunization by jet gun confers immunity equivalent to immunization by needle. Hepatitis A vaccine is equally potent when given with hepatitis B vaccine. Data on rapid immunization schedules and efficacy are under evaluation. We conclude that hepatitis A vaccine is a major improvement in our ability to prevent hepatitis A in soldiers.

Clinical and laboratory observations following oral or intramuscular administration of a live attenuated hepatitis A vaccine candidate.

Clinical observations made after immunising volunteers with a live attenuated hepatitis A vaccine are described. The candidate vaccine was prepared with the HM175 strain of hepatitis A virus and shown to be safe, immunogenic and efficacious in experimental animals. When the candidate vaccine was tested by oral administration in humans at increasing doses--10(4), 10(5), 10(6) and 10(7) median tissue culture infective doses (TCID50)--an antibody response was not observed at any dose. Volunteers who received similar doses by the intramuscular route developed antibody to hepatitis A three weeks after immunization with 10(6) or 10(7) TCID50. The antibody response was sustained for the 12 weeks of the observation period. All volunteers remained healthy with normal results from liver tests throughout the monitoring period. Further clinical observations of this product are in progress.

Post-Transfusion Viral Hepatitis and the TTVS

From the mid-1940s until the 1960s, studies of post-transfusion viral hepatitis focused on prevention by immune serum globulin. The value of globulin in transfusion hepatitis is still to be determi...

The military and hepatitis B

Hepatitis B virus (HBV) is an important cause of morbidity in military forces. HBV threatens a safe blood supply for mass casualties, contributes to rising health care costs and presents an occupational risk to health care workers. The susceptibility of soldiers reflects that of other residents of their country of origin. In intermediate and high-prevalence regions, infections usually occur in young adults and follow exposure to an HBV carrier through blood or sexual contact. Control of HBV infections must rely on education regarding risk factors, screening of blood donors and immunization. Military populations provide unique opportunities for studying the epidemiology of hepatitis B and carrying out mass vaccination programmes.

Human hypersensitivity to a sham vaccine prepared from mosquito-cell culture fluids

A sham vaccine, prepared with the C6/36 cell line derived from larval Aedes albopictus mosquitoes, was skin tested on 12 volunteers. Although no reactions were observed after prick tests, three immediate reactions did occur after intradermal tests. Subcutaneous administration of the C6/36 sham vaccine was initially performed on the nine subjects who did not demonstrate immediate reactions. Five of these subjects developed delayed reactions at the site of the intradermal test within 12 hr after inoculation. A Prausnitz-Küstner test was performed on the back of one unsensitized subject by use of both unheated and heated sera from three subjects who had immediate skin reactions, three who demonstrated a delayed reaction, and one who had a negative skin response. In the Prausnitz-Küstner test, immediate skin reactions were observed with all seven unheated sera but with none of the heated serum aliquots. The determination that skin reactivity was associated with a heat-labile serum factor suggested the mechanism was IgE-mediated. Under close surveillance, the C6/36 sham vaccine was administered subcutaneously to one volunteer who had previously demonstrated an immediate response. This subject developed an anaphylactic reaction characterized by hives at the site and more distantly from the site of the subcutaneous inoculation. Hypersensitivity to A. albopictus larval antigens is common and precludes the use of C6/36 cell culture as a substrate for viral vaccines.

Transmission of Hepatitis B Virus

Excerpt To the editor: The article by Reiner and associates in the February issue (1) presents evidence to support de facto parenteral transmission as a source of hepatitis B virus (HBV) infections...

Absence of leukocytes permissive to dengue 2 virus in the acute phase of dengue hemorrhagic fever.

Patients with primary dengue infection developed dengue 2 virus (D2V) permissive peripheral blood leukocytes (PBL) 2--3 weeks after infection. PBL from healthy individuals with dengue antibody were permissive to D2V in vitro, suggesting that immunologically mediated in vitro D2V permissiveness persists for a relatively long time after recovery from dengue infection. However, PBL obtained from second infection dengue hemorrhagic fever patients did not support D2V growth during the acute phase of illness but did so during convalescence. Leukocytes from dengue-immune patients with typhoid fever or non-dengue viral illness were permissive throughout both acute and convalescent phases of illness although there was tendency for increased permissiveness during convalescence. Acute phase PBL from DHF patients synthesized and secreted dengue neutralizing antibody in culture. Absence of D2V replication in these cultures was strongly, but not completely, correlated with antibody production. Other immunological mechanisms, in addition to antibody, may be operating in vitro or in vivo during acute phase dengue hemorrhagic fever to alter the permissiveness of PBL to D2V infection.