Attenuated Vibrio cholerae oral vaccineCVD 103-HgR was welltolerated by 324 Thai soldiers and civilians. Most receiveda single 5 X 10 8 cfu dose, while 40 each receivedone or two 5 X 10 9 cfu doses. Vibriocidal antibody (the best correlate of immunity) seroconversion was lower in soldiers than civilians (P < .001). Increasing the vaccinedose to 5 X 10 9 cfu raised the geometric mean titer (P < .001). A second 5 X 10 9 cfu dose one week later did not notably increase seroconversions. Likelihood of seroconversion was inverselycorrelated with baseline vibriocidal titer (P < .001). CVD 103-HgR caused seroconversion in most subjects with baseline titers .;;1:40, including 100% of civilians after one 5 X 10 8 cfu dose, 79% of soldiers after one 5 X 10 9 cfu dose, and 45% of soldiers after one 5 X 10 8 cfu dose. In persons with elevatedbaseline titers, vibriocidal antibody seroconversion is not a sensitive measure of whether vaccine has boosted intestinal immunity; for such subjects,other measurements must be used. Study regimens in endemic areas should use a single 5 X 10 9 cfu dose.Cholera remains an important public health problem in less-developed countries, spreading readily where sanitation is compromised and often appearing in explosive epidemics. The World Health Organization has targeted the development of an improved cholera vaccine as a priority [I, 2] because the parenteral inactivated whole cell vaccine, which provides only limited, short-lived protection, can play no practical role in cholera control [3]. An ideal new cholera vaccine would be well tolerated and rapidly stimulate a high level of long-term protection among all age groups after administration ofjust one oral dose. Such a vaccine would constitute a welcome addition to the public health intervention measures available to control epidemic and endemic cholera.An important advance in immunization against cholera was documented several years ago in a field trial in BanglaReceived 6 November 1991; revised 14 January 1992. The clinical protocol followed the guidelines of the Department of Health and Human Services and was reviewed by ethical committees at the University of Maryland at Baltimore. Mahidol University. and the US Department of the Army. The studies were explained in detail, and written informed consent was obtained.Grant desh when two related inactivated oral cholera vaccines (one consisting of inactivated Vibrio cholerae 0 I organisms and the other of inactivated organisms plus the B subunit ofcholera toxin) were each shown to confer 50% protection for 3 years [4]. That experience illustrates that oral vaccines can elicit relatively long-lived protection against cholera. However, the field trial in Bangladesh also exposed notable deficiencies of those oral inactivated vaccines: Multiple, spaced doses were required to elicit protection, young children (the population with the highest incidence ofcholera in that area) were least protected, and despite administration of three spaced doses, the level of efficacy was only 50%-52% [4].With a...

A phase I/II trial of a candidate vaccine to prevent HIV infection was carried out in Bangkok, Thailand, testing AIDSVAX B/E (VaxGen, Inc., Brisbane, CA), a bivalent subunit vaccine prepared by combining recombinant gp120 from a subtype B virus (HIV-1MN) with gp120 from a subtype E virus (HIV-1A244) in alum adjuvant. The studies provide human data on the immunogenicity of various dose combination of non-subtype B vaccine antigens. The results suggest that AIDSVAX B/E is safe and immunogenic in humans. The optimal dose for humans in developing countries was 300 microg of each antigen (B and E). Clade E responses were measurably increased by immunizing with gp120 B/E over B alone. Using the B/E combination did not interfere with the response to either clade. Antibodies to AIDSVAX B/E were able to bind to oligomeric gp120 on the surface of cells infected with primary isolates of HIV-1.

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A randomized, double-blind, placebo-controlled phase I/II study of AIDSVAX (MN) was conducted among injecting drug users in Bangkok, Thailand. Four doses of vaccine (300 microg of MN-rgp120 in alum) or placebo (alum) were given at study entry and at 1, 6, and 12 months. The objectives of the study were to evaluate (1) the feasibility of conducting vaccine trials in this population; (2) the safety of this candidate AIDS vaccine; and (3) the immunogenicity of this vaccine. Thirty-three volunteers (22 vaccine and 11 placebo recipients) were recruited. None were lost to follow-up during the 18-month study. Mild reactogenicity was noted, which was similar in both vaccine and placebo recipients. The vaccine induced anti-HIV-1 antibody in all vaccine recipients. Maximal titers of binding antibodies of MN-rgp120 and the V3 domain of MN-rgp120 were induced after the third (6 month) dose while maximal neutralizing antibodies followed the fourth (12 month) dose. The vaccine-induced antibodies from several volunteers were capable of neutralizing macrophage-tropic, subtype B viruses (301660 and JRCSF) detected in a PBMC-based assay. Binding and neutralizing antibodies declined about 10-fold in the 6 months after the last boost. Two vaccinees became infected during the trial, both with subtype E viruses. A phase III efficacy trial, using a bivalent gp120 vaccine containing antigens from a subtype B virus (MN) and a subtype E virus (A244), was initiated in March 1999 in injecting drug users in Bangkok.

A single dose (5 x 108 organisms) of attenuated A-B' Vibrio cholerae classical Inaba recombinant vaccine strain CVD 103-HgR or placebo was administered to 24 healthy young Thai adults in a randomized, placebo-controlled, double-blind trial of safety and immunogenicity. None of the volunteers experienced untoward reactions. The vaccine strain was recovered from 2 of 12 vaccinees. The vibriocidal antibody response (the best immunological correlate of protection) was good: 11 of 12 vaccinees (92%) manifested significant serotype-homologous Inaba antibody rises with a peak reciprocal geometric mean titer (RGMT) postvaccination of 3,417; 9 of 12 exhibited significant serotype-heterologous Ogawa antibody rises (prevaccination RGMT, 180; peak RGMT, 2,874). Nine of 12 vaccinees had significant rises in serum antitoxin. None of the controls exhibited rises in vibriocidal or antitoxic antibody. This preliminary study further confirms the safety and immunogenicity of CVD 103-HgR live oral cholera vaccine and paves the way for larger community zation with a combined B subunit/whole cell vaccine. J. Infect.