Sricharoen Migasena

Phase I/II study of a candidate vaccine designed against the B and E subtypes of HIV-1.

SummaryA 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 μg 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.

Simultaneous administration of oral rhesus-human reassortant tetravalent (RRV-TV) rotavirus vaccine and oral poliovirus vaccine (OPV) in Thai infants

Rhesus-human reassortant tetravalent (RRV-TV) oral rotavirus vaccine was given at the same time as oral poliovirus vaccine (OPV) or inactivated parenteral poliovirus vaccine (IPV) to Thai infants at 2, 4 and 6 months of age. Sera for rotavirus antibody studies were taken prior to and one month after each vaccination. After the first dose of vaccine at 2 months of age, 37% of the infants receiving rotavirus vaccine with IPV but only 10% of those receiving it with OPV showed a seroconversion by rotavirus IgA ELISA antibody test (p < 0.001). Likewise, neutralizing antibody seroconversion rates in initially seronegative subjects to rhesus rotavirus type 3 (RRV-3) after the first dose of RRV-TV vaccine were higher if the vaccine was given with IPV (74%) than if given with OPV (39%) (p = 0.0069). After the second and third doses of vaccine, the rotavirus IgA ELISA and RRV-3-neutralizing antibody response rates were not different between groups. Development of neutralizing antibodies to human rotavirus serotypes 1, 2 and 4 in the first seven months of life in vaccinees receiving rotavirus vaccine with OPV tended to occur at a lower rate than in those receiving rotavirus vaccine with IPV but the antibody levels were not significantly different at 7 months of age. Poliovirus type 2 and type 3 antibody responses were not different in infants receiving the rotavirus vaccine with OPV as compared with infants receiving only OPV. The mean poliovirus type 1 antibody level was slightly but not significantly lower at 5 and 7 months of age in infants that received both rotavirus vaccine and OPV.(ABSTRACT TRUNCATED AT 250 WORDS)

AIDSVAX (MN) in Bangkok injecting drug users: a report on safety and immunogenicity, including macrophage-tropic virus neutralization.

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.

Seroprevalence of varicella-zoster virus antibody in Thailand

Abstract Objective: To determine the seroprevalence of varicella-zoster virus antibodies in a wide age range of healthy subjects in Thailand. Design and Methods: In 1994, blood samples were collected from 559 volunteers aged 4 months to 77 years from the Bangkok area; questionnaires about socioeconomic background and history of chickenpox or herpes zoster were also completed. Serum samples were assayed for specific varicella-zoster virus (VZV) IgG antibodies using a commercial enzyme-linked immunosorbent assay kit. Results: The seroprevalence rate (61.4% overall) increased with age: less than 1 year, 10.2%; 1 to 4 years, 24.1 %; 5 to 9 years, 62.5%; 10 to 14 years, 70.4%; 15 to 19 years, 78.9%; 20 to 29 years, 69.2%; 30 to 39 years, 96.1 %; 40 to 49 years, 100%; and 50 years and older, 98.0%. No significant differences in the VZV antibody prevalence with respect to gender, family size, or family income were seen. There was good correlation between varicella history and seropositivity: 92.9% of subjects with a varicella history were seropositive. Conclusions: In this urban population, approximately one in three adolescents and young adults lacked natural immunity against varicella. The results suggest that vaccination programs in Thailand and probably other tropical countries should include susceptible adolescents and adults who are at high risk of developing severe varicella and resultant complications.

Vaccination of Thai infants with rhesus-human reassortant tetravalent oral rotavirus vaccine

In a randomized double blind placebo-controlled study, the rhesus-human reassortant tetravalent oral rotavirus vaccine (dose 4 x 10(4) plaque-forming units) was evaluated in Thai infants immunized at ages 2, 4 and 6 months. To investigate dose responses and to compare vaccine-induced and naturally acquired rotavirus immunity in the study population blood specimens were collected before and 1 month after each vaccination and at 12 months of age. No adverse reactions attributable to the vaccine were detected in the vaccinees. Sixty-three of 94 (67%) vaccine recipients showed a seroconversion in rotavirus IgA enzyme-linked immunosorbent assay antibodies after one or more doses, whereas only 15 of 93 (16%) placebo-vaccinated control children showed an IgA enzyme-linked immunosorbent assay antibody response, suggestive of natural rotavirus infection, between 2 and 7 months of age. By measuring rhesus rotavirus-neutralizing antibodies a seroconversion was detected in 49% of the vaccinees and 14% of the controls between 2 and 7 months of age. The geometric mean titers of neutralizing antibodies to human rotavirus serotypes 1, 2, 3 and 4 after the completion of vaccinations and at 12 months of age were higher in the vaccinees than in the controls. It is concluded that, even though maternally acquired rotavirus antibodies are commonly present, the rhesus-human reassortant tetravalent vaccine is immunogenic in many Thai infants ages 2 to 6 months. The immunogenicity of this vaccine is enhanced by multiple doses.

Measles vaccination of Thai infants by intranasal and subcutaneous routes : possible interference from respiratory infections

Reactogenicity and seroresponses were studied after standard doses of Edmonston-Zagreb measles vaccine were given intranasally (i.n.) and subcutaneously (s.c.) to 6-month-old Thai children. Few children given i.n. vaccine (2/31), but most (13/21) given s.c. vaccine, seroconverted. All but 1 of 51 children were seropositive after receiving vaccine s.c. at 9 months-of-age. Upper respiratory infection (URI) outbreaks with onsets in the week following vaccination occurred after each vaccination session and were equally common in all groups. URIs following i.n. vaccination at 6 months may have adversely affected response to i.n. vaccine, while URIs after s.c. vaccination at 9 months adversely affected final geometric mean antibody titers. I.n. measles vaccination does not appear to be an acceptable route for routine vaccination.

Comparison of Enhanced Potency Inactivated Poliovirus Vaccine (EIPV) Versus Standard Oral Poliovirus Vaccine (OPV) in Thai Infants

Enhanced potency inactivated poliovirus vaccine (EIPV), combined with diphtheria-tetanus-pertussis (DTP) vaccine, was compared with oral poliovirus vaccine (OPV) regarding immunogenicity in Thai infants, vaccinated at 2, 4 and 6 months of age. EIPV induced significantly higher seroconversion rates than OPV to all 3 poliovirus types after the second and third immunization. After 3 doses of each vaccine, at 7 months of age, all infants receiving EIPV proved seropositive for poliovirus type 1, type 2 and type 3 neutralizing antibodies, whereas of those receiving OPV, 9% remained seronegative (titre < 1:4) for type 1 (p = 0.0042) and 11% for type 3 (p = 0.0013). All participating children were given an additional dose of OPV at the age of 9 months and tested again at 12 months of age. At that point, virtually all infants had poliovirus neutralizing antibodies, but the geometric mean titres to each poliovirus type were significantly higher in the vaccinees who had received EIPV. It is concluded that the greater immunogenicity of EIPV vis-à-vis 3 doses of OPV may be biologically significant for protection against poliovirus types 1 and 3 in countries where cases of poliomyelitis occur in young children. These findings warrant considering EIPV, alone or in combination with OPV, for an immunization programme in Thailand and similar countries in the future.

Adverse impact of infections on antibody responses to measles vaccination.

Antibody titres were determined in 102 Thai infants who were vaccinated at 9-months of age during the respiratory disease season. The symptom densities of illnesses at or following vaccination, including rhinorrhea and diarrhea, were significantly lower among seroconverters, although the simple presence or absence of specific symptoms was not significantly related to seroconversions. Logistic regression indicated that neutralization test antibody titres below the median titre of 1:80 following vaccination were significantly more frequent among those with rhinorrhea when vaccinated and among those with diarrhea after vaccination. Compared with a referent group without these symptoms, titres were lower in those who had rhinorrhea when vaccinated, rhinorrhea during the first week post vaccination, and diarrhea in either of the two follow-up weeks. Illnesses concurrent or subsequent to measles vaccination adversely affected antibody responses in these study objects.

SPf66 malaria vaccine is safe and immunogenic in malaria naive adults in Thailand

In preparation for an efficacy trial of malaria vaccine SPf66 in Thailand, a series of overlapping Phase I trials were conducted of US-manufactured SPf66. Here, two clinical lots were evaluated for safety and immunogenicity in a combined open-label trial. Eleven healthy, malaria naive, 18-44 year-old Thai men and women received three doses by subcutaneous injection in alternate arms at 0, 1 and 6 months. Safety was assessed by monitoring local and systemic reactogenicity and laboratory parameters. Common side effects were mild erythema, induration and tenderness at the site of injection which resolved within 24-48 h. At third immunization, two volunteers developed acute bilateral reactions with induration, erythema and pruritus limited to the sites of the second and third immunizations. Eight of 11 volunteers sero-converted by ELISA, six of whom would be classified as high responders by Colombian standards. Eight of 11 volunteers developed a lymphoproliferative response to the SPf66 antigen. Side effects were more common and antibody and lymphoproliferative responses greatest, among the four female volunteers. This initial study of SPf66 malaria vaccine in Asia constitutes an essential link between the initial Phase I study in the US and subsequent field studies in a semi-immune population in a malaria endemic area of Thailand. This study further establishes comparability of US-manufactured SPf66 with that of Colombian provenance and substantiates the validity of the subsequent negative efficacy results of SPf66 in a field trial in Thailand.

Clinical and bacteriological studies of El Tor cholera after ingestion of known inocula in Thai volunteers

Twenty-six healthy adult Thai volunteers were recruited for clinical and bacteriological studies of cholera induced by oral inoculation with Vibrio cholerae El Tor Inaba strain N16961. Vibrio dosages of 0.3 x 10(4), 1.6 x 10(5) and 1.9 x 10(6) c.f.u. were given to three groups of five volunteers, and 2.0 x 10(7) c.f.u. to 11 volunteers. Diarrhoeal attack rates correlated positively with the size of the inocula (p less than 0.01). It was estimated that a diarrhoeal attack rate of 90% (ED90) would be achievable by inoculation of 1.3 x 10(7) c.f.u. of the organisms. There were no significant differences between the groups in the latent period to positive stool culture, maximum vibrio count per gram of stool and duration of stool positivity. The ED90 of V. cholerae obtained may be used as a challenge dose in subsequent studies on protective efficacy of cholera vaccines in Thai adult volunteers.