Vaccine

Role of long-persisting human hepatitis E virus antibodies in protection.

Year 1998
Chauhan A. Dilawari JB. Sharma R. Mukesh M. Saroa SR.
Molecular Biology, International Centre for Genetic Engineering and Biotechnology, Trieste, Italy.
The role of long-persisting HEV antibodies in humans was investigated. A well-characterized human volunteer anti-HEV (IgG) after 4 years of the recovery of the disease was passively immunized (200 mg kg-1 body wt) intramuscularly into three rhesus monkeys (nos 7, 8 and 9), while two monkeys (nos 5 and 6) were injected with normal immunoglobulin preparation (negative for anti-HEV IgG). At 16 h later all the animals were challenged intravenously with live HEV, as 10% stool extract prepared from the volunteer (positive for HEV by solid-phase immune electron microscopy). It was seen that transaminases (ALT/AST) were elevated in immunized monkeys on day 49 (no. 8), 60 (no. 7) and 86 (no. 9) after the virus challenge. On serological examination, all immunized (nos 7, 8 and 9) and one unimmunized (no. 6) monkeys were found positive for HEV IgM on day 10 post-challenge, while monkey no. 5 was negative. Further, all the animals from the immunized and unimmunized group seroconverted to HEV-IgG when tested on days 25 and 55 post-challenge. This has clearly shown that there is no protection. Therefore, these long-persisting HEV antibodies alone in humans, may not be protective in passive immunization.

Combined intramuscular-intradermal protocol of universal neonate HB vaccination irrespective of mothers status of HBsAg.

Year 1998
Yao FB. Li XX. Du YX. Ye SL.
Department of Pediatrics, Xuzhou Medical College, Jiangsu, People's Republic of China.
To evaluate a protocol of combined intramuscular-intradermal (i.m.-i.d.) universal hepatitis B (HB) vaccination of neonates regardless of the mothers' HB surface antigen HBsAg status, 160 full-term newborn babies were sequentially divided into groups A and B (test and control groups). The group A babies were immunized by giving 30 micrograms HB vaccine i.m. within 24 h after birth and 2 micrograms i.d. twice at 1 and 6 months of age. Group B babies were immunized by giving one initial dose of 30 micrograms i.m. and two booster doses of 10 micrograms i.m. after same 0, 1, 6-month schedule. Blood samples were collected at birth before the first dose of the HB vaccine, at 6 months of age before the third dose and at 12 months. The blood samples were tested for HBsAg and anti-HBs by using Abbott RIA reagents. All of the 160 newborns received three doses of vaccine, but in only 96 of them was the blood examination completed. The positive rate of anti-HBs > 10 IU l-1 was 76.27 and 83.08% in groups A and B, respectively at 6 months, and 83.72 and 92.45%, respectively at 12 months. The geometric mean titres (GMT) of anti-HBs was 42.25 and 60.25 IU l-1 in groups A and B, respectively at 6 months, and 74.45 and 87.1 IU l-1, respectively at 12 months. HBsAg was negative in the two groups 6 and 12 months after birth. The chi 2 and t-tests showed there were no significant differences in these data between the two groups. Thus was it demonstrated that the combined i.m.-i.d. protocol using 34 micrograms of HB vaccine can produce a protection similar to that of the conventional 50 micrograms i.m. regimen, while ca on-third of the vaccine can be saved. The new protocol is theoretically rational and may be ideal according to the cost-effectiveness principle.

Adverse impact of infections on antibody responses to measles vaccination.

Year 1998
Migasena S. Simasathien S. Samakoses R. Pitisuttitham P. Heath J. Bellini W. Bennett J.
Vaccine Trial Centre, Mahidol University, Bangkok, Thailand.
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.

Mutations in the a determinant of hepatitis B surface antigen among Chinese infants receiving active postexposure hepatitis B immunization.

Year 1998
He JW. Lu Q. Zhu QR. Duan SC. Wen YM.
Department of Molecular Virology, Shanghai Medical University, People's Republic of China.
Twenty-four infants who became positive to the surface antigen of hepatitis B virus (HBsAg) despite a complete course of active postexposure immunization with plasma derived hepatitis B vaccine were studied. The polymerase chain reaction amplified products of the common neutralizing epitope 'a' determinant of HBsAg (Nucleotide 419-598) from serum samples were sequenced and analyzed for nucleotide mutations. Four cases (16.7%) had mutations that led to amino acid substitutions between codons 124 and 147. Only one case (N1) showed a substitution at codon 145 (from glycine to arginine, 145R), the other three were at codons 126-129. The mother of N1 was co-infected with the wild type and the mutant virus. Five years later, serum of N1 showed only the wild type virus. There was no significant relationship between the mutation rate and the anti-HBs response to hepatitis B vaccination. Results suggest that without immune selective pressure, 145R variant was not frequently observed, and was not stable. Mutation in the 'a' determinant was not an important cause of failure to prevent maternal-infant transmission of HBV by active postexposure hepatitis B immunization in Chinese children.

Major adverse reactions to yeast-derived hepatitis B vaccines--a review.

Year 1998
Grotto I. Mandel Y. Ephros M. Ashkenazi I. Shemer J.
Israel Defense Force, Medical Corps, Israel.
Yeast-derived recombinant DNA hepatitis B vaccines usage became widely accepted since the early 1990s. Severe adverse events have been reported infrequently in adults and rarely in infants and children given hepatitis B vaccine in the ten years which have passed since the introduction of the vaccine. Some of the data were summarized in previous review articles. Our review of the literature revealed reports of serious adverse reactions which included immediate reactions (anaphylaxis and urticaria) as well as delayed reactions, including skin, rheumatic, vasculitic (including Systemic Lupus Erythematosus and glumerulonephritis), hematologic, ophthalmologic and neurologic reactions. These cases were summarized and a pathogenetic mechanism is offered.

Safety and immunogenicity of live, attenuated human rotavirus vaccine 89-12.

Year 1998
Bernstein DI. Smith VE. Sherwood JR. Schiff GM. Sander DS. DeFeudis D. Spriggs DR. Ward RL.
Gamble Program for Clinical Studies, Division of Infectious Diseases, Children's Hospital Medical Center, Cincinnati, OH 45229-3039, USA.
The safety and immunogenicity of an orally administered live human rotavirus vaccine candidate (89-12), attenuated by 33 passages in monkey kidney cells, were evaluated in placebo-controlled trials in adults, children and infants. This strain was selected because natural infections with 89-12-like rotaviruses provided 100% protection over two years. The initial evaluations in adults, seropositive children and nine infants indicated that the vaccine was safe. Two doses of vaccine (10(5) p.f.u. dose-1) or placebo were then given to 42 infants, aged from 6 to 26 weeks. No significant difference in side effects was seen. Seroconversion was demonstrated in 19 of 20 previously uninfected vaccine recipients, but > or = 4-fold rises in 89-12 neutralizing antibody titers were detected in only seven subjects. Intestinal IgA responses were detected in 15 subjects. This attenuated human rotavirus was safe and immunogenic and should be further evaluated as a vaccine candidate.

Revaccination against hepatitis B virus of non-responding and low-responding infants immunised at birth. A parallel evaluation of rubella and tetanus vaccine.

Year 1998
Belloni C. Tinelli C. Orsolini P. Pistorio A. Avanzini A. Moretta A. Gulminetti R. Bogliolo O. Chirico G. Rondini G.
Division of Neonatal Intensive Care, IRCCS Policlinico San Matteo, Pavia, Italy.
The aim of the present study was to identify the true extent of the non-responsiveness in infants born from HBsAg-negative mothers, vaccinated against Hepatitis B Virus (HBV) at birth. Sixty-four non- and low-responding infants, selected from an initial cohort of 2009, were given two additional doses of recombinant HBV vaccine between the tenth and the twelfth month of age. A parallel evaluation was conducted on the response to anti-rubella and anti-tetanus vaccine. Only two infants remained non-responders, whereas 68% of the non-responders and 94% of the low responders after the primary vaccination schedule developed antibody titres over 100 mIU ml-1. No significant relationship between the specific antibody level against HBV and against rubella or tetanus 1 month after vaccination was observed.

Ad hoc survey of hepatitis B vaccination campaign in newborns of HBsAg positive mothers and in 12-year-old subjects in southern Italy.

Year 1998
Adamo B. Stroffolini T. Sagliocca L. Simonetti A. Iadanza F. Fossi E. Tancredi F. Mele A.
Epidemiology Unit, AUSL, Napoli, Italy.
The ongoing vaccination campaign against hepatitis B (HB) for newborns of hepatitis B surface antigen (HBsAg) positive mothers and for 12-year-old subjects was evaluated in Naples, Italy, an area of relatively high HB endemicity. Subjects were recruited by a random sampling procedure. Among 2060 pregnant women studied, 1887 (91.6%) were screened for HBsAg. HBsAg prevalence was 2.5% (47/1887). Immunoprophylaxis according to the protocol (immunoglobulins within 24 h plus vaccine within 7 days after birth) was administered in 26 (55.3%) out of the 47 newborns of HBsAg positive mothers; vaccination was delayed (later than 7 days after birth) for 14 (29.8%) infants; in the remaining seven newborns (14.9%) were not given immunoglobulins at birth. All infants were vaccinated. Out of the 1000 adolescents sampled 130 (13%) were not found due to an inaccurate census list; 727 (83.3%) of the 870 investigated had received a three-dose HB vaccine series. Overall, the HB vaccination program in Italy is working well. However, further efforts should be made to improve the efficacy and effectiveness of the campaign.