Anti-HBs levels in infants of hepatitis B carrier mothers after delayed active immunization with recombinant vaccine concomitant with DTP-polio vaccine: Is there need for a second dose of HBIg?

The need for an additional dose of hepatitis B immune globulin (HBIg) was studied by comparing infants receiving 1 ml HBIg at birth followed by hepatitis B immunization, concomitant with DTP-polio vaccine, at 3, 4, 5 and 11 months (schedule E), with infants receiving the same schedule with additional HBIg at 3 months (schedule F). The immune response to recombinant hepatitis B vaccine (20 μg) was evaluated in 195 infants born to HBsAg-positive mothers allocated to groups E and F and compared with historic controls who received plasma vaccine (10 μg) according to schedule F. Blood samples were drawn at 0, 3, 4, 6, 11, 12 and 24 months of age. No difference in efficacy between the two schedules was observed; 8 and 6% of infants born to HBeAg-positive HBsAg carrier mothers in groups E and F, respectively, became HBsAg carriers. Passively acquired antibodies at birth remained present for about 5 months in most infants. The seroprotection rates (anti-HBs ⩾ 10 IU l−1) were over 90% at all time points and similar for groups E and F. The titres of anti-HBs attained during the first 6 months were statistically lower (p ⩽ 0.02) for group E than for group F but similar thereafter. Anti-HBs titres in infants receiving the recombinant vaccine were significantly lower than in infants receiving the plasma vaccine (p ⪡ 0.001). Supplemental doses of HBIg in infants receiving a high dose of HBIg (> 200 IU) at birth and the first dose o

Immunogenicity of two different dosages (10 and 5 μg) of recombinant DNA hepatitis B vaccine in healthy neonates

The immunogenicity of a half (5 μg) and a full (10 μg) dosage of recombinant DNA yeast-derived hepatitis B vaccine (HB-Vax-DNA) in healthy neonates was assessed in order to compare two candidate dosages of vaccine. After randomization 174 newborns of HBsAg-negative mothers entered the study. Neonates received four doses of either 10 or 5 μg hepatitis B vaccine, according to the DTP polio immunization schedule at months 3, 4, 5 and 11. No serious adverse reactions were observed; 15.5% of vaccinated newborns suffered mild transient local symptoms. The vaccine was highly immunogenic irrespective of dosage of vaccine; all infants developed anti-HBs levels ⩾ 10 IUl−1, 99% ⩾ 100 IUl−1. A dosage of 10 μg hepatitis B vaccine produced higher antibody levels than 5 μg hepatitis B vaccine after primary vaccination (first three doses) but not after booster vaccination (fourth dose) (p = 0.06 and 0.75, respectively). Either vaccine dosage can be recommended for incorporation in the Expanded Programme on Immunization in the Netherlands

In vivo activity of a mixture of two human monoclonal antibodies (anti-HBs) in a chronic hepatitis B virus carrier chimpanzee

A 35-year-old female hepatitis B virus carrier chimpanzee was infused with one dose of a mixture of human monoclonal antibodies 9H9 and 4-7B (antibodies against hepatitis B virus surface antigen; HBsAg). Blood samples were taken before and up to 3 weeks after infusion. HBsAg and antibodies against HBsAg (anti-HBs) were quantified by radioimmunoassay and enzyme immunoassay. Free anti-HBs was never detected. Thirty min after the start of the infusion the HBsAg level was minimal with maximum loading of the chimpanzee HBsAg with human immunoglobulin. HBsAg complexes could be dissociated by acid treatment. The HBsAg level was completely restored on day 7. Similar results were obtained for the preS1-containing particles that may represent the infectious viral particles in the chimpanzee serum. A mouse monoclonal anti-HBs (HBs.OT40) was found to compete with 9H9 in artificial immune complexes with the pre-treatment HBsAg from the chimpanzee. Used as a conjugate, HBs.OT40 yielded a maximum decrease in the signal in the 30 min sample compared to non-competing anti-HBs conjugates. This indicates binding of HBsAg with 9H9 in the circulation of the chimpanzee. Immune-complexed 4-7B could not be detected by its corresponding 4-7B peptide conjugate, probably due to its low concentration in the complexes. It is concluded that human monoclonal anti-HBs can effectively reduce the level of HBsAg in serum from this chronic carrier. Monoclonals 9H9 and 4-7B may complement each other due to their different mechanisms of inactivation, probably with higher efficiency than that monitored by our HBsAg screening assays

Transplacentally Acquired Maternal Antibody against Hepatitis B Surface Antigen in Infants and its Influence on the Response to Hepatitis B Vaccine

BACKGROUND: Passively acquired maternal antibodies in infants may inhibit active immune responses to vaccines. Whether maternal antibody against hepatitis B surface antigen (anti-HBs) in infants may influence the long-term immunogenicity of hepatitis B vaccine remains unknown. METHODOLOGY/PRINCIPAL FINDINGS: Totally 338 pairs of mothers and children were enrolled. All infants were routinely vaccinated against hepatitis B based on 0-, 1- and 6-month schedule. We characterized the transplacental transfer of maternal anti-HBs, and compared anti-HBs response in children of mothers with or without anti-HBs. In a prospective observation, all 63 anti-HBs positive mothers transferred anti-HBs to their infants; 84.1% of the infants had higher anti-HBs concentrations than their mothers. One and half years after vaccination with three doses of hepatitis B vaccine, the positive rate and geometric mean concentration (GMC) of anti-HBs in 32 infants with maternal anti-HBs were comparable with those in 32 infants without maternal antibody (90.6% vs 87.5%, P = 0.688, and 74.5 vs 73.5 mIU/ml, P = 0.742, respectively). In a retrospective analysis, five and half years after vaccination with three doses vaccine, the positive rates of anti-HBs in 88 children of mothers with anti-HBs ≥1000 mIU/ml, 94 children of mothers with anti-HBs 10-999 mIU/ml, and 61 children of mothers with anti-HBs <10 mIU/ml were 72.7%, 69.2%, and 63.9% (P = 0.521), respectively; anti-HBs GMC in these three groups were 38.9, 43.9, and 31.7 mIU/ml (P = 0.726), respectively. CONCLUSIONS/SIGNIFICANCE: The data demonstrate that maternal anti-HBs in infants, even at high concentrations, does not inhibit the long-term immunogenicity of hepatitis B vaccine. Thus, current hepatitis B vaccination schedule for infants will be still effective in the future when most infants are positive for maternal anti-HBs due to the massive vaccination against hepatitis B

Pros and Cons of Peginterferon Versus Nucleos(t)ide Analogues for Treatment of Chronic Hepatitis B

The emergence of new and more potent treatment options has markedly changed the treatment landscape of chronic hepatitis B. Both peginterferon and nucleos(t)ide analogues have considerable advantages and limitations, and current treatment guidelines refrain from clearly suggesting a first-line treatment option. Peginterferon offers the advantage of higher sustained response rates in both hepatitis B early antigen (HBeAg)-positive and HBeAg-negative patients, at the price of considerable side effects and high costs. Nucleos(t)ide analogues offer easy daily oral dosing, and newly registered agents can maintain viral suppression for prolonged treatment duration. However, relapse is common after therapy discontinuation and extended therapy therefore often necessary. Prolonged treatment with nucleos(t)ide analogues may enhance chances of virologic and serologic response at the potential cost of the emergence of viral resistance and side effects. Baseline and on-treatment prediction of response may help select patients for peginterferon therapy and can aid individualized treatment decisions concerning therapy continuation or discontinuation

Pros and cons of different therapeutic antibody formats for recombinant antivenom development.

Antibody technologies are being increasingly applied in the field of toxinology. Fuelled by the many advances in immunology, synthetic biology, and antibody research, different approaches and antibody formats are being investigated for the ability to neutralize animal toxins. These different molecular formats each have their own therapeutic characteristics. In this review, we provide an overview of the advances made in the development of toxin-targeting antibodies, and discuss the benefits and drawbacks of different antibody formats in relation to their ability to neutralize toxins, pharmacokinetic features, propensity to cause adverse reactions, formulation, and expression for research and development (R&D) purposes and large-scale manufacturing. A research trend seems to be emerging towards the use of human antibody formats as well as camelid heavy-domain antibody fragments due to their compatibility with the human immune system, beneficial therapeutic properties, and the ability to manufacture these molecules cost-effectively