The origins of HBV are unclear. The new orthohepadnavirus species from Brazilian capuchin monkeys resembled HBV in elicited infection patterns and could infect human liver cells using the same receptor as HBV. Evolutionary analyses suggested that primate HBV-related viruses might have emerged in African ancestors of New World monkeys millions of years ago. HBV was associated with hominoid primates, including humans and apes, suggesting evolutionary origins of HBV before the formation of modern humans. HBV genotypes found in American natives were divergent from those found in American monkeys, and likely introduced along prehistoric human migration. Our results elucidate the evolutionary origins and dispersal of primate HBV, identify a new orthohepadnavirus reservoir, and enable new perspectives for animal models of hepatitis B.

Nucleic acid polymers (NAPs) block the release of HBsAg from infected hepatocytes. These compounds have been previously shown to have the unique ability to eliminate serum surface antigen in DHBV-infected Pekin ducks and achieve multilog reduction of HBsAg or HBsAg loss in patients with chronic HBV infection and HBV/HDV coinfection. In ducks and humans, the blockage of HBsAg release by NAPs occurs by the selective targeting of the assembly and/or secretion of subviral particles (SVPs). The clinically active NAP species REP 2055 and REP 2139 were investigated in other relevant animal models of HBV infection including woodchucks chronically infected with WHV, HBV transgenic mice and HBV infected SCID-Hu mice. The liver accumulation of REP 2139 in woodchucks following subcutaneous administration was examined and was found to be similar to that observed in mice and ducks. However, in woodchucks, NAP treatment was associated with only mild (36-79% relative to baseline) reductions in WHsAg (4/10 animals) after 3-5 weeks of treatment without changes in serum WHV DNA. In HBV infected SCID-Hu mice, REP 2055 treatment was not associated with any reduction of HBsAg, HBeAg or HBV DNA in the serum after 28 days of treatment. In HBV transgenic mice, no reductions in serum HBsAg were observed with REP 2139 with up to 12 weeks of treatment. In conclusion, the antiviral effects of NAPs in DHBV infected ducks and patients with chronic HBV infection were weak or absent in woodchuck and mouse models despite similar liver accumulation of NAPs in all these species, suggesting that the mechanisms of SVP assembly and or secretion present in rodent models differs from that in DHBV and chronic HBV infections.

Background and aims: Peripartum transmission of hepatitis B virus (HBV) from an infected mother to the child can be prevented in most but not all cases by immediate vaccination of the newborn. The aim of this study was to compare the efficacy of two licensed hepatitis B vaccines, Engerix-B versus Sci-B-Vac, in preventing peripartum HBV transmission. Methods: A prospective multicenter randomized controlled study in 4 delivery centers was performed from 2009 to 2014. HBsAg positive pregnant women and their newborns were recruited at the delivery rooms. All newborns received Hepatitis B Immune Globulin within 10 h after birth, as well as active HBV vaccination at 0, 1 and 6 months of age. Maternal assessment at delivery included transaminases, blood count, international normalized ratio and viral status. Infants were tested for HBsAg, anti-HBc and anti-HBs at 12 months of age. Results: In the intention to treat (ITT), 171 infant and mother pairs fulfilled the study enrollment criteria and completed follow up, 82 received Engerix-B and 89 Sci-B-Vac. Maternal parameters and viral status were similar in both groups. At 12 months of age, the Sci-B-Vac group had lower HBsAg carriage rates (1/89, 1.1%) than the Engerix-B group (5/82, 6.1%) with borderline significance (risk difference of −0.05, 95% CI −0.11–0.007, t-test = 0.05), and borderline significance lower vaccine failure rates with anti-HBs < 10 mIU/mL in the Sci-B-Vac (2/89, 2.2%) than in the Engerix-B (8/82, 9.8%, p = 0.05). Higher seroprotection rates were found in the Sci-B-Vac group with all anti-HBs titer stratifications of >10 mIU/mL (p = 0.05), >100 mIU/mL (p = 0.05) and >1000 mIU/mL (p = 0.01). Active/passive vaccination was effective in 10/13 cases with maternal HBV DNA levels > 7 log10 IU/mL up to 9.5 log10 IU/mL, but failed in 3 cases for unknown reasons. Conclusion: Sci-B-Vac was superior to Engerix-B in preventing peripartum HBV transmission in neonates from HBsAg+ mothers and induces significantly higher anti-HBs levels. NIH registration number: NCT 01133184.

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