Challenges on Induction of Broadly Neutralizing Antibodies for Optimization of HIV Vaccines Development and Vectored Immunoprophylaxis

Despite extensive research efforts, a preventive human immunodeficiency virus (HIV) vaccine remains one of the major challenges in the field of AIDS research. Experimental strategies which have been proven successful for other viral vaccines are not enough to tackle HIV-1 and new approaches to design effective preventive AIDS vaccines are of utmost importance. Due to enormous diversity among global circulating HIV strains, an effective HIV vaccine must elicit broadly protective antibodies based responses;therefore discovering new broadly neutralizing antibodies (bNAbs) against HIV has become major focus in HIV vaccine research. However further understanding of the viral targets of such antibodies and mechanisms of action of bNAbs is required for advancement of HIV vaccine research. This technical note discusses our current knowledge on the bNAbs and immunoprophylaxis using viral vectors with their relevance in designing of new candidates to HIV-1 vaccines.

Prevention of vertical transmission of hepatitis B virus infection

Hepatitis B virus(HBV)is the leading cause of chronic viral hepatitis.Annually,almost two million children younger than 5 years acquire the infection,mostly through vertical or horizontal transmission in early life.Vertical transmission of HBV is a high efficacy phenomenon ranging,in the absence of any preventive interventions,from 70%to 90%for hepatitis e antigen positive mothers and from 10%to 40%for hepatitis e antigen-negative mothers.Maternal viraemia is a preeminent risk factor for vertical transmission of HBV.Maternal screening is the first step to prevent vertical transmission of HBV.Hepatitis B passive and active immunoprophylaxis at birth together with antiviral treatment of highly viraemic mothers are the key strategies for global elimination of HBV infection.Strategies are needed to promote implementation of birth-dose vaccination and hepatitis B immunoglobulins in low-and middle-income countries where the prevalence of the infection is at the highest.

Current evidence on the management of hepatitis B in pregnancy

Hepatitis B virus(HBV) infection is one of the main public health problems across the globe,since almost one third of the world population presents serological markers of contact with the virus. A profound impact on the epidemiology has been exerted by universal vaccination programmes in many countries,nevertheless the infection is still widespread also in its active form. In the areas of high endemicity(prevalence of hepatitis B surface antigen positivity > 7%),mother-to-child transmission represents the main modality of infection spread. That makes the correct management of HBV in pregnancy a matter of utmost importance. Furthermore,the infection in pregnancy needs to be carefully assessed and handled not only with respect to the risk of vertical transmission but also with respect to gravid women health. Each therapeutic or preventive choice deserves to be weighed upon attentively. On many aspects evidence is scarce or controversial. This review will highlight the latest insights into the paramount steps in managing HBV in pregnancy,with particular attention to recommendations from recent guidelines and data from up-do-date research syntheses.

Preparation of Water Soluble Yeast Glucan by Four Kinds of Solubilizing Processes

(1→3)-β-D-glucan?from the inner cell wall of Saccharomyces cerevisiae is considered a member of a class of drugs known as biological response modifiers (BRM). However the glucan was an insoluble polysaccharide, which could be the major barrier to the utilization of glucan. In this case, the insoluble glucan was convent into a soluble form by four kind of solubilizing processes. The yield, solubility, chemistry structure and immunoprophylaxis efficacy of the soluble products were compared. Our date suggest that urea has a significant effect on yield, and DMSO has a significant effect on solubility. FT-IR spectra, 13C NMR spectra and helix-coil transition analysis demonstrate that the chemistry structure of native and solubilizing glucans have no significant difference. They still have the triple helical structure. The solubility and immunoprophylaxis efficacy assay indicate that the introduction of phosphate group not only enhanced the solubility of glucan, but also improved the survival rate of mice challenged with E. coli.

A Real-world Prospective Study of Mother-to-child Transmission of HBV in China Using a Mobile Health Application (Shield 01)

Background and Aims:The World Health Organization(WHO)Western Pacific Region set a target of eliminating mother-to-child transmission(MTCT)of hepatitis B virus(HBV)by 2030.To assess the feasibility of this target in China,we carried out an epidemiological study to investigate the status quo of MTCT in the real-world setting.Methods:One thousand and eight hepatitis B surface antigen-positive preg-nant women were enrolled at 10 hospitals.Immunoprophy-laxis was administered to infants.In addition,mothers with HBV DNA level>2,000,000 IU/mL were advised to initiate antiviral therapy during late pregnancy.A health application called SHIELD was used to manage the study.Results:Nine hundred and five of the enrolled mothers,with 924 infants,completed the follow-up.Birth-dose hepatitis B vaccine and hepatitis B immunoglobulin were received by 99.7%and 99.7%of infants,respectively,within 24 h after birth.There ;were 446 mothers who received antiviral therapy,including 72.3%of the mothers with HBV DNA level>2,000,000 IU/mL and 21.0%of the mothers with HBV DNA level<2,000,000 IU/mL.Eight infants were infected with HBV.The overall rate of MTCT was 0.9%.Birth defects were rare(0.5%among in-fants with maternal antiviral exposure versus 0.7%among infants without exposure;p=1.00).Conclusions:The MTCT rate was lower than the WHO Western Pacific Region elimina-tion MTCT target in this real-world study,indicating that a comprehensive management composed of immunoprophy-laxis to infants and antiviral prophylaxis to mothers may be a feasible strategy to achieve the 2030 WHO elimination goal.

Elimination of hepatitis B virus infection in children:experience and challenge in China

Chronic hepatitis B virus(HBV)infection is a serious health issue because of its severe sequelae.Prevention of mother-to-child transmission(MTCT)of HBV is critical to eliminate chronic HBV infection.Here,we reviewed the progress toward the elimination of HBV infection in children in China in the recent decade.A universal hepatitis B vaccination program started from 2002 has been intensified,with the coverage of timely birth dose>95%of all newborn infants from 2012.Since 2011,China has taken a nationwide program to administer hepatitis B immunoglobulin(HBIG)with free of charge in all neonates of HBV-infected mothers,leading to a significant increment of timely use of HBIG.The prevalence of hepatitis B surface antigen(HBsAg)was declined from around 10%among children in 1980s to<0.5%among children born after 2011.Administration of oral antiviral agents in HBV-infected pregnant women with HBV DNA>2105 U/mL during the third trimester is increasing,which will further reduce MTCT of HBV.However,there are some challenges in the elimination of HBV infection in children,which need to overcome by the concerted efforts.Nevertheless,it is anticipated that China will achieve the goal set by the World Health Organization that the prevalence of HBsAg in children aged<5 years is0.1%by 2030.

Vertical transmission of hepatitis B virus:propositions and future directions

Chronic hepatitis B virus(HBV)infection due to vertical transmission remains a critical concern with regards to eliminating HBV infection.Implementation of hepatitis B vaccine,the foundation to prevent perinatal and horizontal transmission,has reduced the prevalence of HBV by>80%.In countries where the hepatitis B immune globulin(HBIG)is available,such as China and the United States,the administration of HBIG and hepatitis B vaccine to the infants of mothers who are positive for hepatitis B surface antigen has become a standard practice and is effective in preventing vertical transmission.Accumulating evidence on the efficacy and safety of antiviral prophylaxis during pregnancy indicates the probability of attaining the goal of the World Health Organization to eliminate hepatitis by 2030.In this review,we discuss the transmission routes,diagnostic criteria,and preventive strategies for vertical transmission.A preventive program that includes screening before pregnancy,antiviral prophylaxis during pregnancy,and postpartum immunoprophylaxis provides“perfect strategies”to eliminate vertical transmission.However,there is still a notable gap between“perfect strategies”and real-world application,including insufficient coverage of timely birth dose vaccine and the efficacy and necessity of HBIG,especially in mothers who are negative for hepatitis B envelope antigen.In particular,there is a clear need for a comprehensive long-term safety profile of antiviral prophylaxis.Therefore,feasible and cost-effective preventive strategies need to be determined across regions.Access also needs to be scaled up to meet the demands for prophylaxis and prevalence targets.

CSOG MFM Committee Guideline: Management of Hepatitis B During Pregnancy and Prevention of Mother-to-Child Transmission of Hepatitis B Virus (2020)

Mother-to-child transmission (MTCT) of hepatitis B virus (HBV) is the main cause of chronic hepatitis B. The prevention of MTCT plays a critical role in control chronic hepatitis B. The main purpose of the present clinical guidelines is to aid healthcare providers in managing pregnant women with positive HBsAg and in preventing MTCT of HBV. We recommend: (1) all pregnant women require prenatal screen for hepatitis B serological markers;(2) newborn infants of mothers with negative hepatitis B surface (HBsAg) require administration of hepatitis B vaccine on a 0, 1, and 6 month-schedule;(3) newborn infants of mothers with positive HBsAg need hepatitis B immunoglobulin (HBIG) and birth dose vaccine within 12 hours (the sooner the better) after birth, followed by injection of the second and third dose of hepatitis B vaccine at the age of one and six months respectively;(4) in preterm neonates or neonates with poor health conditions born to HBsAg-positive mothers, the immunoprophylaxis measures should be appropriately taken;(5) to further reduce MTCT of HBV, pregnant women with HBV DNA levels >2×105 IU/mL or positive hepatitis B e antigen may receive oral antivirals, starting from 28 to 32 weeks of gestation and discontinuing the drug on the delivery day;(6) cesarean section is not recommended to reduce MTCT of HBV;(7) breastfeeding is recommended in infants of HBsAg-positive mothers, regardless of maternally positive hepatitis B e antigen, maternal nipple injury or bleeding, oral mucosal injury in neonates or infants;(8) breastfeeding is recommended in infants born to HBsAg-positive mothers who require continuation of antiviral therapy after delivery, and the infants should be followed up to observe whether adverse effects develop;and (9) the infants born to HBsAg-positive mothers should be tested for hepatitis B serological markers at the age of 7-12 months, and those who are negative for HBsAg and anti-HBs should receive three doses of hepatitis B vaccine on the 0, 1, and 6 month-schedule as soon as possible.