Remarkably Cornelius et al report for the first time

Remarkably, Cornelius et al. report for the first time HBV-neutralizing antibodies in all seven so-far tested human recipients of the BM32 vaccine, i.e., of preS antigen without other HBV antigens. Assay of neutralizing antibodies has been difficult because for long time the only HBV-susceptible cell cultures were human, ape or Tupaia hepatocyte explants which are of very limited availability. Since it is known that the preS1 attachment site binds to the sodium-dependent taurocholate cotransporting peptide (NTCP), a bile order Sulindac sulfide transporter which mediates entry of HBV (), it became possible to create NTCP-expressing hepatic cell lines susceptible for HBV which the authors have applied. The number of the vaccine recipients evaluated is small and no titers were determined, but the data are sufficient to conclude that preS antigen alone can induce HBV-neutralizing antibodies. The construct contained both preS1 and preS2. The N-terminal part of preS1 is the binding site for NTCP, and antibodies against this part were shown to neutralize HBV () while the C-terminal part is immunogenic but does not induce neutralizing antibodies. The preS2 part is nonessential for HBV and antibodies against preS2 may be dispensable, but the preS2 part may provide T helper epitopes. An important reason to focus on preS1-based hepatitis B vaccines is the fact that L protein is enriched in the HBV particle while the S and M protein are most abundant on noninfectious HBsAg particles (). These are present in 3000-fold excess and may consume the neutralizing antibodies against them. Contrary to the protective HBsAg epitopes, the preS epitopes are sequential, relatively well conserved between the HBV genotypes and have not yet been subject to escape mutations. It appears possible that the paper from Cornelius et al. may encourage the field to re-vitalize research on hepatitis B vaccines. Disclosure
The case of the “Berlin Patient” is well-known. In 2007, an HIV-infected adult with leukemia underwent allogeneic hematopoietic stem cell transplant and was cured of his cancer (). As the donor was homozygous for the CCR5Δ32 deletion (which makes CD4 T cells difficult to infect with HIV), the repopulated immune system lacked any detectable HIV and the patient has been apparently been cured. Two subsequent allogeneic transplants performed under potent ART (which protected the donor cells from de novo infection) resulted in a dramatic reduction in the frequency of cells harboring replication-competent HIV (generally referred to as the HIV “reservoir”) (). This was not enough to cure these two patients, however, as both individuals experienced a delayed but robust rebound in viremia after stopping therapy. A true cure will likely require complete eradication of the entire reservoir of HIV. This is a formidable challenge.
Yaws is caused by infection with subspecies (), a spirochete that is very closely related to subsp. (), the etiologic agent of syphilis (). Whereas syphilis is a sexually transmitted disease with a global distribution, yaws is transmitted by direct contact of broken skin with active lesions and primarily affects children who live in poor rural communities in humid, tropical areas of Africa, Southeast Asia and the Pacific Islands. Both syphilis and yaws are chronic, multi-stage diseases that can cause destructive lesions of skin, bone and cartilage. Control of these diseases is based on interrupting transmission through the identification and treatment of cases and their contacts. Because of the antigenic similarity of the () subsp., serological tests that are used for diagnosis of syphilis are also used for diagnosis of yaws, although these tests cannot differentiate the two diseases. However, molecular differentiation of the subsp. is possible via PCR amplification of polymorphic genomic loci coupled with DNA sequencing (). In 2012, the World Health Organization (WHO) launched a yaws eradication program based on mass azithromycin treatment of individuals in endemic communities followed by clinical and serological surveys to detect and treat remaining cases and their contacts (). An earlier WHO campaign conducted in the mid-20th century reduced the number of yaws cases by nearly 95%. However, yaws was not eradicated and when local efforts to prevent new cases failed, yaws resurged.