Essen, Germany—For a time after HSCT, patients are at risk because impaired antiviral T-cell function affects the control of herpes viruses.

One effect is that the varicella-zoster virus (VZV) primary infection and reactivation can lead to neurological manifestations such as perivascular demyelination of the central nervous system and encephalitis, hemorrhagic and necrotic skin changes, bacterial superinfections, dissemination of infection, interstitial pneumonia, and other severe organ manifestations, according to a recent study in Vaccines.

In fact, after allogeneic HSCT 41% developed VZV reactivation at a median of 227 days post-transplantation, according to German authors from University Hospital Essen. About 12% of VZV reactivations occurred in the first 100 days and 88% within the first 24 months. A total of 45% showed disseminated disease, a condition that is lethal in 10% of cases, the authors indicated while citing past research.

That is why the study team sought to determine if vaccination with the adjuvanted RZV, marketed as Shingrix, would make a significant difference by preventing infection and reactivation.

For the study, allogeneic HSCT participants—34 females and 45 males—were vaccinated with Shingrix, which contains the VZV glycoprotein E (gE). Researchers analyzed cellular immunity against various VZV antigens by interferon-gamma enzyme-linked immunosorbent spot (ELISpot).

Results indicated that peripheral blood mononuclear cells of recipients with VZV prior shingles—36 and 43, respectively—showed about twofold-higher VZV-specific responses prior to and postvaccination.

"After the first and second vaccination, ELISpot responses towards the glycoprotein E were significantly higher in males versus females (median of spots increment 18 versus 1 and 17 versus 4, respectively, P < 0.02 each)," the authors wrote. "Multivariate analysis showed that shingles and sex both impact significantly on VZV immunity."

While vaccination-induced changes could hardly be detected after stimulation with a whole VZV antigen, a significant increase in responses towards glycoprotein E was demonstrated after vaccination.

"These data indicate that vaccination with Shingrix augmented cellular, VZV-specific immunity in HSCT recipients," the researchers pointed out. "Shingles and male sex could both be identified as factors leading to increased immunity."

The authors addressed the sex difference, writing, "Whereas the influence of prior shingles was expected at first glance, the influence of sex is less clear. VZV reactivation leads to an in vivo expansion of VZV-specific T cells, which may be further 'boostered' after vaccination. Previous literature indicated that immune responses in females and males may differ, for example, the concentration of cytokines or vaccine antibodies. In females, cytomegalovirus pp65–specific IL-21 ELISpot responses were higher or antibody titers after vaccination against hepatitis B or SARS-CoV-2 virus were increased. It thus appears possible that also VZV-specific immunity shows a sex dependency."

They concluded that while vaccination with Shingrix (which contains the VZV gE) led to a significant increase in cellular in vitro responses towards VZV gE in allogenic HSCT recipients, cellular responses were weaker compared with the controls. "The current data indicate that patients with prior shingles and males exhibit higher VZV-specific IFN-γ responses. It needs to be clarified whether the higher ELISpot responses correlate with better protection against VZV infection and reactivation."

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