Live Viral Vaccines in Immunocompromised Patients

Arnaud G L'Huillier; Klara M Posfay-Barbe


Future Virology. 2014;9(2):161-171. 

In This Article

Varicella-zoster Virus Vaccine

Disseminated varicella–zoster virus (VZV) infection is a rare but feared life-threatening complication of VZV infection. In SOT recipients, VZV infection is associated with a high mortality rate.[22] Severe complications of VZV disease usually trigger a prudent approach in immunocompromised hosts with early intravenous treatment when VZV infection is apparent, but also pre-emptive treatment with antivirals with or without intravenous specific immunoglobulins in case of exposure.[23] The widespread use of antiviral prophylaxis could potentially be curtailed if VZV vaccination is more widely performed in immunocompromised patients.

VZV vaccine was developed in the 1970s by Michiaki Takahashi using the Oka strain, but US licensure was only obtained in 1995. Since then, its efficacy to decrease varicella-related hospitalizations in patients >1 year of age has been recognized.[24] In 2006, the US FDA also authorized a live attenuated Oka virus vaccine against (zoster) shingles, which is 14 times more concentrated than the VZV vaccine. This vaccine is currently recommended to previously immune seniors, and aims to reduce the incidence of zoster and the post-herpetic neuralgia.[25] Neutralizing antibodies used as surrogate markers for immunity do not necessarily correlate with protection from infection, as CMI, which is rarely measured in studies, plays a major role in protection.[26,27] Large studies concerning the VZV vaccine's efficacy in transplant recipients are lacking and VZV vaccine is currently not recommended after SOT by most experts, but encouraged before transplantation when possible and when the transplant candidate is seronegative.[12,28] Seroprotection following vaccination, when vaccinated before transplantation, is present in a significant proportion of patients, with no severe side effects.[29] A number of smaller studies have reported their experience in vaccinating transplant recipients after SOT ( Table 1 ). Most of these studies were performed in pediatric liver transplant recipients, usually at least 6 months after transplantation, with low dose immunosuppression and stable organ function. Seroconversion rates were between 65 and 100%, with moderately waning titers (i.e., persisting for >2 years) on follow-up when available. Side effects were similar to the healthy population and breakthrough disease was rarely reported.[30] In a cohort of 36 pediatric liver transplant recipients vaccinated at our institution, measures of specific CMI (IFN-γ production by VZV-specific CD4+ T cells) also increased significantly after VZV vaccination.[31]

In cancer patients, VZV vaccination was demonstrated as safe and efficient (98% seroconversion rate after 1–2 doses) in children with leukemia in remission, with low rates of side effects.[37] When vaccinated against VZV at the time of diagnosis, seroconversion is also high, but published sample sizes are small. Household members of patients with cancer can be safely vaccinated with VZV vaccine. This can be recommended because vaccine virus cannot be isolated from oropharyngeal secretions of vaccinated individuals.

In HSCT recipients, seronegative patients should preferably be vaccinated before transplantation.[14] No data exist on the ideal timing between vaccination and start of conditioning. After HSCT, recommendations suggest immunizing at least 24 months later with relatively good results (i.e., low adverse events and high seroconversion rate), but some centers showed efficient vaccination 3–4 months after HSCT.[38,39] In one study, there was no significant difference in response between recipients of a matched related or alternative donor graft or between those given a T cell-depleted or T-replete alternative donor graft.[38]

Patients with congenital immune deficiencies have different responses to live-attenuated viral vaccines. VZV vaccine can be administered safely to patients with chronic granulomatous diseases and also to patients with early or late complement defect disorders, but in the case of patients with significant B-cell deficiencies, phagocytic or cytokine generation disorders, or severe combined immunodeficiencies specialized advice should be sought before giving VZV vaccine.

Avidity reflects the strength of the interaction between specific antibodies and antigens, and increases over time. In HIV+ children, our group showed that the children had an impaired antibody memory to VZV with lower antibody levels, but also lower avidity than healthy children.[40] Others also acknowledged that HIV+ patients do not maintain protective antibody titers.[41] Therefore, VZV vaccination could represent an interesting option in these patients. Levin et al. showed that HIV+ children with a CD4+ T-cell percentage of at least 15% and a CD4+ T-cell count of at least 200 cells/μl are likely to benefit from receiving varicella vaccine with seroresponse rates of 83% a year after vaccination.[42,43] Finally, Gershon et al. boosted immunity to VZV by successfully vaccinating HIV+ children with a previous history of chickenpox.[44] A similar study was also performed in adults, with more modest immunological success.[45]

Use of herpes zoster vaccination in patients with inflammatory and autoimmune diseases is still uncommon.[46,47] Small studies give encouraging results regarding safety and immunogenicity, but larger, more homogenous studies are needed.

The risk of transmission of vaccine virus from a vaccinated person (e.g., a household member) to a susceptible contact, such as an immunocompromised host, appears to be very low.