In patients rendered immunocompromised by allogeneic hematopoietic stem cell transplantation (HSCT), a single dose of the respiratory syncytial virus (RSV) vaccine within the first year afterward resulted in low seroconversion rates, as reported by Redjoul et al in JAMA Network Open. However, a second dose appeared to enhance the humoral immune response of overt nonresponders.
“Several clinical and biological factors previously associated with vaccine immunogenicity against other viruses in HSCT recipients were shared with regard to RSV,” the investigators added.
Study Details
The cohort included 92 patients who underwent allogeneic HSCT—64 and 20 for myeloid and lymphoid neoplasms (all but 3 in remission), respectively, and 8 for nonmalignant diseases—all sharing risk factors for severe RSV infection, and all of whom received a bivalent prefusion F (pre-F) RSV vaccine. A total of 66% of the population was male, and the median patient age at vaccination was 63 years (interquartile range [IQR] = 53–70 years).
Vaccine immunogenicity was determined via the quantification of serum anti–pre-F RSV immunoglobulin G (IgG) levels at the time of vaccination (baseline) and after 4 weeks, as well as at 12 weeks for 47 patients. Major endpoints were the frequency and factors associated with seroconversion, which was defined as a fourfold increase in antibody titers from baseline to 4 weeks after vaccination.
Seroconversion
At baseline, anti–pre-F IgG antibodies were detectable and quantifiable in 82 recipients (89%; median [IQR] = 7,582 [2,170–19,288] IU/mL), whereas 10 (11%) were negative (< 10 IU/mL). Lower baseline titers appeared to be significantly associated with a shorter interval between HSCT and vaccination, lower lymphocyte counts, and use of immunosuppressive therapy within the 3 months before vaccination. The investigators reported no serious adverse events after one or two vaccine doses.
Longer time since HSCT, absence of systemic immunosuppressive therapy, and higher lymphocyte counts were found to be significantly associated with seroconversion. Seroconversion was observed in 75% (n = 45 of 60) of patients beyond 1 year after HSCT; according to the investigators, this applied to 9% (n = 3 of 32) of those vaccinated within the first year. Nonresponding patients seemed more likely to have received intravenous immunoglobulin supplementation within the 3 months before vaccination, which the investigators noted as indicative of a greater degree of immunosuppression. Of note, they reported that these same factors were associated with seroconversion when defined by a twofold lower or eightfold higher number of anti-RSV titers. A total of 6 of the 10 recipients who demonstrated undetectable anti–pre-F IgG levels at baseline were found to have detectable anti-RSV titers 4 weeks after vaccination.
Revaccination
According to the investigators, in responding patients, antibody levels remained high over time and were significantly higher at 12 vs 4 weeks after vaccination. Patients considered nonprotected despite vaccination were administered a second dose. Three of the eight revaccinated patients exhibited an increase in anti-RSV titers after the second vaccine dose, with sustained elevation observed in the two recipients who were tested more than 4 weeks afterward.
Correlation With Neutralizing Antibodies
In a subset of 15 patients, the investigators analyzed the correlation between RSV pre-F IgG antibody titers and neutralizing antibody titers. They reported a strong association between normalized RSV pre-F IgG antibodies and neutralizing antibody titers (50% neutralizing titer).
“Limitations of the study include the absence of immunization quantification at long term after vaccination,” the investigators remarked.
They concluded: “Additional studies are needed to define a clinical protection correlate in these unfavorable immune conditions and to conduct multivariable analyses, also taking into account the putative impact of cellular responses to vaccination.”
Sébastien Maury MD, PhD, of Assistance Publique—Hôpitaux de Paris, Hôpital Henri Mondor, Créteil, France, is the corresponding author of the JAMA Network Open article.
Disclosure: The cost of vaccine doses was supported by Promex Stiftung für die Forschung. For full disclosures of the study authors, visit jamanetwork.com.
