Kinetics of Hemagglutination-Inhibiting Antibodies Following Maternal Influenza Vaccination Among Mothers With and Those Without HIV Infection and Their Infants.

BACKGROUND: We evaluated the immunogenicity of trivalent inactivated influenza vaccine (IIV3) in pregnant women with and those without human immunodeficiency virus (HIV) infection and the persistence of hemagglutination-inhibiting antibodies in mothers and infants. METHODS: Antibodies were measured before vaccination, 1 month after vaccination, at delivery, and at postpartum week 24 in mothers and within 1 week of birth and at 8, 16, and 24 weeks of age in infants. RESULTS: We enrolled 98 HIV-uninfected and 100 HIV-infected pregnant women, including 93% with a CD4(+) T-cell count of ≥ 200 cells/µL. Compared with HIV-uninfected women, HIV-infected women had lower seroconversion rates (ranging from 63%-92% vs 36%-40%), lower antibody titers through postpartum week 24, and overlapping antibody half-lives (ranging from 106-121 vs 87-153 days). Infant titers were lower than the maternal titers within 1 week of delivery, regardless of vaccine strain and HIV exposure status. Compared with HIV-unexposed infants, HIV-exposed infants had a similar transplacental influenza virus antibody transfer ratio, lower titers, and a lower frequency of titers ≥ 1:40 (ranging from 82%-95% vs 43%-79%) at birth and higher antibody half-lives (ranging from 43-45 vs 56-65 days). CONCLUSIONS: Compared with HIV-uninfected pregnant women, HIV-infected pregnant women had lower antibody responses and persistence. Compared with HIV-unexposed infants, HIV-exposed infants had lower antibody levels at birth but similar antibody levels after 8 weeks of life. Early IIV3 administration during pregnancy did not decrease antibody titers among infants at birth.

Effect of abatacept on immunogenicity of vaccines in individuals with type 1 diabetes.

Abatacept delayed progression of type 1 diabetes (T1D) when administered soon after diagnosis. Its use in T1D is expanding to prevention trials and, therefore, it is important to fully characterize its immunosuppressive effect. We compared antibody responses to trivalent inactivated influenza vaccine (TIIV) administered during 2 consecutive seasons and to tetanus toxoid (TT) vaccine administered after 24 months of treatment in115 early onset T1D subjects randomly assigned to 24 months of abatacept (N=71) or placebo (N=34). Anti-influenza titers before TIIV were similar between the 2 treatment groups and both groups had significant increases after vaccination. Although the magnitude of antibody responses against some influenza serotypes was significantly lower (p<0.05) in abatacept compared with placebo recipients, no differences were observed in the proportion of subjects with protective titers against influenza after vaccination. The magnitude of antibody responses against TT also tended to be lower (p=0.06) in abatacept compared with placebo recipients, without affecting the proportion of subjects who achieved protective titers. We conclude that abatacept moderately decreases the magnitude of antibody responses to recall vaccination. Further studies are needed to assess its effect on primary immunization.

Reactivation of latent viruses in individuals receiving rituximab for new onset type 1 diabetes.

BACKGROUND: Rituximab has been successfully used as an experimental therapy in different autoimmune diseases. Recently, a double-blind placebo-controlled phase-2 study in early onset type 1 diabetes showed that rituximab delayed progression of the disease. However, like with any immunosuppressive therapy, there is a concern of opportunistic viral reactivations with the use of rituximab, including herpes and polyomaviruses. OBJECTIVES: To study the incidence of new infections and reactivations with BK, JC, Epstein-Barr and cytomegalovirus (BKV, JCV, EBV and CMV) in T1D participants in the phase-2 rituximab study. STUDY DESIGN: Subjects received 4 weekly doses of rituximab (N = 57) or placebo (N = 30) during the first month of study. Blood samples obtained at weeks 0, 12, 26, 56 and 78 were assayed for CMV, EBV, BKV and JCV by real-time DNA PCR and serology. RESULTS: EBV reactivations were diagnosed by PCR in 25% of placebo, but none of rituximab recipients (p < 0.01). There were no episodes of CMV viremia in either treatment group. BKV viremias were significantly more common in the rituximab recipients (9%) compared with placebo controls (0, p < 0.01). No JCV reactivations were detected in this study, but among 6 rituximab and 2 placebo recipients who seroconverted for JCV during the study, only one rituximab recipient had detectable viremia. All infections were asymptomatic. CONCLUSIONS: Four doses of rituximab administered to individuals with early onset T1D decreased the incidence of asymptomatic EBV reactivations, as predicted by the rituximab-mediated elimination of memory B-cells, but increased the frequency of asymptomatic viremias caused by polyomaviruses.