Search

Background In a phase 1/2 study, a maternal respiratory syncytial virus vaccine candidate (RSVPreF3) demonstrated an acceptable safety profile and efficiently increased RSV-specific humoral immune responses in non-pregnant women. Methods In this phase 2 observer-blind, placebo-controlled, randomized clinical trial (NCT04126213), the safety of RSVPreF3 (60 or 120 µg), administered during late second or third trimester, was evaluated in 213 18- to 40-year-old healthy pregnant women through 6 months postdelivery and their offspring through infancy; immunogenicity was evaluated through day 43 postdelivery and day 181 postbirth, respectively. Results RSVPreF3 was well tolerated. No pregnancy-related or neonatal adverse events of special interest were considered vaccine/placebo related. In the 60 and 120 µg RSVPreF3 groups: (1) neutralizing antibody (nAb) titers in mothers increased 12.7- and 14.9-fold against RSV-A and 10.6- and 13.2-fold against RSV-B, respectively, 1 month postvaccination and remained 8.9–10.0-fold over prevaccination at day 43 postdelivery; (2) nAb titers were consistently higher compared to placebo recipients; (3) placental transfer ratios for anti-RSVPreF3 antibodies at birth were 1.62 and 1.90, respectively, and (4) nAb levels in infants were highest at birth and declined through day 181 postbirth. Conclusions RSVPreF3 maternal vaccination had an acceptable safety risk profile and induced robust RSV-specific immune responses with successful antibody transfer to their newborns. Clinical Trials Registration NCT04126213. [ABSTRACT FROM AUTHOR]

Background: Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae-specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing receptors in pneumonia.Methods: The expression of α4β7, L-selectin, and cutaneous lymphocyte antigen (CLA) on S. pneumoniae-specific plasmablasts was examined in patients with pneumonia (n = 16) and healthy volunteers given pneumococcal polysaccharide vaccine (PPV; n = 14) or pneumococcal conjugate vaccine (PCV; n = 11).Results: In patients with pneumonia, the proportion of S. pneumoniae-specific plasmablasts expressing L-selectin was high, the proportion expressing α4β7 was moderate, and the proportion expressing CLA was low. The homing receptor α4β7 was expressed more frequently in the pneumonia group than in the PPV (P = .000) and PCV (P = .029) groups, L-selectin was expressed more frequently in the PPV group than in the PCV group (P = .014); and CLA was expressed more frequently in the pneumonia group than in the PPV group (P = .001).Conclusions: The homing receptor profile in patients with pneumonia was unique yet it was closer to that in PCV recipients than in PPV recipients. These data suggest greater mucosal localization for immune response in natural infection, which is clinically interesting, especially considering the shortcomings of vaccines in protecting against noninvasive pneumonia. [ABSTRACT FROM AUTHOR]

Enteric infections induce a response of circulating pathogen-specific antibody-secreting cells (ASC). The expression of homing receptors (HRs) on these cells was studied in patients with diarrhea caused by Vibrio cholerae in Bangladesh, an area in which cholera is endemic. The gut HR, α4β7, was expressed by ∼80% of the ASC, indicating mucosal homing of these cells. However, the peripheral lymph node HR, L-selectin, was also expressed by ∼80% of the ASC specific to either cholera toxin or O antigen. In earlier findings after oral immunization in nonendemic areas, α4β7 has been expressed by ∼100% and L-selectin by ∼50% of the ASC. In comparison, the present data speak for a more systemic targeting of the immune response associated with long-lasting immunity in an endemic area. The results thus provide insight for the continued development and evaluation of vaccines. [ABSTRACT FROM PUBLISHER]

Mucosal immune mechanisms are believed to be important in host defense against urinary tract infection. To study the human immune response in the urinary tract, peripheral blood antibody-secreting cells (ASC), believed to originate from the mucosal surfaces, were investigated with the enzyme-linked immunospot assay. Pathogen-specific ASC were found in 17 (89%) of 19 patients with pyelonephritis and in 12 (70%) of 17 with LUTI (lower urinary tract infection); for infections caused by Escherichia coli, the respective figures were 17 (100%) and 10 (71%). The responses in pyelonephritis were stronger (P < .001) and lasted longer than those in LUTI: 15 patients with pyelonephritis (74%) but only 1 with LUTI (6%) had > 100 ASC/106 cells. A similar difference was seen in the number of all immunoglobulin-secreting cells. The ASC assay offers a new means for assessing the human immune response in urinary tract infection and may be useful in localizing the infection. It might prove valuable in predicting harmful postinfection processes. [ABSTRACT FROM PUBLISHER]

The development and persistence of Salmonella-specific serum antibodies ofdifferent immunoglobulin classes and subclasses were compared between those who developed reactive arthritis (n = 39) and those who did not (n = 58) after Salmonella infection. Antibodies against lipopolysaccharide and SDS-extract antigen were measured by ELISA. A significant difference was seen between the two patient groups after 4–14 months of follow-up; those with reactive arthritis had higher levels of Salmonella-specific IgM, IgG, and IgA class antibodies than those without arthritis. In the increased antibody response, secretory IgA, IgA 1, and IgG2 classes were especially well represented. The persisting antibody response is a common feature in reactive arthritis and supports persistence of the pathogen or its components in the host. The differences observed in antibody profiles between Salmonella- and Yersinia-triggered reactive arthritides suggest certain dissimilarities (e.g., in the location of persisting microbes) in the arthritogenic process due to these two microbes. [ABSTRACT FROM PUBLISHER]