IGHV1-69 B cell chronic lymphocytic leukemia antibodies cross-react with HIV-1 and hepatitis C virus antigens as well as intestinal commensal bacteria.

B-cell chronic lymphocytic leukemia (B-CLL) patients expressing unmutated immunoglobulin heavy variable regions (IGHVs) use the IGHV1-69 B cell receptor (BCR) in 25% of cases. Since HIV-1 envelope gp41 antibodies also frequently use IGHV1-69 gene segments, we hypothesized that IGHV1-69 B-CLL precursors may contribute to the gp41 B cell response during HIV-1 infection. To test this hypothesis, we rescued 5 IGHV1-69 unmutated antibodies as heterohybridoma IgM paraproteins and as recombinant IgG1 antibodies from B-CLL patients, determined their antigenic specificities and analyzed BCR sequences. IGHV1-69 B-CLL antibodies were enriched for reactivity with HIV-1 envelope gp41, influenza, hepatitis C virus E2 protein and intestinal commensal bacteria. These IGHV1-69 B-CLL antibodies preferentially used IGHD3 and IGHJ6 gene segments and had long heavy chain complementary determining region 3s (HCDR3s) (≥21 aa). IGHV1-69 B-CLL BCRs exhibited a phenylalanine at position 54 (F54) of the HCDR2 as do rare HIV-1 gp41 and influenza hemagglutinin stem neutralizing antibodies, while IGHV1-69 gp41 antibodies induced by HIV-1 infection predominantly used leucine (L54) allelic variants. These results demonstrate that the B-CLL cell population is an expansion of members of the innate polyreactive B cell repertoire with reactivity to a number of infectious agent antigens including intestinal commensal bacteria. The B-CLL IGHV1-69 B cell usage of F54 allelic variants strongly suggests that IGHV1-69 B-CLL gp41 antibodies derive from a restricted B cell pool that also produces rare HIV-1 gp41 and influenza hemagglutinin stem antibodies

The Efficacy of Flogofilm® in the Treatment of Chronic Bacterial Prostatitis as an Adjuvant to Antibiotic Therapy: A Randomized Prospective Trial

Introduction: Bacterial prostatitis (BP) is a common prostatic infection characterized by a bimodal distribution in young and older men, with a prevalence between 5-10% among all cases of prostatitis and a high impact on quality of life. Although the management of bacterial prostatitis involves the use of appropriate spectrum antibiotics, which represent the first choice of treatment, a multimodal approach encompassing antibiotics and nutraceutical products in order to improve the efficacy of chosen antimicrobial regimen is often required. Objective: To evaluate the efficacy of Flogofilm® in association with fluoroquinolones in patients with chronic bacterial prostatitis (CBP). Methods: Patients diagnosed with prostatitis (positivity to Meares-Stamey Test and symptoms duration > 3 months) at the University of Naples "Federico II", Italy, from July 2021 to December 2021, were included in this study. All patients underwent bacterial cultures and trans-rectal ultrasounds. Patients were randomized into two groups (A and B) receiving antibiotic alone or an association of antibiotics plus Flogofilm® tablets containing Flogomicina® for one month, respectively. The NIH-CPSI and IPSS questionnaires were administered at baseline, four weeks, twelve and twenty-four weeks. Results: A total of 96 (Group A = 47, Group B = 49) patients concluded the study protocol. The mean age was comparable, with a mean age of 34.62 ± 9.04 years for Group A and 35.29 ± 10.32 years for Group B (p = 0.755), and IPSS at the baseline was 8.28 ± 6.33 and 9.88 ± 6.89 (p = 0.256), respectively, while NIH-CPSI at baseline was 21.70 ± 4.38 and 21.67 ± 6.06 (p = 0.959), respectively. At 1, 3 and 6 months, the IPSS score was 6.45 ± 4.8 versus 4.31 ± 4.35 (p = 0.020), 5.32 ± 4.63 versus 3.20 ± 3.05 (p = 0.042) and 4.91 ± 4.47 versus 2.63 ± 3.28 (p = 0.005) for Groups A and B, respectively. Similarly, the NIH-CPSI total score at 1, 3 and 6 months was 16.15 ± 3.31 versus 13.10 ± 5.03 (p < 0.0001), 13.47 ± 3.07 versus 9.65 ± 4.23 (p < 0.0001) and 9.83 ± 2.53 versus 5.51 ± 2.84 (p < 0.0001), respectively. Conclusions: Flogofilm®, associated with fluoroquinolones, demonstrate a significant improvement in pain, urinary symptoms and quality of life in patients affected by chronic bacterial prostatitis in both IPSS and NIH-CPSI scores compared with fluoroquinolones alone

HIV-1 envelope gp41 antibodies can originate from terminal ileum B cells that share cross-reactivity with commensal bacteria.

Monoclonal antibodies derived from blood plasma cells of acute HIV-1-infected individuals are predominantly targeted to the HIV Env gp41 and cross-reactive with commensal bacteria. To understand this phenomenon, we examined anti-HIV responses in ileum B cells using recombinant antibody technology and probed their relationship to commensal bacteria. The dominant ileum B cell response was to Env gp41. Remarkably, a majority (82%) of the ileum anti-gp41 antibodies cross-reacted with commensal bacteria, and of those, 43% showed non-HIV-1 antigen polyreactivity. Pyrosequencing revealed shared HIV-1 antibody clonal lineages between ileum and blood. Mutated immunoglobulin G antibodies cross-reactive with both Env gp41 and microbiota could also be isolated from the ileum of HIV-1 uninfected individuals. Thus, the gp41 commensal bacterial antigen cross-reactive antibodies originate in the intestine, and the gp41 Env response in HIV-1 infection can be derived from a preinfection memory B cell pool triggered by commensal bacteria that cross-react with Env

A human monoclonal antibody prevents malaria infection by targeting a new site of vulnerability on the parasite

Development of a highly effective vaccine or antibodies for the prevention and ultimately elimination of malaria is urgently needed. Here we report the isolation of a number of human monoclonal antibodies directed against the Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) from several subjects immunized with an attenuated Pf whole-sporozoite (SPZ) vaccine (Sanaria PfSPZ Vaccine). Passive transfer of one of these antibodies, monoclonal antibody CIS43, conferred high-level, sterile protection in two different mouse models of malaria infection. The affinity and stoichiometry of CIS43 binding to PfCSP indicate that there are two sequential multivalent binding events encompassing the repeat domain. The first binding event is to a unique 'junctional' epitope positioned between the N terminus and the central repeat domain of PfCSP. Moreover, CIS43 prevented proteolytic cleavage of PfCSP on PfSPZ. Analysis of crystal structures of the CIS43 antigen-binding fragment in complex with the junctional epitope determined the molecular interactions of binding, revealed the epitope's conformational flexibility and defined Asn-Pro-Asn (NPN) as the structural repeat motif. The demonstration that CIS43 is highly effective for passive prevention of malaria has potential application for use in travelers, military personnel and elimination campaigns and identifies a new and conserved site of vulnerability on PfCSP for next-generation rational vaccine design