BackgroundImmunogenicity of cancer vaccines is impacted by adjuvants and schedule, but systematic assessments of their effects have not been performed. Montanide ISA-51, an incomplete Freund’s adjuvant (IFA), is used in many vaccine trials, but concerns have been raised about negative effects in murine studies. We found in humans that IFA enhances systemic immune responses and that repeat vaccination at one site (same site vaccination (SSV)) creates tertiary lymphoid structures (TLS) in the vaccine site microenvironment (VSME). We hypothesized that vaccination with peptides+IFA+pICLC or SSV×3 with peptides in IFA would create an immunogenic milieu locally at the VSME, with activated dendritic cells (DC), TLS-associated chemokines and a Th1-dominant VSME.MethodsBiopsies of the VSME were obtained from participants on two clinical trials who were immunized with multiple melanoma peptides (MELITAC 12.1) in adjuvants comprising IFA and/or the TLR3-agonist pICLC. Biopsies were obtained either a week after one vaccine or a week after SSV×3. Controls included normal skin and skin injected with IFA without peptides. Gene expression analysis was performed by RNAseq.ResultsVSME samples were evaluated from 27 patients. One vaccine with peptides in pICLC+IFA enhanced expression of CD80, CD83, CD86 (p<0.01), CD40 and CD40L (p<0.0001) over normal skin; these effects were significantly enhanced for SSV with peptides+IFA. Vaccines containing pICLC increased expression of TBX21 (T-bet) but did not decrease GATA3 over normal skin, whereas SSV with peptides in IFA dramatically enhanced TBX21 and decreased GATA3, with high expression of IFNγ and STAT1. SSV with peptides in IFA also reduced arginase-1 (ARG1) expression and enhanced expression of TLR adapter molecules TICAM-1 (TRIF) and MYD88. Furthermore, SSV with IFA and peptides also enhanced expression of chemokines associated with TLS formation.ConclusionsThese findings suggest that SSV with peptides in IFA enhances CD40L expression by CD4 T cells, supports a Th1 microenvironment, with accumulation of activated and mature DC. Increased expression of TLR adaptor proteins after SSV with peptides in IFA might implicate effects of the skin microbiome. Reduced ARG1 may reflect diminished suppressive myeloid activity in the VSME.Trial registration number(NCT00705640,NCT01585350).

Galactose-α-1,3-galactose (α-gal) is an oligosaccharide expressed on glycoproteins and glycolipids of nonprimate mammals and is the causal epitope of an IgE-mediated allergy to mammalian meat. 1,2 First reported in 2009, the α-gal syndrome is an increasingly appreciated problem across the southeastern United States and other parts of the world. 2 It is clear that tick bites, specifically relating to Amblyomma americanum (lone star tick), are causal in many, if not most, cases of α-gal sensitization in the United States. 3 Following sensitization, many individuals will experience allergic symptoms on ingestion of meat or other products (eg, dairy) derived from nonprimate mammals. In contrast to typical IgE-mediated reactions, which occur within minutes of exposure, the α-gal allergy typically has a delayed onset of 2 to 6 hours. 2 The severity of the reaction varies from general urticaria to anaphylaxis, and individuals may not react to every exposure. Because of these atypical features, proper diagnosis can prove challenging. An epidemiological investigation of a pediatric population reported that α-gal may be misdiagnosed as recurrent urticaria or idiopathic anaphylaxis. 4 While a recent report postulated that α-gal syndrome might represent a novel cause of chronic urticaria, further research failed to find such an association. 5,6 Nevertheless, in areas where α-gal sensitization is prevalent, the potential for misdiagnosing cases of α-gal syndrome as chronic urticaria still exists. Here, we report cases labeled as chronic urticaria or chronic idiopathic urticaria within a cohort of patients in central Virginia being evaluated for α-gal syndrome.

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clinical manifestations of early secondary syphilis include small papular, follicular, vesicular, corymbiform, psoriasiform rashes, while late secondary syphilis presents as nodular, annular, pustular, frambesiform, nodular-ulcerative form. 1,2 Annular secondary syphilis is mainly located at the mucocutaneous junction of the nasal alae and the oral commissure with the prevalence of 5.7-13.6%. 1 Therefore, the syphilitic lesion in our case is rare.The first line of treatment is the intramuscular injection of 2.4 million units of benzathine benzylpenicillin. Other treatments such as doxycycline can be prescribed. 3 Differential diagnosis of penile annular lesion includes annular lichen planus, annular psoriasis, granuloma annulare, and dermatophyte infection. 1 Histologically, typical secondary syphilis shows lichenoid psoriasiform dermatitis with lymphoplasma cell infiltration. However, the pathology can be variable or nonspecific. 4 Based on a previous history of homosexual contact, annular lesion on the penis, serological tests, and a good response to benzathine penicillin G treatment confirmed the diagnosis of penile annular secondary syphilis.In conclusion, annular syphilitic lesion on the penis is a rare manifestation of secondary syphilis at an unusual location, which can be misdiagnosed with other annular skin lesions.Therefore, we should recognize annular secondary syphilis in order to treat and prevent consequences of syphilis.

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