Conventional vaccine strategies have been highly efficacious for several decades in reducing mortality and morbidity due to infectious diseases. The bane of conventional vaccines, such as those that include whole organisms or large proteins, appear to be the inclusion of unnecessary antigenic load that, not only contributes little to the protective immune response, but complicates the situation by inducing allergenic and/or reactogenic responses. Peptide vaccines are an attractive alternative strategy that relies on usage of short peptide fragments to engineer the induction of highly targeted immune responses, consequently avoiding allergenic and/or reactogenic sequences. Conversely, peptide vaccines used in isolation are often weakly immunogenic and require particulate carriers for delivery and adjuvanting. In this article, we discuss the specific advantages and considerations in targeted induction of immune responses by peptide vaccines and progresses in the development of such vaccines against various diseases. Additionally, we also discuss the development of particulate carrier strategies and the inherent challenges with regard to safety when combining such technologies with peptide vaccines.

Genital chlamydial infections lead to severe upper reproductive tract pathology in a subset of untreated women. We demonstrated previously that tumor necrosis factor (TNF)‐α‐producing CD8⁺ T cells contribute significantly to chlamydial upper genital tract pathology in female mice. In addition, we observed that minimal chlamydial oviduct pathology develops in OT‐1 transgenic (OT‐1) mice, wherein the CD8⁺ T‐cell repertoire is restricted to recognition of the ovalbumin peptide Ova_257–264, suggesting that non‐Chlamydia‐specific CD8⁺ T cells may not be responsible for chlamydial pathogenesis. In the current study, we evaluated whether antigen‐specific CD8⁺ T cells mediate chlamydial pathology. Groups of wild‐type (WT) C57BL/6J, OT‐1 mice, and OT‐1 mice replete with WT CD8⁺ T cells (1 × 10⁶ cells per mouse intravenously) were infected intravaginally with C. muridarum (5 × 10⁴ IFU/mouse). Serum total anti‐Chlamydia antibody and total splenic anti‐Chlamydia interferon (IFN)‐γ and TNF‐α responses were comparable among the three groups of animals. However, Chlamydia‐specific IFN‐γ and TNF‐α production from purified splenic CD8⁺ T cells of OT‐1 mice was minimal, whereas responses in OT‐1 mice replete with WT CD8⁺ T cells were comparable to those in WT animals. Vaginal chlamydial clearance was comparable between the three groups of mice. Importantly, the incidence and severity of oviduct and uterine horn pathology was significantly reduced in OT‐1 mice but reverted to WT levels in OT‐1 mice replete with WT CD8⁺ T cells. Collectively, these results demonstrate that Chlamydia‐specific CD8⁺ T cells contribute significantly to upper genital tract pathology.

In this straightforward study, Murthy et al . show that mice whose CD8 T cells that are ‘locked-in’ for the recognition of one antigen (OVA), do not show any de

Background. We demonstrated previously that tumor necrosis factor α (TNF-α)–producing Chlamydia-specific CD8⁺ T cells cause oviduct pathological sequelae. Methods. In the current study, we used wild-type C57BL/6J (WT) mice with a deficiency in genes encoding TNF receptor superfamily member 1a (TNFR1; TNFR1 knockout [KO] mice), TNF receptor superfamily member 1b (TNFR2; TNFR2 KO mice), and both TNFR1 and TNFR2 (TNFR1/2 double KO [DKO] mice) and mix-match adoptive transfers of CD8⁺ T cells to study chlamydial pathogenesis. Results. TNFR1 KO, TNFR2 KO, and TNFR1/2 DKO mice displayed comparable clearance of primary or secondary genital Chlamydia muridarum infection but significantly reduced oviduct pathology, compared with WT animals. The Chlamydia-specific total cellular cytokine response in splenic and draining lymph nodes and the antibody response in serum were comparable between the WT and KO animals. However, CD8⁺ T cells from TNFR2 KO mice displayed significantly reduced activation (CD11a expression and cytokine production), compared with TNFR1 KO or WT animals. Repletion of TNFR2 KO mice with WT CD8⁺ T cells but not with TNFR2 KO CD8⁺ T cells and repletion of TNFR1 KO mice with either WT or TNFR1 KO CD8⁺ T cells restored oviduct pathology to WT levels in both KO groups. Conclusions. Collectively, these results demonstrate that TNFR2-bearing CD8⁺ T cells and TNFR1-bearing non-CD8⁺ T cells contribute significantly to oviduct pathology following genital chlamydial infection.

The term lung disease describes a broad category of disorders that impair lung function. More than 35 million Americans have a preventable chronic lung disease with high mortality rates due to limited treatment efficacy. The recent increase in patients with lung disease highlights the need to increase our understanding of mechanisms driving lung inflammation. Connexins, gap junction proteins, and more specifically connexin 43 (Cx43), are abundantly expressed in the lung and are known to play a role in lung diseases. This review focuses on the role of Cx43 in pathology associated with acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD) and asthma. Additionally, we discuss the role of Cx43 in preventing disease through the transfer of mitochondria between cells. We aim to highlight the need to better understand what cell types are expressing Cx43 and how this expression influences lung disease.