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BackgroundSARS-CoV-2 mRNA vaccines have demonstrated high immunogenicity in healthy subjects and preliminary results for people living with HIV (PLWHIV) are promising too. We have previously reported the persistence of spike-specific circulating IgG and memory B cells in healthy adults up to six months after mRNA SARS-CoV-2 vaccination. Unfortunately, limited longitudinal data are available for PLWHIV and no evidence of persistent spike-specific B cells have been reported yet.MethodsWe investigated the humoral response and the persistence of spike-specific memory B cells up to six months after vaccination with two doses of mRNA vaccines in 84 PLWHIV under ART and compared them to healthy controls (HCs). Humoral response was analyzed with enzyme-linked immunosorbent assay and with an angiotensin-converting enzyme 2 (ACE2) and receptor binding domain (RBD) inhibition assay. PBMCs were analyzed with a cytofluorimetric approach for B cell phenotyping.FindingsSpike-specific IgG peaked 1 month after second dose and persisted up to six months after vaccination with no significant differences compared to HCs. The stratification of patients according to CD4+ T cell count showed a significantly lower IgG response in case of CD4InterpretationIn conclusion, the majority of PLWHIV developed spike-specific humoral and B cell responses that persist for at least six months after SARS-CoV-2 mRNA vaccination. However, hints of HIV-dependent immune impairment were revealed by altered spike-specific B cell phenotypes and by reduced spike-specific humoral response in patients with low CD4+ T cell count (

The unprecedented increase of life expectancy challenges society to protect the elderly from morbidity and mortality making vaccination a crucial mean to safeguard this population. Indeed, infectious diseases, such as influenza and pneumonia, are among the top killers of elderly people in the world. Elderly individuals are more prone to severe infections and less responsive to vaccination prevention, due to immunosenescence combined with the progressive increase of a proinflammatory status characteristic of the aging process (inflammaging). These factors are responsible for most age-related diseases and correlate with poor response to vaccination. Therefore, it is of utmost interest to deepen the knowledge regarding the role of inflammaging in vaccination responsiveness to support the development of effective vaccination strategies designed for elderly. In this review we analyse the impact of age-associated factors such as inflammaging, immunosenescence and immunobiography on immune response to vaccination in the elderly, and we consider systems biology approaches as a mean for integrating a multitude of data in order to rationally design vaccination approaches specifically tailored for the elderly.

A clear vision for vaccines research and development (R&D) is needed if Europe is to continue to lead the discovery of next generation vaccines. Innovation Partnership for a Roadmap on Vaccines in Europe (IPROVE) is a collaboration between leading vaccine experts to develop a roadmap setting out how Europe can best invest in the science and technology essential for vaccines innovation. This FP7 project, started in December 2013, brought together more than 130 key public and private stakeholders from academia, public health institutes, regulators, industry and small and medium-sized enterprises to determine and prioritise the gaps and challenges to be addressed to bolster innovation in vaccines and vaccination in Europe. The IPROVE consultation process was structured around seven themes: vaccine R&D, manufacturing and quality control, infrastructure, therapeutic vaccines, needs of small and medium-sized enterprises, vaccines acceptance and training needs. More than 80 recommendations were made by the consultation groups, mainly focused on the need for a multidisciplinary research approach to stimulate innovation, accelerated translation of scientific knowledge into technological innovation, and fostering of real collaboration within the European vaccine ecosystem. The consultation also reinforced the fact that vaccines are only as good as their vaccine implementation programmes, and that more must be done to understand and address vaccination hesitancy of both the general public and healthcare professionals. Bringing together a wide range of stakeholders to work on the IPROVE roadmap has increased mutual understanding of their different perspectives, needs and priorities. IPROVE is a first attempt to develop such a comprehensive view of the vaccine sector. This prioritisation effort, aims to help policy-makers and funders identify those vaccine-related areas and technologies where key investment is needed for short and medium-long term success.

The rVSV-ZEBOV vaccine is currently the only Ebola vaccine with demonstrated clinical efficacy in a ring-vaccination clinical trial. It has been shown to be reactogenic but immunogenic and safe in several Phase I clinical studies. However, its mechanisms of protection are unknown and available immunogenicity data are mostly limited to classical serological analysis; it is now of paramount importance to apply cutting-edge technologies, including transcriptomic and metabolomic analyses, and to perform integrative analyses with standard serology and clinical data to comprehensively profile the rVSV-ZEBOV immune signature.

Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM197, composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM197, is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM197. The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM197 was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM197 and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM197 as a promising candidate vaccine against Salmonella Typhi.

Generation of primed T cells is crucial for the development of optimal vaccination strategies. Using a TCR-transgenic CD4(+) and CD8(+) T cell adoptive transfer model, we demonstrate that a single nasal immunization with recombinant Streptococcus gordonii induces antigen-specific primed T cells in lymph nodes draining the genital and intestinal tracts with about 80% of CD4(+) and 50% of CD8(+) proliferating cells. T cell clonal expansion was also observed in cervical lymph nodes, draining the immunization site, and in the spleen. The modulation of CD44 and CD45RB marker expression indicated that proliferating T cells were activated. Proliferation in distal mesenteric and iliac lymph nodes and in the spleen was observed 5 days after nasal immunization, while in draining cervical lymph nodes proliferation peaked already at day 3. The division profile of transgenic T cells observed in iliac and mesenteric lymph nodes was discontinuous, showing the lack of early cell divisions. The kinetics of T cell clonal expansion, the discontinuous division profile and the modulation of migration markers such as CD62L suggest that activated antigen-specific T cells disseminate from the immunization site to distal intestinal and genital tracts. These data demonstrate the efficacy of nasal immunization with recombinant S. gordonii in eliciting CD4(+) and CD8(+) T cell priming not only in draining sites, but also in the genital and intestinal tracts and in the spleen.

The study of the initiation and regulation of T-cell responses to vaccine antigens is of primary importance in the rational design of mucosal adjuvants. The detection in vivo of T-cell priming following immunization can be performed by using the adoptive transfer model of naïve antigen-specific transgenic T cells into immunocompetent mice. In this work, we discuss the applications of this system for detecting in vivo the primary antigen-specific clonal expansion, the phenotype, and the effector function of transgenic T cells following mucosal immunization. OVA and the mucosal adjuvant CTB were used as a model vaccine formulation and administered by the nasal route to study T-cell priming. T helper and T cytotoxic primary proliferation and expression of activation and migration markers was observed both in draining and distal sites. This method proved to be a powerful tool to study the efficacy of mucosal adjuvants in enhancing T-cell priming.

Protein L, an immunoglobulin-binding protein of some strains of the anaerobic bacterium Peptostreptococcus magnus, has been hypothesized to be a virulence determinant in bacterial vaginosis. In order to investigate the role of protein L in peptostreptococcal virulence, the Ig-binding domains of protein L were expressed at the surface of the human oral commensal Streptococcus gordonii. Recombinant streptococci were used in vaginal colonization experiments, and protein L-expressing S. gordonii demonstrated enhanced ability to colonize the vaginal mucosa. Compared to the control strain, they also persisted for a longer period in the murine vagina.

Tetanus toxin fragment C (TTFC) was expressed on the surface of the vaccine vector Streptococcus gordonii, a Gram-positive commensal bacterium of the human oral cavity. The immunogenicity of recombinant S. gordonii expressing TTFC was assayed in mice immunized by the parenteral and mucosal routes. High serum TTFC-specific IgG responses were induced in both BALB/c and C57BL/6 mice immunized subcutaneously. A total of 82% of vaccinated BALB/c mice were protected from the lethal challenge with 50 LD(50) of tetanus toxin (TT) and a direct correlation between the serum TTFC-specific IgG concentration and survival time of unprotected animals was observed. Intranasal immunization of BALB/c mice was also effective in inducing TTFC-specific serum IgG and local IgA in lung washes. Furthermore, 38% of animals immunized intranasally were protected from the lethal challenge with 10 LD(50) of TT while all control animals died within 24 h. Analysis of the serum IgG subclasses showed that the IgG1 subclass was predominant after parenteral immunization in BALB/c mice (IgG1/IgG2a ratio congruent with6) while following mucosal immunization a mixed IgG1 and IgG2a pattern (IgG1/IgG2a ratio congruent with1) was observed. These data show that TTFC expressed on the surface of S. gordonii is immunogenic by the subcutaneous and mucosal routes and the immune response induced is capable of conferring protection from the lethal challenge with TT.

In vivo NMR techniques and substrates selectively enriched with 13 C were used to follow the step-by-step metabolism of glucose and xylose, on their own or as mixed substrates in the ratio as they occur in hydrolysates from hemicellulose. The organism used was a newly isolated strain of Klebsiella planticola isolated from soil where maize has been cultivated for 30 years. Results suggest that glucose is converted to pyruvate via the Embden-Meyerhof pathway and then to lactate and ethanol. No evidence of 2,3-butandiol or formate metabolism was observed. This organism had a higher rate of uptake of xylose than previously studied microorganisms, resulting in ethanol, lactate, acetate succinate and formate as end products. Xylose metabolism in K. planticola G11, unlike that reported for many other organisms, was not inhibited by glucose. The addition of glucose, after 2 h of xylose fermentation, did not change the rate of xylose metabolism.

Non-pathogenic Gram-positive oral commensal bacteria expressing recombinant fusion proteins on their cell surface have been successfully used to raise both a mucosal and a systemic immune response to foreign antigens while colonizing the oropharynx. In this system, fusion-protein vaccines are delivered and anchored to the surface of a commensal, which occupies the mucosal niche invaded by a particular pathogen. Surface expression of these foreign proteins is achieved by exploiting the common mechanism employed by Gram-positive bacteria for translocating and anchoring proteins to the cell surface. The process offers a safe alternative to the use of engineered pathogens as live vaccine delivery vehicles.