During the past three decades, a gradual shift in the age of infection with hepatitis A virus (HAV) from early childhood to adulthood has been observed. There is a general lack of updated data on HAV burden of disease, incidence and age-specific seroprevalence in countries of the Middle East and North Africa (MENA) region. The aim of this article is to review the published data on anti-HAV seroprevalence, an important tool to monitor infections rates, in countries of the MENA region and associated risk factors including water and socioeconomic data when available. Data on anti-HAV seroprevalence were found for 12 of 25 MENA countries. We show that MENA countries, similar to other areas in the world, have a clear shift in HAV incidence with a decline among young age groups and an increase among adults and older individuals. This would likely be associated with increased morbidity and increased risks of outbreaks among younger age groups. Consequently, the continuous surveillance of hepatitis A cases and the inclusion of hepatitis A vaccine in the expanded immunization programmes are needed in countries of the MENA.

Induction of an antigenically broad and vigorous primary T-cell immune response by myeloid dendritic cells (DC) in blood and؉ T cells and was broadly directed to multiple regions of Gag, Env, and Nef that corresponded to known and predicted major histocompatibility complex class I epitopes. Polyfunctional CD8 ؉ T-cell responses, defined as single-cell production of more than one cytokine (IFN-␥, interleukin 2, or tumor necrosis factor alpha), chemokine (macrophage inhibitory factor 1␤), or cytotoxic degranulation marker CD107a, were primed by moDC, LC, and idDC to HIV-1 Gag and reverse transcriptase epitopes, as well as to Epstein-Barr virus and influenza A virus epitopes. Thus, three major types of blood and tissue myeloid DC targeted by HIV-1, i.e., moDC, LC, and idDC, can prime multispecific, polyfunctional CD8 ؉ T-cell responses to HIV-1 and other viral antigens.

A potentially powerful strategy for therapeutic HIV vaccination is the use of DC transfected with mRNA encoding autologous viral Ag, as epitopes presented by transfected DC would exactly reflect those expressed by infected cells in the individual. Using human and rhesus macaque monocyte-derived DC, we show that nucleofection is a superior method for mRNA transfection, resulting in high-level protein expression and DC maturation. DC transfected with SIV gag isolated from an infected monkey stimulated robust Ag-specific recall T cell responses of similar magnitude to those induced by peptide-pulsed PBMC that were predominantly CD8 + T cell mediated. Enhanced CD4 + T cell responses were stimulated when Gag was redirected into the lysosomal pathway via the targeting signal derived from lysosome-associated membrane protein-1 (LAMP-1). Rhesus DC transfected with lysosome-targeted gag encoding an escape mutation in an immunodominant CTL epitope stimulated CD4 + and CD8 + T cell responses of almost equivalent magnitude directed towards undefined epitopes outside of the mutated region. Finally, gag-transfected DC from SIV-infected monkeys stimulated significant Ag-specific recall T cell responses in an entirely autologous system. These findings demonstrate that mRNA-transfected DC expressing SIV Ag derived from infected monkeys stimulate broad and relevant T cell responses, supporting this approach for therapeutic HIV vaccine development. IntroductionIt is well appreciated that strong CD4 + and CD8 + T cell immunity is required for control of HIV infection [1][2][3][4][5], and therapeutic vaccines designed to promote broad cellular immune responses are being actively pursued [6]. However, an important challenge in the development of vaccines for HIV is the diversity of clinical isolates [7] coupled with the propensity for the virus to undergo escape mutations in T cell epitopes through selective pressure in vivo [8]. Hence, CTL induced in response to the infecting strain may be incapable of controlling circulating virus as infection progresses [9][10][11][12]. To account for this complexity, a therapeutic vaccine should be tailored towards the autologous virus present in an individual at the time of immunotherapy. An attractive alternative source of viral Ag for therapeutic DC-based vaccination is mRNA, an approach that has been developed in the cancer immunotherapy field [23,24]. DC transfected with codon-optimized HIV mRNA have been shown to induce strong T cell immune responses in vitro [25,26] with enhanced CD4 + T cell responses arising from DC expressing lysosome-targeted Ag [27]. DC transfected with autologous viral mRNA isolated from HIV-infected individuals induce significant virus-specific T cell responses [25]. The rhesus macaque SIV model provides an ideal preclinical setting to test the therapeutic potential of DC-based vaccines using virusderived mRNA. Here, we evaluated the capacity of mRNA-transfected DC to stimulate T cell responses against SIV using an in vitro system. We adopted a new electroporation ...

Global sequencing and surveillance capacity for SARS-CoV-2 must be strengthened and combined with multidisciplinary studies of infectivity, virulence and immune escape, in order to track the unpredictable evolution of the ongoing COVID-19 pandemic.

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