The respiratory mucosa is the primary portal of entry for numerous viruses such as the respiratory syncytial virus, the influenza virus and the parainfluenza virus. These pathogens initially infect the upper respiratory tract and then reach the lower respiratory tract, leading to diseases. Vaccination is an affordable way to control the pathogenicity of viruses and constitutes the strategy of choice to fight against infections, including those leading to pulmonary diseases. Conventional vaccines based on live-attenuated pathogens present a risk of reversion to pathogenic virulence while inactivated pathogen vaccines often lead to a weak immune response. Subunit vaccines were developed to overcome these issues. However, these vaccines may suffer from a limited immunogenicity and, in most cases, the protection induced is only partial. A new generation of vaccines based on nanoparticles has shown great potential to address most of the limitations of conventional and subunit vaccines. This is due to recent advances in chemical and biological engineering, which allow the design of nanoparticles with a precise control over the size, shape, functionality and surface properties, leading to enhanced antigen presentation and strong immunogenicity. This short review provides an overview of the advantages associated with the use of nanoparticles as vaccine delivery platforms to immunize against respiratory viruses and highlights relevant examples demonstrating their potential as safe, effective and affordable vaccines.

The kinetics of appearance of antibodies directed to the major structural proteins N, M and E of porcine reproductive and respiratory syndrome virus (PRRSV) was followed in pigs naturally- and experimentally-exposed to the virus. Specific IgM antibody titers were first detected by indirect immunofluorescence (IIF) at the end of the first week of PRRSV infection, peaked by day 14 to 21 post-inoculation (p.i.), then rapidly decreased to undetectable levels by day 35 to 42 p.i. On the other hand, specific IgG antibody titers peaked by day 21 to 28 p.i. and remained unchanged to the end of the 6- or 9-week observation period; in addition, a persistent viremia was observed. Virus neutralizing (VN) antibody titers > 8 were not detected until 3 to 4 weeks p.i. Taken together, the results obtained by Western blotting analyses using purified virus and E. coli-expressed ORFs 5 to 7 gene products, suggested that antibodies directed against the envelope E protein appear by day 7 p.i., whereas antibodies directed against the nucleocapsid N and membrane M proteins can only be detected by the end of the second week p.i. No correlation could be demonstrated between VN and IIF antibody titers, viremia, and viral protein specificities of circulating antibodies at various times p.i.

This study demonstrated the capacity of bacteriocin-producing lactic acid bacteria (LAB) to reduce intestinal colonization by vancomycin-resistant enterococci (VRE) in a mouse model. Lactococcus lactis MM19 and Pediococcus acidilactici MM33 are bacteriocin producers isolated from human feces. The bacteriocin secreted by P. acidilactici is identical to pediocin PA-1/AcH, while PCR analysis demonstrated that L. lactis harbors the nisin Z gene. LAB were acid and bile tolerant when assayed under simulated gastrointestinal conditions. A well diffusion assay using supernatants from LAB demonstrated strong activity against a clinical isolate of VRE. A first in vivo study was done using C57BL/6 mice that received daily intragastric doses of L. lactis MM19, P. acidilactici MM33, P. acidilactici MM33A (a pediocin mutant that had lost its ability to produce pediocin), or phosphate-buffered saline (PBS) for 18 days. This study showed that L. lactis and P. acidilactici MM33A increased the concentrations of total LAB and anaerobes while P. acidilactici MM33 decreased the Enterobacteriaceae populations. A second in vivo study was done using VRE-colonized mice that received the same inocula as those in the previous study for 16 days. In L. lactis-fed mice, fecal VRE levels 1.73 and 2.50 log 10 CFU/g lower than those in the PBS group were observed at 1 and 3 days postinfection. In the P. acidilactici MM33-fed mice, no reduction was observed at 1 day postinfection but a reduction of 1.85 log 10 CFU/g was measured at 3 days postinfection. Levels of VRE in both groups of mice treated with bacteriocin-producing LAB were undetectable at 6 days postinfection. No significant difference in mice fed the pediocin-negative strain compared to the control group was observed. This is the first demonstration that human L. lactis and P. acidilactici nisin-and pediocin-producing strains can reduce VRE intestinal colonization.

Bovine immunodeficiency virus (BIV) is a lentivirus of theRetroviridae family which shares morphological, genetic, antigenic, and/or biologic properties with human immunodeficiency virus type 1 (HIV-1) and other animal lentiviruses including equine infectious anemia virus (EIAV) (22,23,68). Although the association of clinical diseases with BIV is still controversial, persistent lymphocytosis, neurological disorders associated with central nervous system lesions, weight loss, diminished milk production, lymphoid hyperplasia, and the presence of opportunistic bacterial infections have been associated with BIV infection (5,47,57,70). Interestingly, studies of rabbits experimentally infected with BIV have shown the development of a disease characterized by a fatal dysfunction of the immune system similar to that observed in humans, nonhuman primates, and cats infected with HIV-1 (or HIV-2), simian immunodeficiency virus, and feline immunodeficiency virus, respectively (34,35).BIV is categorized as a complex nonprimate lentivirus (68). The BIV provirus DNA is 8,960 nucleotides in length with a typical retroviral genomic structure containing the gag, pol, and env genes flanked by long terminal repeats of 589 nucleotides in length at the 5Ј and 3Ј termini (23,68). In proximity to the pol/env junction, the BIV genome also contains additional open reading frames that may encode nonstructural regulatory/ accessory proteins (23,68). These open reading frames are designated vif (viral infectivity factor), tat (trans-activator factor of transcription), rev (regulator of virus expression), vpw, vpy, and tmx. Only the Tat and Rev proteins have been reported to regulate viral expression at the transcriptional and posttranscriptional levels, respectively (21)(22)(23)68). Among the latter proteins, only the Tat protein and its transactivator response element (TAR) located within the long terminal repeat sequence have been intensively studied (3,6,10,19,58,60,72).BIV Rev is a 23-kDa (186-aa-long) phosphoprotein produced from a multiply spliced mRNA that contains the untranslated leader (exon 1) and two encoding exons (exons 2 and 3) (55). It has been shown previously that BIV Rev localizes to the nucleus and nucleoli of BIV-infected cells (56). As reported for HIV-1 Rev, BIV Rev mediates the nuclear exportation of partially spliced viral RNAs encoding structural proteins and of unspliced RNAs that serve as genomic RNA by interacting with a stem-loop structure termed Rev-responsive element (RRE) present in these RNAs (59). The Rev proteins contain at least three central functional domains: a basic arginine-rich domain that mediates RNA binding (RBD) and contains the nuclear/nucleolar localization signal (NLS/NoLS), a multimerization domain, and a leucine-rich domain that is necessary for the nuclear exportation of Rev (51, 59).In HIV-1, the Rev protein shuttles between the nucleus and the cytoplasm of the infected cells via the importin/exportin proteins or nucleoporin pathway (59). The shuttling of HIV-1 Rev into the nucleus is m...