Implications of Intranasal Polyvalent Vaccination for Pulmonary Alveolar Macrophage and Neutrophil Functions in Calves

Background: Vaccines undoubtedly represent a promising and much needed approach to combatting infectious diseases, but there is also increasing evidence that they exert nonspecific effects, and these effects may be beneficial but also sometimes detrimental. Thus, here we sought to explore the effect of intranasal vaccination on the functions of pulmonary alveolar macrophages and neutrophils in calves of different ages.Results: Respiratory clinical signs and impaired microbicidal and phagocytic activities were observed for the alveolar neutrophils and vacuolized macrophages in the vaccinated calves compared with those in the unvaccinated calves, particularly at 15 days of age.Conclusions: Our results indicated that the use of some polyvalent attenuated and modified live virus vaccines in early stage of calves’ life, especially those under 15 days of age, should be restricted to farms in which the cattle are at a higher risk of contracting these viral infections, particularly considering the importance of alveolar macrophages and neutrophils against bacterial pathogens in a period of intense pulmonary challenge.

Broadly neutralizing plasma antibodies effective against diverse autologous circulating viruses in infants with multivariant HIV-1 infection

Due to the extensive antigenic diversity of human immunodeficiency virus-1 (HIV-1), broadly neutralizing antibodies (bnAbs) develop in a subset of infected individuals over 2-3 years of infection. Interestingly, infected infants have been shown to develop plasma bnAbs frequently and as early as one-year post-infection, with features atypical than adult bnAbs, suggesting that the factors governing bnAb induction in infants are distinct from that in adults. Understanding the viral characteristics in infected infants with early bnAb responses will provide key information on the antigenic triggers driving B cell maturation pathways towards the induction of bnAbs. Herein, we evaluated the presence of plasma bnAbs in a cohort of 51 HIV-1 clade C perinatally infected infants of Indian origin and identified viral factors associated with early bnAb responses. Plasma bnAbs targeting V2-apex on the env were predominant in infant elite and broad neutralizers. Circulating viral variants in infant elite neutralizers were susceptible to known bnAbs against V2-apex while varied resistance profile to other bnAb classes was observed. In infant elite neutralizers, multivariant infection was associated with plasma bnAbs targeting diverse autologous viruses. Our data provides information supportive of polyvalent vaccination approaches capable of inducing V2-apex bnAbs against HIV-1.

A single cycle influenza virus coated in H7 hemagglutinin provides heterotypic protection and neutralising antibody responses to both glycoproteins

A non-replicating form of pseudotyped influenza virus, inactivated by suppression of the hemagglutinin signal sequence (S-FLU), can act as a broadly protective vaccine. S-FLU can infect for a single round only, and induces heterotypic protection predominantly through activation of cross-reactive T cells in the lung. Unlike the licensed live attenuated virus, it cannot reassort a pandemic HA into seasonal influenza. Here we present data on four new forms of S-FLU coated with the H7 hemagglutinins from A/Anhui/1/2013 and A/Shanghai/1/2013, H7N9 viruses that emerged recently in China, and A/Netherlands/219/2003 and A/New York/107/2003. We show that vaccination in the lung induced a strong local CD8 T cell response and protected against heterosubtypic X31 (H3N2) virus and highly virulent PR8 (H1N1), but not influenza B virus. Lung vaccination also induced a strong neutralising antibody response to the encoded neuraminidase. If given at higher dose in the periphery, H7 S-FLU induced a specific neutralising antibody response to H7 hemagglutinin coating the particle. Polyvalent vaccination with mixed H7 S-FLU induced a broadly neutralising antibody response to all four H7 strains. S-FLU is a versatile vaccine candidate that could be rapidly mobilized ahead of a new pandemic threat.

Impact of the lymphoma idiotype on in vivo tumor protection in a vaccination model based on targeting antigens to antigen-presenting cells

Trioma cell vaccination is a potent new immunologic approach for the therapy of malignant B-cell lymphoma. It is based on targeting tumor antigens to internalizing receptors on antigen-presenting cells (APCs). Tumor cells are fused to an APC-specific hybridoma, where they are converted to trioma cells that include potentially all lymphoma-derived antigens and that express the APC-binding arm. In this study, the mechanisms of trioma-mediated tumor immunity in immunocompetent mice were dissected, and it was shown in this model system that humoral anti-idiotypic immunity is indeed detectable after idiotype-specific immunization but that it does not reflect the degree of tumor protection obtained in vivo. Immunization against the idiotype alone was not sufficient for efficient tumor rejection in vivo. Targeting tumor antigens to APCs is only successful in terms of inducing tumor protection when designed as a polyvalent vaccination protocol.