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Influenza A virus is one of the most important zoonotic pathogens that can cause severe symptoms and has the potential to cause high number of deaths and great economic loss. Vaccination is still the best option to prevent influenza virus infection. Different types of influenza vaccines, including live attenuated virus vaccines, inactivated whole virus vaccines, virosome vaccines, split-virion vaccines and subunit vaccines have been developed. However, they have several limitations, such as the relatively high manufacturing cost and long production time, moderate efficacy of some of the vaccines in certain populations, and lack of cross-reactivity. These are some of the problems that need to be solved. Here, we summarized recent advances in the development and application of different types of influenza vaccines, including the recent development of viral vectored influenza vaccines. We also described the construction of other vaccines that are based on recombinant influenza viruses as viral vectors. Information provided in this review article might lead to the development of safe and highly effective novel influenza vaccines., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Chen, Wang, Zhang and Ly.)

There is a constant threat of zoonotic influenza viruses causing a pandemic outbreak in humans. It is virtually impossible to predict which virus strain will cause the next pandemic and it takes a considerable amount of time before a safe and effective vaccine will be available once a pandemic occurs. In addition, development of pandemic vaccines is hampered by the generally poor immunogenicity of avian influenza viruses in humans. An effective pre-pandemic vaccine is therefore required as a first line of defense. Broadening of the protective efficacy of current seasonal vaccines by adding an adjuvant may be a way to provide such first line of defense. Here we evaluate whether a seasonal trivalent virosomal vaccine (TVV) adjuvated with the saponin-based adjuvant Matrix-M (MM) can confer protection against avian influenza H5 and H7 virus strains in mice and ferrets. We demonstrate that mice were protected from death against challenges with H5N1 and H7N7, but that the protection was not complete as evidenced by severe clinical signs. In ferrets, protection against H7N9 was not observed. In contrast, reduced upper and lower respiratory tract viral loads and reduced lung pathology, was achieved in H5N1 challenged ferrets. Together these results suggest that, at least to some extent, Matrix-M adjuvated seasonal virosomal influenza vaccine can serve as an interim measure to decrease morbidity and mortality associated with a pandemic outbreak.

Seasonal influenza is an annual challenge for health-care systems, due to factors such as co-circulation of 2 influenza A subtypes jointly with 2 influenza B lineages; the antigenic drift of these virus, which eludes natural immunity, as well as immunity conferred by vaccination; together with influenza impact in terms of morbidity and mortality. Influenza vaccines have been available for more than 70 years and they have progressed in formulation, production and delivery route. Recommendations on vaccination are focused on those with a higher probability of severe disease, and have a progressively wider coverage, and classically based on inactivated vaccines, but with an increasing importance of attenuated live vaccines. More inactivated vaccines are becoming available, from adyuvanted and virosomal vaccines to intradermal delivery, cell-culture or quadrivalent. Overall vaccine effectiveness is about 65%, but varies depending on characteristics of vaccines, virus, population and the outcomes to be prevented, and ranges from less than 10% to almost 90%. Future challenges are formulations that confer more extensive and lasting protection, as well as increased vaccination coverage, especially in groups such as pregnant women and health-care professionals, as well as being extended to paediatrics., (Copyright © 2015 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.)

Adjuvants can stimulate vaccine-induced immune responses and can contribute decisively to antigen dose sparing when vaccine antigen production is limited, as for example during a pandemic influenza outbreak. We earlier showed that GPI-0100, a semi-synthetic saponin derivative with amphiphilic structure, significantly stimulates the immunogenicity and protective efficacy of influenza subunit vaccine administered via a systemic route. Here, we evaluated the adjuvant effect of GPI-0100 on a virosomal influenza vaccine formulation. In contrast to influenza subunit vaccine adjuvanted with GPI-0100, virosomal vaccine supplemented with the same dose of GPI-0100 provided full protection of mice against infection at the extremely low antigen dose of 2 × 8 ng hemagglutinin. Overall, adjuvanted virosomes elicited higher antibody and T-cell responses than did adjuvanted subunit vaccine. The enhanced immunogenicity of the GPI-0100-adjuvanted virosomes, particularly at low antigen doses, is possibly due to a physical association of the amphiphilic adjuvant with the virosomal membrane. These results show that a combination of GPI-0100 and a virosomal influenza vaccine formulation is highly immunogenic and allows the use of very low antigen doses without compromising the protective potential of the vaccine.

The World Health Organisation (WHO) estimates that seasonal influenza affects approximately 5-15% of the population on an annual basis and these outbreaks are responsible for significant morbidity and mortality resulting in increased hospital admissions. Annual vaccination remains the main public health strategy for containing influenza. Inactivated influenza vaccines offer a great deal of protection against influenza but these vaccines are not optimal for older adults due to their waning immunity and other factors affecting immunogenicity. Virosomes, stimulate the immune system in a similar way as a natural infection and studies have shown that the virosomal adjuvanted influenza vaccine is immunogenic and safe in different population groups including: the elderly, children and immunocompromised subjects. Currently available data suggest improved immunogenicity of the virosomal adjuvanted vaccine in the elderly and in subjects without protective antibody as compared to conventional vaccines.

In spite of the efforts of the World Health Organization (WHO), influenza continues to be a major public health problem, both because of its impact on the health of subjects at risk, such as the elderly, and because of the economic burden that it places on society. Adjuvants are agents which, when incorporated into vaccines, enhance the immunogenicity of their antigens. The need for ever more immunogenic and efficacious influenza vaccines has led to the development of innovative vaccines. One of these, the virosomal vaccine, has been on the market since 1997. The results obtained through controlled clinical studies and widespread application in the field suggest that the virosomal vaccine is not only an important tool for the prevention of seasonal influenza but also a valid means of potentiating the effect of a pandemic influenza vaccine and, perhaps, of preparing multivalent or combined vaccines.

The potential as prophylactic vaccines of L1-based particles from cutaneous genus alpha human papillomavirus (HPV) types has not been assessed so far. However, there is a high medical need for such vaccines since HPV-induced skin warts represent a major burden for children and for immunocompromised adults, such as organ transplant recipients. In this study, we have examined the immunogenicity of capsomeres and virus-like particles (VLPs) from HPV types 2, 27, and 57, the most frequent causative agents of skin warts. Immunization of mice induced immune responses resembling those observed upon vaccination with HPV 16 L1-based antigens. The antibody responses were cross-reactive but type-restricted in their neutralizing capacities. Application of adjuvant led to an enhanced potential to neutralize the respective immunogen type but did not improve cross-neutralization. Vaccination with capsomeres and VLPs from all four analyzed HPV types induced robust IFNgamma-associated T-cell activation. Immunization with mixed VLPs from HPV types 2, 27, and 57 triggered an antibody response similar to that after single-type immunization and capable of efficiently neutralizing all three types. Our results imply that vaccination with combinations of VLPs from cutaneous HPV types constitutes a promising strategy to prevent HPV-induced skin lesions., (Copyright (c) 2009 Elsevier Ltd. All rights reserved.)

Influenza is associated with substantial morbidity and mortality in adults aged over 65 years. Although vaccination remains the most effective method of preventing influenza and its sequellae, current vaccination strategies provide less protection to older adults than to younger persons. Influenza vaccination in community-dwelling older adults is cost-effective, though there is room for improvement. Newer vaccine strategies considered for use in older adults include alternate routes of administration (intradermal or intranasal), addition of adjuvant, and novel methods of antigen presentation. Measuring cell-mediated immune response to new vaccines in addition to antibody response may correlate better with vaccine efficacy in this population. Whilst pandemic influenza A/H1N1 2009 (pH1N1) has largely spared older adults, the impact of pH1N1 vaccination has yet to be determined.

During the last decade, the propagation of immunological knowledge describing the critical role of dendritic cells (DC) in the induction of efficacious immune responses has promoted research and development of vaccines systematically targeting DC. Based on the promise for the rational design of vaccine platforms, the current review will provide an update on particle-based vaccines of both viral and synthetic origin, giving examples of recombinant virus carriers such as adenoviruses and biodegradable particulate carriers. The viral carriers carry pathogen-associated molecular patterns (PAMP), used by the original virus for targeting DC, and are particularly efficient and versatile gene delivery vectors. Efforts in the field of synthetic vaccine carriers are focussing on decorating the particle surface with ligands for DC receptors such as heparan sulphate glycosaminoglycan structures, integrins, Siglecs, galectins, C-type lectins and toll-like receptors. The emphasis of this review will be placed on targeting the porcine immune system, but reference will be made to advances with murine and human vaccine delivery systems where information on DC targeting is available.

Virus-specific CD8(+) T cells are thought to play an important role in resolving acute hepatitis C virus (HCV) infection as viral clearance has been associated with a strong and sustained CD8(+) T cell response. During the chronic state of HCV infection virus-specific T cells have a low frequency and a reduced responsiveness. Based on this, a therapeutic vaccine increasing the frequency of specific T cells is a promising alternative for the treatment of chronic HCV infection. We improved an existing vaccine platform based on immunopotentiating reconstituted influenza virosomes (IRIVs) for efficient delivery of peptide epitopes to the MHC class I antigen presentation pathway. IRIVs are proteoliposomes composed of phospholipids and influenza surface glycoproteins. Due to their fusogenic activity, IRIVs are able to deliver encapsulated macromolecules, e.g. peptides to immunocompetent cells. We developed a novel method based on chimeric virosomes [chimeric immunopotentiating reconstituted influenza virosomes (CIRIVs)] combining the high peptide-encapsulation capacity of liposomes and the fusion activity of virosomes. This new approach resulted in a 30-fold increase of the amount of incorporated soluble peptide compared with current preparation methods. To study the immunogenicity of chimeric virosomes HLA-A2.1 transgenic mice were immunized with CIRIVs containing the HCV Core132 peptide. Core132-CIRIVs efficiently induced specific cytotoxic and IFNgamma-producing T cells already with low peptide doses. Vaccine formulations, which include combinations of different HCV-derived CTL epitopes could be used to induce not only a strong but also a multi-specific CTL response, making them potential candidates for therapeutic and maybe prophylactic T cell vaccines in humans.