Viral vaccines focused on influenza and HIV

Vaccination against infectious diseases is one of the most powerful prophylactic measures to reduce morbidity and mortality.

Vaccines, in today’s modern forms, have been available since 1940's and the childhood vaccination efforts belong to the greatest medical achievements so far. However, we still have a number of infectious diseases, both old and new, that lack efficient enough vaccines. For this reason, we aim at performing research on how to develop new vaccine candidates against challenging microbes such as human immunodeficiency viruses type 1 (HIV-1) and influenza A/B viruses.

Not only will we need new vaccine products (i.e DNA-vaccines, Viral vectors, recombinant proteins), we should also consider how vaccines should be administered, instead of by syringe and needles (as most often today).

Since most of our infectious disease-causing agents infect us by mucosal routes, and our vaccines most often do not stimulate immune responses in the mucosal tissues, we support the idea of developing vaccination procedures that could be used to elicit both mucosal and systemic immunity against the infectious microorganisms. Some vaccine products are also too weak as immunogens by themselves to provide efficient immunity. In these cases, they may benefit by the use of vaccine-adjuvant combinations that stimulate immune responses.

Our work is thus focused on how to provide neutralizing antibodies, long-lasting memory B- and T-lymphocytes in mucosal tissues and lymphoid tissues against pathogenic microorganisms.

Research projects
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Research projects with the aim to develop New Viral vaccines against pathogens such as HIV-1 and influenza viruses.

Photo credit Magnus JohanssonVaccine candidates and adjuvants are tested in preclinical and clinical trials, and immunized individuals are then tested for their immune responses against the infectious viruses.

The research aims at identifying if the vaccines selected induce neutralizing antibodies in blood and on mucosal surfaces. Furthermore, we test the development of vaccine-specific cell-mediated T-lymphocyte immunity.

Assays that we perform are: Serological such as ELISA, virus-neutralization assays in vitro, hemagglutination inhibitions (HI) and cell-mediated immune assays such as cell-proliferations and ELIspot assays.

The seasonal flu vaccinations are now available for dependents and military members at the 354th Medical Clinic. H1N1 flu vaccinations will be available in limited supplies in late October, immunizing high risk individuals first. (U.S. Air Force photo/Staff Sgt. Tia Wilson) Photo credit Staff Sgt. Tia WilsonThe modes of how to deliver a vaccine is of great interest, so we perform various parenteral immunization techniques, such as injection by syringe and needle, but also by Biojector, SyriJet sprays, via electroporations and gold-particle biolistic immunizations and nasal spray/drops on different tissues from epidermis, subcutaneously, intramuscular and intranasal or oral deliveries.

Vaccine types that we previously have and are about to be tested are: Inactivated protein vaccines, live attenuated vaccine vectors, synthetic peptides, recombinant proteins and DNA-plasmids or RNA.

The vaccines against viruses we have worked with are:

  • Human immunodeficiency viruses type 1 (HIV-1)
  • Influenza A viruses
  • Rotaviruses
  • Papillomaviruses
  • Crimean Congo-Haemorragic fever virus (CCHFV)


Adjuvants are searched for to enhance the vaccine induced antigen-presentation via dendritic cells to obtain immune strengths and breaths to provide mucosal and systemic long-lasting immunity. Thus, the adjuvants need to be mild enough to avoid serious side effects, but still support the vaccine responses.

In our current research we are exploring the limitations and opportunities of vaccination in an aging immune system, such as can be seen in HIV-infected individuals, or in people of high age.

In conclusion; our research is to investigate which Viral vaccines work, and try to explain why.

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References

Jorma Hinkula, Sanna Nyström, Claudia Devito, Andreas Bråve and 
Steven E. Applequist. Long-Lasting Mucosal and Systemic Immunity Against Influenza A Virus Is Significantly Prolonged and Protective by Nasal Whole Influenza Immunization with Mucosal Adjuvant N3 and DNA-Plasmid Expressing Flagellin in Aging In- and Outbred Mice. Vaccines 2019, 7 in press.

Devito C, Ellegård R, Falkeborn T, Svensson L, Ohlin M, Larsson M, Broliden K, Hinkula JHuman IgM monoclonal antibodies block HIV-transmission to immune cells in cervico-vaginal tissues and across polarized epithelial cells in vitro. Sci. Rep. 2018 8(1):10180. Doi: 10.1038/s41598-018-28242-y

Hinkula J, Petkov S, Ljungberg K, Hallengärd D, Bråve A, Isagiliants M, Falkeborn T, Sharma S, Liakina V, Robb M, Eller M, Moss B, Biberfeld G, Sandström E, Nilsson C, Markland K, Blomberg P, Wahren B. HIVIS-DNA or HIVISopt-DNA priming followed by CDMR vaccinia-based boosts induce both humoral and cellular murine immune responses to HIV. Heliyon. 2017, 3(6):e00339. Doi:10.1016/j.heliyon.2017.e00339.

Rada Ellegård, Mohammad Khalid, Cecilia Svanberg, Hanna Holgersson, Ylva Thorén, Mirja Wittgren, Jorma Hinkula, Sofia Nyström, Esaki M. Shankar and Marie Larsson. Complement-Opsonized HIV-1 Alters Cross-Talk between Dendritic Cells and NK Cells to Inhibit the Killing Potentials of NK Cells, and Induces the Upregulation of PD-1, CXCR3, and CCR4 on T Cells. Front Immunol. 2018, 9:899. Doi.10.3389/fimmu.2018.00899.

Hinkula J, Devignot S, Åkerström S, Karlberg H, Wattrang E, Bereczky M, Mousavi-Jazi M, Risinger C, Lindegren G, Vernersson C, Paweska J, Jansen van Vuren P, Blixt O, Brun A, Weber F. Mirazimi A. Immunization with DNA plasmids coding for Crimean-Congo Hemorrhagic Fever virus capsid and envelope proteins induces protection and survival in challenged mice. J.Virol. 2017, pii:JVI.02076-16: doi:10.1128/JVI.02076-17

Research group
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Organisation
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