bims-inflim 2018-04-01 papers

Issue of 2018–04–01
four papers selected by
Christine Oshansky-Weilnau

Biologicals. 2018 Mar 21. pii: S1045-1056(18)30039-3. [Epub ahead of print]

Human challenge trials in vaccine development, Rockville, MD, USA, September 28-30, 2017.

Session chairs at the second Human Challenge Trials meeting

The International Alliance for Biological Standardization organized the second workshop on human challenge trials (HCT) in Rockville, MD, in September 2017. The objective of this meeting was to examine the use of HCT, in response to the continuing human suffering caused by infectious diseases, preventable by the development of new and improved vaccines. For this, the approach of HCT could be valuable, as HCT can provide key safety, tolerability, immunogenicity, and efficacy data, and can be used to study host-pathogen biology. HCT can generate these data with speed, efficiency and minimal expense, albeit not with the same level of robustness as clinical trials. Incorporated wisely into a clinical development plan, HCT can support optimization or down-selection of new vaccine candidates, assuring that only the worthiest candidates progress to field testing. HCT may also provide pivotal efficacy data in support of licensure, particularly when field efficacy studies are not feasible. Many aspects of HCT were discussed by the participants, including new and existing models, standardization and ethics. A consensus was achieved that HCT, if ethically justified and performed with careful attention to safety and informed consent, should be pursued to promote and accelerate vaccine development.

Keywords: Efficacy; Ethics; Human challenge; Infection models; Vaccine

DOI: https://doi.org/10.1016/j.biologicals.2018.02.002

Virology. 2018 Mar 22. pii: S0042-6822(18)30094-1. [Epub ahead of print]518 313-323

Broadly protective anti-hemagglutinin stalk antibodies induced by live attenuated influenza vaccine expressing chimeric hemagglutinin.

Irina Isakova-Sivak, Daniil Korenkov, Tatiana Smolonogina, Tatiana Kotomina, Svetlana Donina, Victoria Matyushenko, Daria Mezhenskaya, Florian Krammer, Larisa Rudenko.

The development of influenza vaccines that can provide broad protection against all drifted seasonal virus variants, zoonotic infections and emerging pandemic strains, has been a priority for two decades. Here we propose a strategy of inducing broadly-reactive anti-stalk antibody by sequential immunizations with live attenuated influenza vaccines (LAIVs) expressing chimeric HAs (cHAs). These vaccines are designed to contain identical hemagglutinin stalk domains from H1N1 virus but antigenically unrelated globular head domains from avian influenza virus subtypes H5, H8 and H9. Mouse experiments demonstrated enhanced cross-protection of cHA-containing LAIVs compared to the relevant vaccine viruses expressing natural HAs, and this enhanced protection was driven by stalk-HA-reactive IgG antibodies. The establishment of fully functional cross-protective immunity after two doses of cHA LAIV vaccination in naïve animals suggests that a similar effect might be expected after a single cHA LAIV dose in primed individuals, or after two to three doses in naïve children.

Keywords: Anti-stalk antibody; Chimeric hemagglutinin; Cross-protection; Live attenuated influenza vaccine; Mouse model; Universal influenza vaccine

DOI: https://doi.org/10.1016/j.virol.2018.03.013

Virus Genes. 2018 Mar 24.

Differences in Type I interferon response in human lung epithelial cells infected by highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses.

Milind M Thube, Pratip Shil, Rewati Kasbe, Avinash A Patil, Shailesh D Pawar, Jayati Mullick.

Influenza A virus infection induces type I interferons (IFNs α/β) which activate host antiviral responses through a cascade of IFN signaling events. Herein, we compared highly pathogenic H5N1 and low pathogenic H11N1 avian influenza viruses isolated from India, for their replication kinetics and ability to induce IFN-β and interferon-stimulating genes (ISGs). The H5N1 virus showed a higher replication rate and induced less IFN-β and ISGs compared to the H11N1 virus when grown in the human lung epithelial A549 cells, reflecting the generation of differential innate immune responses during infection by these viruses. The non-structural 1 (NS1) protein, a major IFN-antagonist, known to help the virus in evading host innate immune response was compared from both the strains using bioinformatics tools. Analyses revealed differences in the composition of the NS1 proteins from the two strains that may have an impact on the modulation of the innate immune response. Intriguingly, H5N1 virus attenuated IFN-β response in a non-NS1 manner, suggesting the possible involvement of other viral proteins (PB2, PA, PB1/PB1-F2) of H5N1 in synergy with NS1. Preliminary analyses of the above proteins of the two strains by sequence comparison show differences in charged residues. The insight gained will be useful in designing experimental studies to elucidate a probable role of the polymerase protein(s) in association with NS1 in inhibiting the IFN signaling and understanding the molecular mechanism governing the difference.

Keywords: Avian influenza; CPSF30; H11N1; H5N1; Influenza; Innate immune response; Interferon; NS1

DOI: https://doi.org/10.1007/s11262-018-1556-1

Vaccine. 2018 Mar 21. pii: S0264-410X(18)30368-2. [Epub ahead of print]

T-cell responses against Malaria: Effect of parasite antigen diversity and relevance for vaccine development.

Omarine Nfor Nlinwe, Kwadwo Asamoah Kusi, Bright Adu, Martha Sedegah.

The on-going agenda for global malaria elimination will require the development of additional disease control and prevention measures since currently available tools are showing signs of inadequacy. Malaria vaccines are seen as one such important addition to the control arsenal since vaccines have proven to be highly effective public health tools against important human diseases. Both cell-mediated and antibody responses are generally believed to be important for malaria parasite control, although the exact targets of T and B cell responses against malaria have not been clearly defined. However, our current understanding of the immune response to malaria suggests that T cell responses against multiple antigenic targets may potentially be key for the development of a highly efficacious malaria vaccine. This review takes a comprehensive look at the available literature on T cell-mediated immunity against all human stages of the malaria parasite and the effect of antigen diversity on these responses. The implications of these interrelationships for the development of an effective vaccine for malaria are also highlighted.

Keywords: Antigen diversity; Malaria; T-cell; Vaccine development

DOI: https://doi.org/10.1016/j.vaccine.2018.03.023