Comparison of Heterosubtypic Protection in Ferrets and Pigs Induced by a Single-Cycle Influenza Vaccine

Abstract

Influenza is a major health threat, and a broadly protective influenza vaccine would be a significant advance. Signal Minus FLU (S-FLU) is a candidate broadly protective influenza vaccine that is limited to a single cycle of replication, which induces a strong cross-reactive T cell response but a minimal Ab response to hemagglutinin after intranasal or aerosol administration. We tested whether an H3N2 S-FLU can protect pigs and ferrets from heterosubtypic H1N1 influenza challenge. Aerosol administration of S-FLU to pigs induced lung tissue-resident memory T cells and reduced lung pathology but not the viral load. In contrast, in ferrets, S-FLU reduced viral replication and aerosol transmission. Our data show that S-FLU has different protective efficacy in pigs and ferrets, and that in the absence of Ab, lung T cell immunity can reduce disease severity without reducing challenge viral replication.

Guidelines for the use of flow cytometry and cell sorting in immunological studies (second edition)

“…In lymph nodes, T cells with a naïve phenotype dominate, whereas in non‐lymphatic organs effector (memory) phenotypes are enriched . Recently, tissue‐resident memory T cells were described in porcine lung tissue and bronchoalveolar lavage . Abs for porcine CD103 are currently not available and pig‐specific mAbs for CD69 were described just recently but are not yet commercialized.…”

Evaluation of the immunogenicity of prime-boost vaccination with the replication-deficient viral vectored COVID-19 vaccine candidate ChAdOx1 nCoV-19

“…A single dose of ChAdOx1 nCoV-19 induces antibody responses, but we demonstrate here that antibody responses are significantly enhanced after homologous boost in one mouse strain and to a greater extent in pigs. However, it is likely that a combination of neutralising antibodies and antigen-specific T cells would act in synergy to prevent and control infection, as we have recently shown in the context of influenza vaccination 13,25 .…”

“…The mouse data generated in this study suggested that the immunogenicity profile was at the upper end of a dose response curve, which may have saturated the immune response and largely obscured our ability to determine differences between prime-only or prime-boost regimens. We have developed the pig as a model for generating and understanding immune responses to vaccination against human influenza [13][14][15] and Nipah virus 16,17 .The inherent heterogeneity of an outbred large animal model is more representative of immune responses in humans. Extensive development of reagents to study immune responses in pigs in recent years has extended the usefulness and applicability of the pig as a model to study infectious disease.…”

Immune Responses to Avian Influenza Viruses

“…As the currently licensed inactivated influenza vaccines do not boost CD8 + T cells or innate T cells (113), novel vaccination strategies that elicit cross-reactive memory T cells are highly desirable to provide universal immunity against current and emerging influenza viruses. Several approaches are under development, including replication-incompetent viruses that are able to infect cells but are limited to a single cycle of replication because one or more of the genes that are essential for viral replication have been deleted or silenced (114)(115)(116)(117)(118) and vectored vaccines that encode one or more internal protein genes of influenza (119). There is no doubt that T cell immunity is more cross-reactive than HA Ab-mediated immunity.…”