Cross-protective immunity to influenza A viruses

Abstract

Antigenic changes in influenza virus occur gradually, owing to mutations (antigenic drift), and abruptly, owing to reassortment among subtypes (antigenic shift). Availability of strain-matched vaccines often lags behind these changes, resulting in a shortfall in public health. In animal models, cross-protection by vaccines based on conserved antigens does not completely prevent infection, but greatly reduces morbidity, mortality, virus replication and, thus, viral shedding and spread. Such immunity is especially effective and long-lasting with mucosal administration. Cross-protective immunity in humans is controversial, but is suggested by some epidemiological findings. 'Universal' vaccines protective against all influenza A viruses might substantially reduce severity of infection and limit spread of disease during outbreaks. These vaccines could be used 'off the shelf' early in an outbreak or pandemic, before strain-matched vaccines are available.

Memory CD4+ T cells protect against influenza through multiple synergizing mechanisms

“…Most current vaccines aim to generate neutralizing Ab against predicted seasonal IAV and often fail to induce or boost T cell responses (47). The ability of memory CD4 + T cells to engage in multiple mechanisms of protection that together provide potent protection even in the absence of both memory B and CD8 + T cells suggests that inducing memory CD4 + T cells through vaccination deserves strong consideration.…”

Impact of cross-protective vaccines on epidemiological and evolutionary dynamics of influenza

“…There is therefore increasing interest in developing vaccines targeting viral proteins more conserved than currently targeted HA epitopes (10)(11)(12)(13)(14). By inducing immunity against different subtypes of influenza, and different strains of the same subtype, such vaccines do not require knowledge of what strain is emerging; they could thus provide better pandemic and epidemic mitigation than antiviral drugs or social distancing (15), by permitting longterm suppression of transmission.…”

“…There are many different cross-protective vaccine candidates under study (10)(11)(12)(13)(14). Such vaccines do not necessarily prevent infection, but can be effective in reducing viral shedding, and can greatly reduce morbidity and mortality in animal models (10,11).…”

“…Such vaccines do not necessarily prevent infection, but can be effective in reducing viral shedding, and can greatly reduce morbidity and mortality in animal models (10,11). Fig.…”

Influenza viruses

“…2 However, antibodies against more conserved regions of the HA protein or of other viral proteins may confer protection against antigenically more distant influenza viruses. 102 Likewise, the other arm of the immune system, and in particular memory T-lymphocytes, such as CD8+ cytotoxic T-lymphocytes, may not only confer subtypic, but also heterosubtypic immunity. These cells contribute to increased and more rapid clearance upon infection with influenza viruses, including those of different subtypes.…”