Immune-mediated attenuation of influenza illness after infection: opportunities and challenges

Abstract

Sterilising immunity that blocks infection for life, and thus prevents illness after infection, is the ultimate goal for vaccines. Neither influenza infection nor vaccination provide sterilising immunity. Mutations during influenza viral genome replication result in the emergence of viruses that evade immunity and cause reinfections. Waning of immunity also results in reinfections to homologous influenza viruses. However, immunity might limit the severity of disease after infection or vaccination (ie, immunoattenuation). We provide a comprehensive examination of experimental and observational peer reviewed evidence since 1933, when the first influenza virus was isolated, on whether immunity blocks subsequent infection or attenuates illness. Although an abundance of experimental evidence supports immunoattenuation, clinical evidence is rudimentary and conflicting. To the extent that immunoattenuation occurs, understanding the varied pathways to illness, pathogenesis, clinical manifestations, and correlates of attenuation can improve the design and evaluation of influenza vaccines. By elucidating the mechanisms of immunoattenuation and phenotypes of illness, we clarify ambiguities and identify unmet needs that, if addressed with priority, could strategically improve the design of vaccines for the prevention of influenza."The chief danger in human influenza lies not in the effect of the virus on the nasal mucosa but in the tendency to lung involvement and if the presence of circulating antibodies is a check upon such pulmonary involvement it is possible that their production in man by vaccine inoculations would have some influence upon the mortality-rate of an epidemic even if it had no influence upon the morbidity." 1

BNT162b2 Protection against the Omicron Variant in Children and Adolescents

“…Breakthrough infections can occur in persons who have been vaccinated against respiratory viruses such as SARS-CoV-2 and influenza because sterilizing immunity providing lifelong protection against infection is untenable; variants can emerge against which vaccine-induced antibodies have reduced neutralization efficiency, and preexisting antibodies wane with time. 27 , 28 However, these breakthrough infections would be expected to invoke memory B- and T-cell responses, which can limit the progression of disease. 29-31 Our findings support the premise that vaccination-induced immunity attenuated Covid-19 disease severity without fully eliminating the risk of breakthrough infections in vaccinated children and adolescents.…”

Effectiveness of mRNA Vaccination in Preventing COVID-19–Associated Invasive Mechanical Ventilation and Death — United States, March 2021–January 2022

“…SARS-CoV-2 infection, like that from other respiratory viruses, is manifested by a gradient in illness severity, ranging from asymptomatic or mild infection to critical or fatal complications ( 2 , 5 ). Protection against asymptomatic or milder infection might be reduced by waning of neutralizing antibody levels after vaccination or by immune evasion by emerging variants ( 6 , 7 ).…”

Assessing vaccine effectiveness against severe COVID-19 disease caused by omicron variant. Report from a meeting of the World Health Organization

“…First, SARS-CoV-2 infection can trigger an exacerbation of underlying medical conditions, such as chronic lung or heart disease, as occurs with other respiratory viruses, such as influenza and respiratory syncytial virus. [30] , [31] , [32] Second, SARS-CoV-2 infection can occur incidentally among persons hospitalized for non-Covid-19 illnesses, where SARS-CoV-2 infection is not in the causal chain leading to admission. With the large omicron wave, which was typically larger than all pre-omicron waves, but with reduced severity, the likelihood of COVID-19 diagnosis coincidental with hospital admission increased.…”