scholarly journals Earliest infections predict the age distribution of seasonal influenza A cases

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Philip Arevalo ◽  
Huong Q McLean ◽  
Edward A Belongia ◽  
Sarah Cobey
Keyword(s):  
Seasonal Variation ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Primary Infection ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Infection ◽  
Age Distribution ◽  
Vaccination Strategies ◽  
Original Antigenic Sin

Seasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza.

scholarly journals Earliest infections predict the age distribution of seasonal influenza A cases

2019 ◽  
Author(s):  
Philip Arevalo ◽  
Huong Q. McLean ◽  
Edward A. Belongia ◽  
Sarah Cobey
Keyword(s):  
Seasonal Variation ◽  
Immune Responses ◽  
Influenza Vaccine ◽  
Primary Infection ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Infection ◽  
Age Distribution ◽  
Vaccination Strategies ◽  
Original Antigenic Sin

AbstractSeasonal variation in the age distribution of influenza A cases suggests that factors other than age shape susceptibility to medically attended infection. We ask whether these differences can be partly explained by protection conferred by childhood influenza infection, which has lasting impacts on immune responses to influenza and protection against new influenza A subtypes (phenomena known as original antigenic sin and immune imprinting). Fitting a statistical model to data from studies of influenza vaccine effectiveness (VE), we find that primary infection appears to reduce the risk of medically attended infection with that subtype throughout life. This effect is stronger for H1N1 compared to H3N2. Additionally, we find evidence that VE varies with both age and birth year, suggesting that VE is sensitive to early exposures. Our findings may improve estimates of age-specific risk and VE in similarly vaccinated populations and thus improve forecasting and vaccination strategies to combat seasonal influenza.

scholarly journals Prior exposure to immunogenic peptides found in human influenza A viruses may influence the age distribution of cases with avian influenza H5N1 and H7N9 virus infections

2019 ◽  
Vol 147 ◽  
Author(s):  
N. Komadina ◽  
S. G. Sullivan ◽  
K. Kedzierska ◽  
S. M. Quiñones-Parra ◽  
K. Leder ◽  
...  
Keyword(s):  
Influenza A ◽  
H5n1 Virus ◽  
Seasonal Influenza ◽  
Influenza Infection ◽  
Age Distribution ◽  
Prior Exposure ◽  
H7n9 Virus ◽  
Age Related ◽  
Immunogenic Peptides ◽  
Older Populations

Abstract The epidemiology of H5N1 and H7N9 avian viruses of humans infected in China differs despite both viruses being avian reassortants that have inherited six internal genes from a common ancestor, H9N2. The median age of infected populations is substantially younger for H5N1 virus (26 years) compared with H7N9 virus (63 years). Population susceptibility to infection with seasonal influenza is understood to be influenced by cross-reactive CD8+ T cells directed towards immunogenic peptides derived from internal viral proteins which may provide some level of protection against further influenza infection. Prior exposure to seasonal influenza peptides may influence the age-related infection patterns observed for H5N1 and H7N9 viruses. A comparison of relatedness of immunogenic peptides between historical human strains and the two avian emerged viruses was undertaken for a possible explanation in the differences in age incidence observed. There appeared to be some relationship between past exposure to related peptides and the lower number of H5N1 virus cases in older populations, however the relationship between prior exposure and older populations among H7N9 virus patients was less clear.

scholarly journals Immunoglobulin G, A and M response to influenza vaccination in different age groups: effects of priming and boosting

1986 ◽  
Vol 96 (3) ◽  
pp. 513-522 ◽  
Author(s):  
Walter E. P. Beyer ◽  
Jos T. M. Van Der Logt ◽  
Ruud van Beek ◽  
Nic Masurel
Keyword(s):  
Antibody Response ◽  
Influenza Vaccine ◽  
Influenza A ◽  
Influenza Infection ◽  
Age Groups ◽  
Antibody Responses ◽  
Trivalent Influenza Vaccine ◽  
Antibody Capture ◽  
The Mean ◽  
Original Antigenic Sin

SUMMARYFifty volunteers, treated with an inactivated trivalent influenza vaccine containing A/Bangkok/1/79 (H3N2), A/Brazil/11/78 (H1N1) and B/Singapore/222/79 virus, were subdivided according to the estimated first exposure to influenza in their lifetime (priming) and the presence of antibodies against the vaccine components in the pre-vaccination sera. The isotypic antibody response (IgG, IgA, IgM) was determined by means of an antibody capture haemadsorption immunosorbent technique. For all three vaccine components, previously seropositive subjects produced antibodies of the IgG- and IgA-class more frequently than previously seronegative persons. Subjects primed to one of the influenza A subtypes showed more IgG and IgA responses in comparison with those unprimed (prime-effect). In contrast, IgM antibodies occurred in only 19 and 11% of primed, but in 59 and 54% of unprimed subjects, for A (H3N2) and A (HlNl), respectively. The incidence of IgM titre rises was not influenced by the prevaccination state. However, the mean magnitude of anti-A(H1N1)-IgM titre rises was greater in those previously seronegative. The concepts of primary and reinfection and of ‘original antigenic sin’ are discussed, and it is suggested that age and, if possible, serological state prior to antigen-exposure should be taken into account when studying isotypic antibody responses after influenza infection or vaccination.

scholarly journals Seasonal influenza vaccination and the risk of infection with pandemic influenza: a possible illustration of non-specific temporary immunity following infection

2010 ◽  
Vol 15 (47) ◽  
Author(s):  
H Kelly ◽  
S Barry ◽  
K Laurie ◽  
G Mercer
Keyword(s):  
Influenza Vaccine ◽  
Pandemic Influenza ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Infection ◽  
Risk Of Infection ◽  
Seasonal Influenza Vaccine ◽  
Influenza A H1n1 ◽  
Seasonal Infection ◽  
Temporary Immunity

Four Canadian studies have suggested that receipt of seasonal influenza vaccine increased the risk of laboratory-confirmed infection with 2009 pandemic influenza A(H1N1). During the influenza season of 2009 in Victoria, Australia, this virus comprised 97% of all circulating influenza viruses for which sub-typing was available. We found no evidence that seasonal influenza vaccine increased the risk of, or provided protection against, infection with the pandemic virus. Ferret experiments have suggested protection against pandemic influenza A(H1N1) 2009 from multiple prior seasonal influenza infections but not from prior seasonal vaccination. Modelling studies suggest that influenza infection leads to heterosubtypic temporary immunity which is initially almost complete. We suggest these observations together can explain the apparent discrepant findings in Canada and Victoria. In Victoria there was no recent prior circulation of seasonal influenza and thus no temporary immunity to pandemic influenza. There was no association of seasonal influenza vaccine with pandemic influenza infection. In Canada seasonal influenza preceded circulation of the pandemic virus. An unvaccinated proportion of the population developed temporary immunity to pandemic influenza from seasonal infection but a proportion of vaccinated members of the population did not get seasonal infection and hence did not develop temporary immunity to pandemic influenza. It may therefore have appeared as if seasonal vaccination increased the risk of infection with pandemic influenza A(H1N1) virus.

scholarly journals Next generation methodology for updating HA vaccines against emerging human seasonal influenza A(H3N2) viruses

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
James D. Allen ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Next Generation ◽  
Virus Infections ◽  
Wild Type ◽  
Influenza Hemagglutinin ◽  
H3n2 Influenza

AbstractWhile vaccines remain the best tool for preventing influenza virus infections, they have demonstrated low to moderate effectiveness in recent years. Seasonal influenza vaccines typically consist of wild-type influenza A and B viruses that are limited in their ability to elicit protective immune responses against co-circulating influenza virus variant strains. Improved influenza virus vaccines need to elicit protective immune responses against multiple influenza virus drift variants within each season. Broadly reactive vaccine candidates potentially provide a solution to this problem, but their efficacy may begin to wane as influenza viruses naturally mutate through processes that mediates drift. Thus, it is necessary to develop a method that commercial vaccine manufacturers can use to update broadly reactive vaccine antigens to better protect against future and currently circulating viral variants. Building upon the COBRA technology, nine next-generation H3N2 influenza hemagglutinin (HA) vaccines were designed using a next generation algorithm and design methodology. These next-generation broadly reactive COBRA H3 HA vaccines were superior to wild-type HA vaccines at eliciting antibodies with high HAI activity against a panel of historical and co-circulating H3N2 influenza viruses isolated over the last 15 years, as well as the ability to neutralize future emerging H3N2 isolates.

scholarly journals Broadly Reactive H2 Hemagglutinin Vaccines Elicit Cross-Reactive Antibodies in Ferrets Preimmune to Seasonal Influenza A Viruses

mSphere ◽  
2021 ◽  
Vol 6 (2) ◽  
Author(s):  
Z. Beau Reneer ◽  
Amanda L. Skarlupka ◽  
Parker J. Jamieson ◽  
Ted M. Ross
Keyword(s):  
Influenza Virus ◽  
Immune Responses ◽  
Recombinant Proteins ◽  
Human Population ◽  
Influenza A ◽  
Seasonal Influenza ◽  
Influenza Viruses ◽  
Wild Type ◽  
Influenza A Viruses ◽  
Global Pandemic

ABSTRACT Influenza vaccines have traditionally been tested in naive mice and ferrets. However, humans are first exposed to influenza viruses within the first few years of their lives. Therefore, there is a pressing need to test influenza virus vaccines in animal models that have been previously exposed to influenza viruses before being vaccinated. In this study, previously described H2 computationally optimized broadly reactive antigen (COBRA) hemagglutinin (HA) vaccines (Z1 and Z5) were tested in influenza virus “preimmune” ferret models. Ferrets were infected with historical, seasonal influenza viruses to establish preimmunity. These preimmune ferrets were then vaccinated with either COBRA H2 HA recombinant proteins or wild-type H2 HA recombinant proteins in a prime-boost regimen. A set of naive preimmune or nonpreimmune ferrets were also vaccinated to control for the effects of the multiple different preimmunities. All of the ferrets were then challenged with a swine H2N3 influenza virus. Ferrets with preexisting immune responses influenced recombinant H2 HA-elicited antibodies following vaccination, as measured by hemagglutination inhibition (HAI) and classical neutralization assays. Having both H3N2 and H1N1 immunological memory regardless of the order of exposure significantly decreased viral nasal wash titers and completely protected all ferrets from both morbidity and mortality, including the mock-vaccinated ferrets in the group. While the vast majority of the preimmune ferrets were protected from both morbidity and mortality across all of the different preimmunities, the Z1 COBRA HA-vaccinated ferrets had significantly higher antibody titers and recognized the highest number of H2 influenza viruses in a classical neutralization assay compared to the other H2 HA vaccines. IMPORTANCE H1N1 and H3N2 influenza viruses have cocirculated in the human population since 1977. Nearly every human alive today has antibodies and memory B and T cells against these two subtypes of influenza viruses. H2N2 influenza viruses caused the 1957 global pandemic and people born after 1968 have never been exposed to H2 influenza viruses. It is quite likely that a future H2 influenza virus could transmit within the human population and start a new global pandemic, since the majority of people alive today are immunologically naive to viruses of this subtype. Therefore, an effective vaccine for H2 influenza viruses should be tested in an animal model with previous exposure to influenza viruses that have circulated in humans. Ferrets were infected with historical influenza A viruses to more accurately mimic the immune responses in people who have preexisting immune responses to seasonal influenza viruses. In this study, preimmune ferrets were vaccinated with wild-type (WT) and COBRA H2 recombinant HA proteins in order to examine the effects that preexisting immunity to seasonal human influenza viruses have on the elicitation of broadly cross-reactive antibodies from heterologous vaccination.

scholarly journals Adjuvanted Influenza Vaccines Elicits Higher Antibody Responses against the A(H3N2) Subtype than Non-Adjuvanted Vaccines

Vaccines ◽  
2020 ◽  
Vol 8 (4) ◽  
pp. 704
Author(s):  
Laura Sánchez de Prada ◽  
Iván Sanz Muñoz ◽  
Javier Castrodeza Sanz ◽  
Raúl Ortiz de Lejarazu Leonardo ◽  
José María Eiros Bouza
Keyword(s):  
Influenza Vaccine ◽  
Influenza A ◽  
Seasonal Influenza ◽  
The Elderly ◽  
Antibody Responses ◽  
Serological Response ◽  
Serum Samples ◽  
H3n2 Subtype ◽  
Serological Studies ◽  
Vaccination Campaigns

Background: vaccination is the best approach to prevent influenza infections so far. Serological studies on the effect of different vaccine types are important to address vaccination campaigns and protect our population. In our study, we compared the serological response against influenza A subtypes using the non-adjuvanted influenza vaccine (NAIV) in adults and the elderly and the adjuvanted influenza vaccine (AIV) in the elderly. Methods: We performed a retrospective analysis by hemagglutination inhibition assay (HI) of serum samples right before and 28 days after seasonal influenza vaccination during the 1996–2017 seasons. Conclusions: The AIV presents better performance against the A(H3N2) subtype in the elderly whereas the NAIV induces a better response against A(H1N1)pdm09 in the same group.

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