scholarly journals Age-specific differences in the dynamics of protective immunity to influenza

2018 ◽  
Author(s):  
Sylvia Ranjeva ◽  
Rahul Subramanian ◽  
Vicky J. Fang ◽  
Gabriel M. Leung ◽  
Dennis K. M. Ip ◽  
...  

AbstractInfluenza A viruses evolve rapidly to escape host immunity, such that individuals can be infected multiple times with the same subtype. The form and duration of protective immunity after each influenza infection are poorly understood. Here, we quantify the dynamics of protective immunity against influenza A virus infections by fitting individual-level mechanistic models to longitudinal serology from children and adults in a household cohort study. We find that most protection in children is explained by antibody titers measured by the hemagglutination inhibition (HI) assay. In contrast, in adults, HI antibody titers explain a smaller fraction of protection. Protection against circulating strains wanes to approximately 50% of peak levels 3.5-7 years after infection in both age groups, and wanes faster against influenza A(H3N2) than A(H1N1)pdm09. Protection against H3N2 lasts longer in adults than in children. Our results suggest that the focus of influenza antibody responses changes over time from the highly mutable hemagglutinin head to other epitopes, consistent with the immunological theory of original antigenic sin, and that this change of focus might affect protection. Additionally, we estimate that imprinting, or primary infection with a subtype of one phylogenetic group, has little to no effect on the risk of non-medically attended influenza infections in adults. We also find no evidence of long-term cross-protection between subtypes. This work underscores the need for longitudinal data on multiple components of the immune response to better understand the development of immunity and differences in susceptibility within populations.


2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Maryrose R. Laguio-Vila ◽  
Mark G. Thompson ◽  
Sue Reynolds ◽  
Sarah M. Spencer ◽  
Manjusha Gaglani ◽  
...  

Abstract Background.  Most inactivated influenza vaccines contain purified and standardized hemagglutinin (HA) and residual neuraminidase (NA) antigens. Vaccine-associated HA antibody responses (hemagglutination inhibition [HAI]) are well described, but less is known about the immune response to the NA. Methods.  Serum of 1349 healthcare personnel (HCP) electing or declining the 2010–2011 trivalent-inactivated influenza vaccine ([IIV3], containing A/California/7/2009 p(H1N1), A/Perth/16/2009 [H3N2], B/Brisbane/60/2008 strains) were tested for NA-inhibiting (NAI) antibody by a modified lectin-based assay using pseudotyped N1 and N2 influenza A viruses with an irrelevant (H5) HA. Neuraminidase-inhibiting and HAI antibody titers were evaluated approximately 30 days after vaccination and end-of-season for those with polymerase chain reaction (PCR)-confirmed influenza infection. Results.  In 916 HCP (68%) receiving IIV3, a 2-fold increase in N1 and N2 NAI antibody occurred in 63.7% and 47.3%, respectively. Smaller responses occurred in HCP age >50 years and those without prior 2009–2010 IIV3 nor monovalent A(H1N1)pdm09 influenza vaccinations. Forty-four PCR-confirmed influenza infections were observed, primarily affecting those with lower pre-exposure HAI and NAI antibodies. Higher pre-NAI titers correlated with shorter duration of illness for A(H1N1)pdm09 virus infections. Conclusions.  Trivalent-inactivated influenza vaccine is modestly immunogenic for N1 and N2 antigens in HCP. Vaccines eliciting robust NA immune responses may improve efficacy and reduce influenza-associated morbidity.



1986 ◽  
Vol 96 (3) ◽  
pp. 513-522 ◽  
Author(s):  
Walter E. P. Beyer ◽  
Jos T. M. Van Der Logt ◽  
Ruud van Beek ◽  
Nic Masurel

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.



1985 ◽  
Vol 95 (2) ◽  
pp. 437-445 ◽  
Author(s):  
R. Pyhälä

SUMMARYThe incidence of haemagglutination inhibition (HI) antibody (titre ≥ 12) to influenza A/Singapore/1/57(H2N2) in sera collected from a Finnish population in the summer of 1981 was 58%. Subjects born after 1968 were essentially seronegative, and a comparable low HI antibody status was also recorded among the elderly, lowest being in people born during the period 1901–10. A small increase in antibody titre to the H2N2 virus was observed in the different age groups after infections with the H3N2, but not the H1N1, subtype influenza A viruses. The heterotypic response, which could be due to HI or NA antibodies, was restricted almost exclusively to subjects already exhibiting this antibody in acute phase sera. Moreover, the anamnestic boosting was not as strong as that described in earlier studies from samples collected at the beginning of the present era of H3N2 viruses.At population level, the HI antibody status to H2N2 was about the same at the beginning and end of the follow-up period which covered eight epidemic seasons. The results are discussed with respect to the doctrine of ‘original antigenic sin’ and to the threat of re-emergence of the H2N2 viruses.



2021 ◽  
Vol 52 (1) ◽  
Author(s):  
Juliana Bonin Ferreira ◽  
Zvonimir Poljak ◽  
Robert Friendship ◽  
Éva Nagy ◽  
Greg Wideman ◽  
...  

AbstractInfluenza A viruses (IAVs) are common causes of respiratory infection in pigs. The objective of this study was to characterize the circulation of IAVs between weaning and market age on the basis of development of antibody response and molecular epidemiology of detected viruses. Two batches of weaned pigs were followed in the nursery and finisher barns with a sample of 81 and 75 pigs. Nasal swabs and blood samples were collected from individual pigs for virological and serological analyses. A H3N2 subtype virus, of cluster IV, was detected in Study 1, with a maximum of 97.9% identity to HA gene of viruses previously isolated in Ontario. In Study 2, a H1N1 subtype virus, of 2009 H1N1 pandemic lineage, was detected, with a maximum of 97.8% identity to HA gene of viruses previously isolated in Ontario. On the basis of HA gene, it was observed that pigs were being detected with the same virus over time. The existence of antibody titers for IAV other than the isolated one confirmed that more than one subtype can circulate in the same population. In Study 1, pigs with higher numbers of IAV detection had lower serological titers for the same virus that was confirmed to circulate in the nursery (P < 0.01). Thorough knowledge of all endemic viral strains is fundamental for development of infection and disease control, particularly in complex production systems. This may include consideration of sampling and testing strategies which could detect circulation of all IAV variants, even if they have low prevalence.



2014 ◽  
Vol 56 (3) ◽  
pp. 191-195
Author(s):  
Dalva Assunção Portari Mancini ◽  
Aparecida Santo Pietro Pereira ◽  
Rita Maria Zucatelli Mendonça ◽  
Adelia Hiroko Nagamori Kawamoto ◽  
Rosely Cabette Barbosa Alves ◽  
...  

Equines are susceptible to respiratory viruses such as influenza and parainfluenza. Respiratory diseases have adversely impacted economies all over the world. This study was intended to determine the presence of influenza and parainfluenza viruses in unvaccinated horses from some regions of the state of São Paulo, Brazil. Blood serum collected from 72 equines of different towns in this state was tested by hemagglutination inhibition test to detect antibodies for both viruses using the corresponding antigens. About 98.6% (71) and 97.2% (70) of the equines responded with antibody protective titers (≥ 80 HIU/25µL) H7N7 and H3N8 subtypes of influenza A viruses, respectively. All horses (72) also responded with protective titers (≥ 80) HIU/25µL against the parainfluenza virus. The difference between mean antibody titers to H7N7 and H3N8 subtypes of influenza A viruses was not statistically significant (p > 0.05). The mean titers for influenza and parainfluenza viruses, on the other hand, showed a statistically significant difference (p < 0.001). These results indicate a better antibody response from equines to parainfluenza 3 virus than to the equine influenza viruses. No statistically significant differences in the responses against H7N7 and H3N8 subtypes of influenza A and parainfluenza 3 viruses were observed according to the gender (female, male) or the age (≤ 2 to 20 years-old) groups. This study provides evidence of the concomitant presence of two subtypes of the equine influenza A (H7N7 and H3N8) viruses and the parainfluenza 3 virus in equines in Brazil. Thus, it is advisable to vaccinate equines against these respiratory viruses.



2005 ◽  
Vol 79 (15) ◽  
pp. 9926-9932 ◽  
Author(s):  
Kyoko Shinya ◽  
Masato Hatta ◽  
Shinya Yamada ◽  
Ayato Takada ◽  
Shinji Watanabe ◽  
...  

ABSTRACT In 2003, H5N1 avian influenza virus infections were diagnosed in two Hong Kong residents who had visited the Fujian province in mainland China, affording us the opportunity to characterize one of the viral isolates, A/Hong Kong/213/03 (HK213; H5N1). In contrast to H5N1 viruses isolated from humans during the 1997 outbreak in Hong Kong, HK213 retained several features of aquatic bird viruses, including the lack of a deletion in the neuraminidase stalk and the absence of additional oligosaccharide chains at the globular head of the hemagglutinin molecule. It demonstrated weak pathogenicity in mice and ferrets but caused lethal infection in chickens. The original isolate failed to produce disease in ducks but became more pathogenic after five passages. Taken together, these findings portray the HK213 isolate as an aquatic avian influenza A virus without the molecular changes associated with the replication of H5N1 avian viruses in land-based poultry such as chickens. This case challenges the view that adaptation to land-based poultry is a prerequisite for the replication of aquatic avian influenza A viruses in humans.



2019 ◽  
Vol 93 (11) ◽  
Author(s):  
Jurre Y. Siegers ◽  
Marco W. G. van de Bildt ◽  
Zhanmin Lin ◽  
Lonneke M. Leijten ◽  
Rémon A. M. Lavrijssen ◽  
...  

ABSTRACTCentral nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections. Remarkably, zoonotic H5N1 virus infections are more frequently associated with CNS disease than seasonal or pandemic influenza viruses. Little is known about the interaction between influenza A viruses and cells of the CNS; therefore, it is currently unknown which viral factors are important for efficient replication. Here, we determined the replication kinetics of a seasonal, pandemic, zoonotic, and lab-adapted influenza A virus in human neuron-like (SK-N-SH) and astrocyte-like (U87-MG) cells and primary mouse cortex neurons. In general, highly pathogenic avian influenza (HPAI) H5N1 virus replicated most efficiently in all cells, which was associated with efficient attachment and infection. Seasonal H3N2 and to a lesser extent pandemic H1N1 virus replicated in a trypsin-dependent manner in SK-N-SH but not in U87-MG cells. In the absence of trypsin, only HPAI H5N1 and WSN viruses replicated. Removal of the multibasic cleavage site (MBCS) from HPAI H5N1 virus attenuated, but did not abrogate, replication. Taken together, our results showed that the MBCS and, to a lesser extent, the ability to attach are important determinants for efficient replication of HPAI H5N1 virus in cells of the CNS. This suggests that both an alternative hemagglutinin (HA) cleavage mechanism and preference for α-2,3-linked sialic acids allowing efficient attachment contribute to the ability of influenza A viruses to replicate efficiently in cells of the CNS. This study further improves our knowledge on potential viral factors important for the neurotropic potential of influenza A viruses.IMPORTANCECentral nervous system (CNS) disease is one of the most common extrarespiratory tract complications of influenza A virus infections, and the frequency and severity differ between seasonal, pandemic, and zoonotic influenza viruses. However, little is known about the interaction of these viruses with cells of the CNS. Differences among seasonal, pandemic, and zoonotic influenza viruses in replication efficacy in CNS cells,in vitro, suggest that the presence of an alternative HA cleavage mechanism and ability to attach are important viral factors. Identifying these viral factors and detailed knowledge of the interaction between influenza virus and CNS cells are important to prevent and treat this potentially lethal CNS disease.



Author(s):  
Hannah E Maier ◽  
Guillermina Kuan ◽  
Lionel Gresh ◽  
Roger Lopez ◽  
Nery Sanchez ◽  
...  

Abstract Background Obesity has been shown to increase the risk of severe outcomes and death for influenza virus infections. However, we do not understand the influence of obesity on susceptibility to infection or on nonsevere influenza outcomes. Methods We performed a case-ascertained, community-based study of influenza transmission within households in Nicaragua. To investigate whether obesity increases the likelihood of influenza infection and symptomatic infection we used logistic regression models. Results Between 2015 and 2018, a total of 335 index cases with influenza A and 1506 of their household contacts were enrolled. Obesity was associated with increased susceptibility to symptomatic H1N1pdm infection among adults (odds ratio [OR], 2.10; 95% confidence interval [CI], 1.08–4.06) but not children, and this association increased with age. Among adults with H1N1pdm infection, obesity was associated with increased likelihood of symptoms (OR, 3.91; 95% CI, 1.55–9.87). For middle-aged and older adults with obesity there was also a slight increase in susceptibility to any H1N1pdm infection (OR, 1.20; 95% CI, .62–2.34). Body mass index (BMI) was also linearly associated with increased susceptibility to symptomatic H1N1pdm infection, primarily among middle-aged and older women (5-unit BMI increase OR, 1.40; 95% CI, 1.00–1.97). Obesity was not associated with increased H3N2 susceptibility or associated symptoms. Conclusions We found that, among adults, obesity is associated with susceptibility to H1N1pdm infection and with symptoms associated with H1N1pdm infection, but not with susceptibility to H3N2 infection or associated symptoms. These findings will help target prevention efforts and therapeutics to this high-risk population.



Virology ◽  
2015 ◽  
Vol 476 ◽  
pp. 189-195 ◽  
Author(s):  
Han Lei ◽  
Xiaojue Peng ◽  
Daxian Zhao ◽  
Jiexiu Ouyang ◽  
Huifeng Jiao ◽  
...  


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