Comparison of neutralizing antibody and cell-mediated immune responses to pandemic H1N1 2009 influenza virus before and after H1N1 2009 influenza vaccination of elderly subjects and healthcare workers

Hsu, Jung Pu; Phoon, Meng Chee; Koh, Gerald Choon-Huat; Chen, Mark; Lee, Vernon J.; Wu, Yan; Xie, Mingjun; Cheong, Angela; Leo, Yee Sin; Chow, Vincent T. K.

doi:10.1016/j.ijid.2012.04.010

Cited by 22 publications

(23 citation statements)

References 32 publications

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“…Previous studies have indicated that influenza virus-specific CD8 T cells primed by influenza virus infection can be boosted with TIV or LAIV vaccines (43)(44)(45). In our study we investigated if CD8 T cell responses could be primed by TIV vaccination.…”

Section: Discussionmentioning

confidence: 98%

Standard Trivalent Influenza Virus Protein Vaccination Does Not Prime Antibody-Dependent Cellular Cytotoxicity in Macaques

Jegaskanda

Amarasena

Laurie

et al. 2013

J Virol

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Yearly vaccination with the trivalent inactivated influenza vaccine (TIV) is recommended, since current vaccines induce little cross neutralization to divergent influenza strains. Whether the TIV can induce antibody-dependent cellular cytotoxicity (ADCC) responses that can cross-recognize divergent influenza virus strains is unknown. We immunized 6 influenza-naive pigtail macaques twice with the 2011-2012 season TIV and then challenged the macaques, along with 12 control macaques, serially with H1N1 and H3N2 viruses. We measured ADCC responses in plasma to a panel of H1 and H3 hemagglutinin (HA) proteins and influenza virus-specific CD8 T cell (CTL) responses using a sensitive major histocompatibility complex (MHC) tetramer reagent. The TIV was weakly immunogenic and, although binding antibodies were detected by enzyme-linked immunosorbent assay (ELISA), did not induce detectable influenza virus-specific ADCC or CTL responses. The H1N1 challenge elicited robust ADCC to both homologous and heterologous H1 HA proteins, but not influenza virus HA proteins from different subtypes (H2 to H7). There was no anamnestic influenza virus-specific ADCC or CTL response in vaccinated animals. The subsequent H3N2 challenge did not induce or boost ADCC either to H1 HA proteins or to divergent H3 proteins but did boost CTL responses. ADCC or CTL responses were not induced by TIV vaccination in influenza-naive macaques. There was a marked difference in the ability of infection compared to that of vaccination to induce cross-reactive ADCC and CTL responses. Improved vaccination strategies are needed to induce broad-based ADCC immunity to influenza.

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Section: Discussionmentioning

confidence: 98%

Standard Trivalent Influenza Virus Protein Vaccination Does Not Prime Antibody-Dependent Cellular Cytotoxicity in Macaques

Jegaskanda

Amarasena

Laurie

et al. 2013

J Virol

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“…A more rapid decline of specific immunity following vaccination may also account for observations on the questionable efficacy of influenza vaccine in older compared to younger individuals [26, 27], as well as shifts in age distribution towards older individuals following a pandemic, which we already observed in later epidemics of A(H1N1)pdm09 infection in Singapore [6] and elsewhere [7]. If indeed we are unable to maintain a durable humoral immune response to influenza in the elderly, then influenza vaccine development would need to focus on alternative strategies such as stimulation of T-cell responses against influenza, as these may be better preserved than humoral immunity in the elderly [28–30]. In addition, our findings also suggest that symptomatic infections may generate more robust immune responses than asymptomatic infections as indicated by the higher titers observed in the former by both HI and MN.…”

Section: Discussionmentioning

confidence: 99%

Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore

et al. 2014

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BackgroundThe rate of decline of antibody titers to influenza following infection can affect results of serological surveys, and may explain re-infection and recurrent epidemics by the same strain.MethodsWe followed up a cohort who seroconverted on hemagglutination inhibition (HI) antibody titers (≥4-fold increase) to pandemic influenza A(H1N1)pdm09 during a seroincidence study in 2009. Along with the pre-epidemic sample, and the sample from 2009 with the highest HI titer between August and October 2009 (A), two additional blood samples obtained in April 2010 and September 2010 (B and C) were assayed for antibodies to A(H1N1)pdm09 by both HI and virus microneutralization (MN) assays. We analyzed pair-wise mean-fold change in titers and the proportion with HI titers ≥ 40 and MN ≥ 160 (which correlated with a HI titer of 40 in our assays) at the 3 time-points following seroconversion.ResultsA total of 67 participants contributed 3 samples each. From the highest HI titer in 2009 to the last sample in 2010, 2 participants showed increase in titers (by HI and MN), while 63 (94%) and 49 (73%) had reduction in HI and MN titers, respectively. Titers by both assays decreased significantly; while 70.8% and 72.3% of subjects had titers of ≥ 40 and ≥ 160 by HI and MN in 2009, these percentages decreased to 13.9% and 36.9% by September 2010. In 6 participants aged 55 years and older, the decrease was significantly greater than in those aged below 55, so that none of the elderly had HI titers ≥ 40 nor MN titers ≥ 160 by the final sample. Due to this decline in titers, only 23 (35%) of the 65 participants who seroconverted on HI in sample A were found to seroconvert between the pre-epidemic sample and sample C, compared to 53 (90%) of the 59 who seroconverted on MN on Sample A.ConclusionsWe observed marked reduction in titers 1 year after seroconversion by HI, and to a lesser extent by MN. Our findings have implications for re-infections, recurrent epidemics, vaccination strategies, and for cohort studies measuring infection rates by seroconversion.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-414) contains supplementary material, which is available to authorized users.

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“…Although assessment of antibody responses to influenza vaccines is mainly used as a measure of efficacy, studies continue to show that humoral immunity by itself does not provide sterilizing immunity against infection in older adults, and that T-cell responses are critically important when antibody-mediated protection fails (81). Furthermore, T-cell responses are cross-reactive within the strains of influenza A or influenza B, allowing for broad protection against drifted strains of influenza (82).…”

Section: The Role Of T-cells In Influenza Infection and Vaccinationmentioning

confidence: 99%

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

et al. 2017

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The number of people over the age of 60 is expected to double by 2050 according to the WHO. This emphasizes the need to ensure optimized resilience to health stressors in late life. In older adults, influenza is one of the leading causes of catastrophic disability (defined as the loss of independence in daily living and self-care activities). Influenza vaccination is generally perceived to be less protective in older adults, with some studies suggesting that the humoral immune response to the vaccine is further impaired in cytomegalovirus (CMV)-seropositive older people. CMV is a β-herpes virus infection that is generally asymptomatic in healthy individuals. The majority of older adults possess serum antibodies against the virus indicating latent infection. Age-related changes in T-cell-mediated immunity are augmented by CMV infection and may be associated with more serious complications of influenza infection. This review focuses on the impact of aging and CMV on immune cell function, the response to influenza infection and vaccination, and how the current understanding of aging and CMV can be used to design a more effective influenza vaccine for older adults. It is anticipated that efforts in this field will address the public health need for improved protection against influenza in older adults, particularly with regard to the serious complications leading to loss of independence.

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Comparison of neutralizing antibody and cell-mediated immune responses to pandemic H1N1 2009 influenza virus before and after H1N1 2009 influenza vaccination of elderly subjects and healthcare workers

Cited by 22 publications

References 32 publications

Standard Trivalent Influenza Virus Protein Vaccination Does Not Prime Antibody-Dependent Cellular Cytotoxicity in Macaques

Standard Trivalent Influenza Virus Protein Vaccination Does Not Prime Antibody-Dependent Cellular Cytotoxicity in Macaques

Rate of decline of antibody titers to pandemic influenza A (H1N1-2009) by hemagglutination inhibition and virus microneutralization assays in a cohort of seroconverting adults in Singapore

Impact of Aging and Cytomegalovirus on Immunological Response to Influenza Vaccination and Infection

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