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The 2009 H1N1 influenza virus outbreak is the first pandemic of the twenty-first century. Epidemiological data reveal that of all the people afflicted with H1N1 virus, <5% are over 51 y of age. Interestingly, in the uninfected population, 33% of those >60 y old have pre-existing neutralizing Abs against the 2009 H1N1 virus. This finding suggests that(More)
Most immune responses follow Burnet's rule in that Ag recruits specific lymphocytes from a large repertoire and induces them to proliferate and differentiate into effector cells. However, the phenomenon of "original antigenic sin" stands out as a paradox to Burnet's rule of B cell engagement. Humans, upon infection with a novel influenza strain, produce Abs(More)
Influenza is an important contributor to morbidity and mortality worldwide. Accumulation of genetic mutations termed antigenic drift, allows influenza viruses to inflict yearly epidemics that may result in 250,000 to 500,000 deaths annually. Over 90% of influenza-related deaths occur in the older adult population. This is at least in part a result of(More)
As an attractive alternative to conventional vaccines, DNA vaccines play a critical role in inducing protection against several infectious diseases. In this review, we discuss the advantages that DNA vaccines offer in comparison to conventional protein-based vaccines. We discuss strategies to improve the potency and efficacy of DNA vaccines. Specifically,(More)
The interaction of CD28, which is constitutively expressed on T cells, with B7.1/B7.2 expressed on APCs is critical for T cell activation. CD28 is also expressed on murine and human plasma cells but its function on these cells remains unclear. There are two types of plasma cells: short-lived ones that appear in the secondary lymphoid tissue shortly after Ag(More)
Original antigenic sin is a phenomenon wherein sequential exposure to closely related influenza virus variants reduces antibody (Ab) response to novel antigenic determinants in the second strain and, consequently, impairs the development of immune memory. This could pose a risk to the development of immune memory in persons previously infected with or(More)
Background.  Influenza disproportionately impacts older adults while current vaccines have reduced effectiveness in the older population. Methods.  We conducted a comprehensive evaluation of cellular and humoral immune responses of adults aged 50 years and older to the 2008-2009 seasonal trivalent inactivated influenza vaccine and assessed factors(More)
Myeloid dendritic cells (mDCs) have long been thought to function as classical APCs for T cell responses. However, we demonstrate that influenza viruses induce rapid differentiation of human monocytes into mDCs. Unlike the classic mDCs, the virus-induced mDCs failed to upregulate DC maturation markers and were unable to induce allogeneic(More)
Recognition of pathogen-associated molecular patterns by pattern recognition receptors of the innate immune system is crucial for the initiation of innate and adaptive responses and for immunological memory. We investigated the role of TLR7 in the induction of adaptive immunity and long-term memory following influenza virus infection and vaccination in(More)
Aging is associated with a decline in immune function (immunosenescence) that leads to progressive deterioration in both innate and adaptive immune functions. These changes contribute to the subsequent increased risk for infectious diseases and their sequelae. Vaccination is the most effective and inexpensive public health strategy for prevention of(More)