Cancer and immunization (thread)

[Rich66]

1: Cancer Immunol Immunother. 2009 Dec;58(12):1949-57. Epub 2009 May 15. Links

Use of CD40L immunoconjugates to overcome the defective immune response to vaccines for infections and cancer in the aged.

Tang YC, Thoman M, Linton PJ, Deisseroth A.
Sidney Kimmel Cancer Center, San Diego, CA 92121, USA.
Multiple investigators have reported the presence of defects in the immune response of the elderly [Castle In: Clin Infect Dis 31:578, 2000; Ortqvist et al. In: Eur Respir J 30:414-422, 2007; Saurwein-Teissl et al. In: J Immunol 168:5893, 2002; Haynes et al. In: Proc Natl Acad Sci USA 100:15053-15058, 2003]. These defects reduce the magnitude of the immune response to infection and to vaccination. In individuals greater than 55 years of age, the probability of developing a fully protective neutralizing antibody response to the yearly multivalent particle inactivated influenza vaccine is less than 20% [Jefferson et al. In: Lancet 264:1165-1174, 2005; Goodwin et al. In: Vaccine 24:1159-1169, 2006; Jackson et al. In: Lancet 372:398-405, 2008; Simonsen and Taylor In: Lancet 7:658-666, 2007]. The defects in the aged immune system that are responsible for this limited response to vaccination in the older age groups include functional defects of the antigen presenting cells, functional defects in CD4 helper CD4 T cells and monocytes, and an altered microenvironment [Eaton et al. In: J Exp Med 200:1613-1622, 2004; Dong et al. In: J Gen Virol 84:1623-1628, 2003; Deng et al. In: Immunology 172:3437-3446, 2004; Cella et al. In: J Exp Med 184:747-752, 1996]. Starting at puberty, the involution of the thymus and the consequent reduction of the export of naïve T cells specific to neo-antigens leads to the reduction of the ratio of antigen naïve to memory cells as chronological age advances [Prelog In: Autoimmun Rev 5:136-139, 2006; McElhaney et al. In: J Immunology 176:6333-6339, 2006]. Changes in glycosylation of T cells and target antigens acquired during the aging process and the antibodies to these new glycopeptides and glycoproteins may also contribute to a reduction in the functioning of the adaptive immune response [Ishii et al. In: J Clin Neurosci 14:110-115, 2007; Shirai et al. In: Clin Exp Immunol 12:455-464, 1972; Adkins and Riley In: Mech Ageing Dev 103:147-164, 1998; Ben-Yehuda and Weksler In: Cancer Investigation 10:525-531, 1992]. One of the more interesting examples of the functional defects in the cells of the adaptive immune response is a reduced level of expression in the surface cytoadhesion and activation receptor molecules on CD4 helper T cells undergoing activation during vaccination. Upon infection or vaccination, CD40L is typically increased on the surface of CD4 helper T cells during activation, and this increased expression is absolutely essential to the CD40L promotion of expansion of antigen-specific B cells and CD 8 effector T cells in response to infection or vaccination [Singh et al. In: Protein Sci 7:1124-1135, 1998; Grewal and Flavell In: Immunol Res 16: 59-70, 1997; Kornbluth In: J Hematother Stem Cell Res 11:787-801, 2002; Garcia de Vinuesa et al. In: Eur J Immunol 29:3216-3224, 1999]. In aged human beings and mice, the reduced levels of expression of CD40 ligand (CD40L) in activated CD4 helper T cells is dramatically reduced [Eaton et al. In: J Exp Med 200:1613-1622, 2004; Dong et al. In: J Gen Virol 84:1623-1628, 2003]. To circumvent the reduction in CD40L expression and the subsequent reduction in immune response in the elderly, we have developed a chimeric vaccine comprised of the CD40L linked to the target antigen, in a replication incompetent adenoviral vector and in booster protein. This review will discuss the implementation the potential use of this approach for the vaccination of the older populations for cancer and infection.
PMID: 19444444 [PubMed - in process

12/28/09
High dose seasonal flu vaccine approved by FDA:
http://www.medscape.com/viewarticle/...e&uac=124502MT

[Rich66]

Bacterial Coinfection May Have Contributed to H1N1 Deaths

Laurie Barclay, MD
September 30, 2009 — Bacterial coinfection with Streptococcus pneumoniae may have contributed to deaths in the United States from 2009 H1N1 influenza, according to the results of a study reported online first in the September 29 issue of the Morbidity and Mortality Weekly Report. The Centers for Disease Control and Prevention (CDC) are therefore urging pneumococcal vaccination when indicated.
"Our influenza season is off to a fast start and unfortunately there will be more cases of bacterial infections in people suffering from influenza," CDC Epidemiologist Matthew Moore, MD, said in a news release. "It's really important for people, especially those at high risk for the serious complications from influenza, to check with their provider when they get their influenza vaccine about being vaccinated against pneumococcus."
In an analysis of lung tissue specimens from 77 confirmed fatal US cases of 2009 H1N1, in which deaths occurred from May 1 to August 20, 2009, bacterial coinfections were present in 22 (29%) cases. These fatal cases were defined as influenza-like illness or postmortem findings suggesting viral pneumonia and laboratory-confirmed 2009 pandemic influenza A (H1N1) virus infection by real time reverse transcriptase–polymerase chain reaction.
Of the 22 cases with bacterial coinfection, 10 were caused by S pneumoniae, 7 by S aureus, 6 by S pyogenes, 2 by S mitis, and 1 by Haemophilus influenzae. In 4 cases, there were multiple pathogens. Median age was 31 years (range, 2 months – 56 years), and half were men. The cases were reported from California, Hawaii, Illinois, New Jersey, New York, Texas, Utah, and Virginia.
Of the 21 patients with known previous medical history, 16 had underlying medical conditions associated with increased risk for influenza-associated complications, and 15 had indications for vaccination with 23-valent pneumococcal polysaccharide vaccine.
The CDC is recommending that:

• pneumococcal conjugate vaccine be given to all children younger than 5 years, as per current guidelines, and
• all persons aged 65 years and older, as well as those aged 2 to 64 years with high-risk conditions, receive the 23-valent pneumococcal polysaccharide vaccine, as described on the CDC's Web site.

Limitations of this report are that the cases do not come from a systematic sample and might not be representative of all pandemic H1N1 deaths or all pandemic H1N1 deaths associated with bacterial pneumonia. Not all potential bacterial pathogens were evaluated, patient information was limited, and evaluation of bacterial coinfections was performed at autopsy.
"The findings in this report also underscore the importance of managing patients with influenza who also might have bacterial pneumonia with both empiric antibacterial therapy and antiviral medications," the editors conclude. "In addition, public health departments should encourage the use of pneumococcal vaccine, seasonal influenza vaccine, and, when the vaccine becomes available, pandemic influenza A (H1N1) 2009 monovalent vaccine."