Efficacy of vaccines against Streptococcus pneumoniae: Difference between revisions
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S. pneumoniae can develop resistance to penicillin via cleavage of penicillin antibiotic by enzyme β-Lactamase or by modifying the penicillin binding proteins (PBPs). β-lactamase works by hydrolyzing and inactivating the drug however, it is exclusively found in staphylococci (Chambers, 1999). Penicillin resistance in S. pneumoniae occurs by alteration of targeted PBPs in the resistant strains. The alterations are caused by mutations in the PBPs, which lower its affinity to bind to penicillin (Slonczewski and Foster, 2009). PBP2x in S. pneumoniae is involved in the development of β-lactam resistance (Laible and Hakenbeck, 1991). Genome sequencing of the penicillin resistant strains shows that point- mutations in PBP2x decreases is affinity to bind to penicillin (Laible and Hakenbeck, 1991). Alteration of PSP target, specifically PBP2x, gives S. pneumoniae resistance to various β-lactam antibiotics like penicillin. | S. pneumoniae can develop resistance to penicillin via cleavage of penicillin antibiotic by enzyme β-Lactamase or by modifying the penicillin binding proteins (PBPs). β-lactamase works by hydrolyzing and inactivating the drug however, it is exclusively found in staphylococci (Chambers, 1999). Penicillin resistance in S. pneumoniae occurs by alteration of targeted PBPs in the resistant strains. The alterations are caused by mutations in the PBPs, which lower its affinity to bind to penicillin (Slonczewski and Foster, 2009). PBP2x in S. pneumoniae is involved in the development of β-lactam resistance (Laible and Hakenbeck, 1991). Genome sequencing of the penicillin resistant strains shows that point- mutations in PBP2x decreases is affinity to bind to penicillin (Laible and Hakenbeck, 1991). Alteration of PSP target, specifically PBP2x, gives S. pneumoniae resistance to various β-lactam antibiotics like penicillin. | ||
== | ==Current pneumococcal vaccines == | ||
< | As outlined above, due to the high β-lactam antibiotic resistance of S. pneumoniae, vaccines have been created that target cell surface polysaccharide and/or proteins. The two vaccines that are widely used are polysaccharide vaccines (23-valent polysaccharide vaccine) and pneumococcal conjugate vaccines (heptavalent protein–polysaccharide conjugate vaccine). | ||
23-valent polysaccharide vaccine. | |||
As the name suggests this vaccine contains capsular polysaccharides for 23 serotypes (1, 2, 3, 4, 5, 6b, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F) (Pletz et. al. 2008). To gain immunity the polysaccharides induce B cell dependant response by releasing polysaccharide Immunoglobulin M (IgM), which are a type of antibodies produced by B cells. However due to an immature immune system polysaccharide vaccines cannot be used on infants <2. | |||
A study done in Mexico evaluating the immune response of this vaccine in children under 5, for 6 serotypes, suggests that the pneumococcal polysaccharide vaccine produced adequate immunogenicity in the given age group (Padilla et. al. 2012). However, this vaccine is not effective in children under 2 years of age (Black et. al. 2000; pedilla et. al. 2012). Therefore, a more comprehensive and a cost effective vaccine is still needed. | |||
Heptavalent protein–polysaccharide conjugate vaccine (PCV-7). | |||
Unlike the 23-valent polysaccharide vaccine, which can only be used in children >2years the conjugate vaccine can be administered to infants as young as 2months old. | |||
Polysaccharides of in this vaccine are from seven serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) that are most frequently involved in infant infections. As the name suggests this vaccine is conjugated to protein (CRM197), which is a non-toxic diphtheria toxoid protein (Pletz et. al. 2008). The protein-specific type 2 T cells associate with B cells, which are bound to the polysaccharide-protein complex via a polysaccharide specific IgM. This association between T and B cells presents the processed protein (CRM197) along with class II MHC (Major Histocompatibility Complex) to the effector T cells (Pletz et. al. 2008). Class II MHCs are cell-surface molecules that mediate interaction between immune cells and body cells. The antigens from Class II peptides come from extracellular proteins instead of from inside the cell. This mechanism leads to adaptive immunity in infants | |||
==Section 3== | ==Section 3== | ||
Revision as of 21:08, 26 March 2013
Introduction
Antibiotic resistance is the decrease in effectiveness of a drug because the sub-population of the microorganism (usually bacteria) being targeted are able to survive exposure to the antibiotic. Antibiotic resistance is a growing concern because antibiotics select for growth of rare microorganisms in a population that is otherwise susceptible to the drug (Slonczewski and Foster, 2009). Bacteria gain antibiotic resistance in various ways, they can pump out the antibiotics through an efflux transmembrane, bypass target pathway, prevent antibiotic from entering the cell and through target mediated Antibacterial Resistance (Slonczewski and Foster, 2009). Streptococcus pneumoniae is a pathogenic, gram-positive, α-hemolytic, anaerobic bacterium that causes pneumonia along with other pneumococcal infections including meningitis, sepsis, cellulitis, bacteremia, septic arthritis, otitis, brain abscess, pericarditis and peritonitis. Mechanisms by which S. pneumoniae develop antibiotic resistance to penicillin (and its derivatives) is essential in the understanding of antibiotic resistance. Such mechanisms can be used to study how newer pathogenic, gram-positive bacteria; similar to S. pneumoniae, might develop antibiotic resistance. Due to increasing rate of antibiotic resistance it is important to study newer ways in which growth of S. pneumoniae can be inhibited. One such way is by targeting highly conserved surface proteins of S. pneumoniae, thereby disabling the bacteria from becoming virulent. This way the bacteria is not killed however, its ability to infect has finished. Subsequently surface proteins that are essentially virulence factors can be used to create vaccines that generate immunogenicity (Jedrzejas, 2007).
Failure of Penicillin antibiotics
Penicillin is a bactericidal drug that functions by inhibiting the formation of peptidoglycan. Peptidolgycan is necessary for cell wall formation; it has two components, glycan and peptide cross-bridges that make up the cell wall. Penicillin blocks cross-bridge formation by targeting transpeptidase that helps in cross-linking the peptides (Slonczewski and Foster, 2009). Penicillin is a β-Lactam antibiotic that consists of a β-Lactam ring in its core structure; the β-Lactam ring is derived by combining cysteine and valine (Slonczewski and Foster, 2009). The molecular structure of Penicillin mimics the D-ala-D-ala cross bridge, which allows it to bind to penicillin binding proteins (transpeptidase and transglycosylase). S. pneumoniae can develop resistance to penicillin via cleavage of penicillin antibiotic by enzyme β-Lactamase or by modifying the penicillin binding proteins (PBPs). β-lactamase works by hydrolyzing and inactivating the drug however, it is exclusively found in staphylococci (Chambers, 1999). Penicillin resistance in S. pneumoniae occurs by alteration of targeted PBPs in the resistant strains. The alterations are caused by mutations in the PBPs, which lower its affinity to bind to penicillin (Slonczewski and Foster, 2009). PBP2x in S. pneumoniae is involved in the development of β-lactam resistance (Laible and Hakenbeck, 1991). Genome sequencing of the penicillin resistant strains shows that point- mutations in PBP2x decreases is affinity to bind to penicillin (Laible and Hakenbeck, 1991). Alteration of PSP target, specifically PBP2x, gives S. pneumoniae resistance to various β-lactam antibiotics like penicillin.
Current pneumococcal vaccines
As outlined above, due to the high β-lactam antibiotic resistance of S. pneumoniae, vaccines have been created that target cell surface polysaccharide and/or proteins. The two vaccines that are widely used are polysaccharide vaccines (23-valent polysaccharide vaccine) and pneumococcal conjugate vaccines (heptavalent protein–polysaccharide conjugate vaccine).
23-valent polysaccharide vaccine.
As the name suggests this vaccine contains capsular polysaccharides for 23 serotypes (1, 2, 3, 4, 5, 6b, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19F, 19A, 20, 22F, 23F and 33F) (Pletz et. al. 2008). To gain immunity the polysaccharides induce B cell dependant response by releasing polysaccharide Immunoglobulin M (IgM), which are a type of antibodies produced by B cells. However due to an immature immune system polysaccharide vaccines cannot be used on infants <2. A study done in Mexico evaluating the immune response of this vaccine in children under 5, for 6 serotypes, suggests that the pneumococcal polysaccharide vaccine produced adequate immunogenicity in the given age group (Padilla et. al. 2012). However, this vaccine is not effective in children under 2 years of age (Black et. al. 2000; pedilla et. al. 2012). Therefore, a more comprehensive and a cost effective vaccine is still needed.
Heptavalent protein–polysaccharide conjugate vaccine (PCV-7).
Unlike the 23-valent polysaccharide vaccine, which can only be used in children >2years the conjugate vaccine can be administered to infants as young as 2months old. Polysaccharides of in this vaccine are from seven serotypes (4, 6B, 9V, 14, 18C, 19F and 23F) that are most frequently involved in infant infections. As the name suggests this vaccine is conjugated to protein (CRM197), which is a non-toxic diphtheria toxoid protein (Pletz et. al. 2008). The protein-specific type 2 T cells associate with B cells, which are bound to the polysaccharide-protein complex via a polysaccharide specific IgM. This association between T and B cells presents the processed protein (CRM197) along with class II MHC (Major Histocompatibility Complex) to the effector T cells (Pletz et. al. 2008). Class II MHCs are cell-surface molecules that mediate interaction between immune cells and body cells. The antigens from Class II peptides come from extracellular proteins instead of from inside the cell. This mechanism leads to adaptive immunity in infants
Section 3
Include some current research in each topic, with at least one figure showing data.
Conclusion
Overall paper length should be 3,000 words, with at least 3 figures.
References
Edited by (your name here), a student of Nora Sullivan in BIOL187S (Microbial Life) in The Keck Science Department of the Claremont Colleges Spring 2013.
