NmVac4-A/C/Y/W-135

NmVac4-A/C/Y/W-135
Vaccine description
Target disease Neisseria meningitidis A,C,Y,W-135
Type Subunit
Clinical data
Pregnancy
category
  • US: C (Risk not ruled out)
Routes of
administration		 Intramuscular(IM)
ATC code J07AH04 (WHO)
Identifiers
ChemSpider none
 NYesY (what is this?)  (verify)

NmVac4-A/C/Y/W-135 is the commercial name of the Meningococcal meningitis polysaccharide serogroups A,C,Y and W-135 vaccine of JN-International Medical Corporation. The product is specially designed and formulated to be used in developing countries for protecting populations during meningitis disease epidemics. Meningococcal meningitis is a bacterial infection caused by the bacterium Neisseria meningitidis, also known as meningococcus. The vaccine is made from bacterial capsular polysaccharides through fermentation of each individual serogroup of Neisseria meningitidis in bioreactors. Then the polysaccharides are purified, formulated and lyophilized using preservatives and stabilizers to make a vaccine product. The vaccine cannot protect other than Neisseria meningitidis serogroups A,C,Y and W-135 or cannot completely protect from these serogroups.

History

Since 1995, Dr. Jeeri R Reddy in an association with Institut Pasteur collected more than 800 serotypes of Neisseria meningitidis bacteria from sub-Saharan Africa and tested them for the production of meningitis vaccine. Dr. Reddy selected a few serotypes that those are suitable for production of vaccine against meningitis disease.

The methods of manufacture of the vaccine product is now patented in the United States (USPTO) and in the WIPO Patent Cooperation Treaty (PCT) countries.

Multicenter clinical trials and efficacy

The efficacy of the vaccine was tested in sub-Saharan Africa (Niger and Burkina Faso) using 750 people for a period of 52 weeks (Phase III trials). Protective sero-conversion successfully occurred and protection was tested and recorded in vaccinated individuals during a spontaneous disease outbreak. However, it is well known that this type of vaccine (pure polysaccharides) gives disease protection for no more than 18 months.

Practicality of meningococcal polysaccharide vaccines for epidemics

Limited vaccine supply threatens response to meningitis epidemics in Africa every year during the seasonal disease epidemic. The shortage of vaccine is manmade due to unimproved production capabilities and lack of appropriation of charitable funds. Due to lack of appropriate vaccine stock to prevent the killer disease, World Health Organization is asking vaccine manufacturers about the usage of lower dose for upcoming Meningitis disease outbreak season (2008–2009) - Science, December, 2008 and ScienceDaily (Dec. 6, 2008). Saudi Arabian health authorities have reported a total of 225 cases, including 57 deaths during the Hajj pilgrimage to Mecca. Meningococcal meningitis vaccine containing serogroups A, C, Y, W-135 is currently required by Saudi Arabia for pilgrims visiting Mecca for the Hajj or for the Umrah.[1] Moreover, developing countries are not immune to this disease because morbidity and mortality rates from the disease in developing countries are often higher (20–40%) than in developed countries. Among those who survive the meningococcal disease, 10–20% experience neurological sequelae.[2][3] JN-International Medical Corporation in Ivory Coast has provided over 5 million doses of serotypes A & C vaccine on long term credit to the Ministry of Health of Niger, Burkina Faso, Benin and Ivory Coast during meningitis disease outbreak seasons since the year 2006.

Medical uses

Primary vaccination to children

Children 2–10 years of age who are at high risk for meningococcal disease such as certain chronic medical conditions and travel to or reside in countries with hyperendemic or epidemic meningococcal disease should receive primary immunization. Although safety and efficacy of the vaccine have not been established in children younger than 2 years of age and under outbreak control, the unconjugated vaccine can be considered. Safety and efficacy of NMVAC-4 have not been established in children younger than 11 years of age; however, clinical studies in children 2–10 years of age have been recommended.[4][5][6][7]

Adolescents 11 years of age or older

It is recommend that primary immunization against meningococcal disease with NMVAC-4 for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although NMVAC-4 is the preferred meningococcal vaccine in adolescents 11 years of age or older, NmVac-4 is an acceptable alternative if the conjugated vaccine is unavailable.[5][6][8]

Adults

College Students who plan to live in dormitories receive primary immunization with NMVAC-4. Although the risk for meningococcal disease for is similar to 18–24 years of age that for the general population of similar age. The college students consider vaccination against meningococcal disease to reduce their risk for the disease and stated that college health-care providers should take a proactive role in providing information about meningococcal disease to students and their parents.[9] Although NMVAC-4 is the preferred meningococcal vaccine in adults 55 years of age or younger, NmVac-4 is an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. Since safety and efficacy of NMVAC-4 in adults older than 55 years of age have not been established to date, NmVac-4 should be used for primary immunization in this group.[5][6]

Medical staff and laboratory personnel

Health care people should receive routine immunization against meningococcal disease for laboratory personnel who are routinely exposed to isolates of N. meningitidis. Laboratory personnel and medical staff are at risk of exposure to N. meningitidis or to patients with meningococcal disease. Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations regarding immunization of health-care workers that routine vaccination of health-care personnel is recommended, Any individual 11–55 years of age who wishes to reduce their risk of meningococcal disease may receive NMVAC-4 and those older than 55 years of age. Under certain circumstances if unvaccinated health-care personnel cannot get vaccinated and who have intensive contact with oropharyngeal secretions of infected patients and who do not use proper precautions should receive anti-infective prophylaxis against meningococcal infection (i.e., 2-day regimen of oral rifampin or a single dose of IM ceftriaxone or a single dose of oral ciprofloxacin).[5][10]

Military recruits

Because the risk of meningococcal disease is increased among military recruits, all military recruits routinely receive primary immunization against the disease.[11]

Travelers

It is unfortunate that immunization against meningococcal disease is not a requirement for entry into any country, unlike Yellow fever. Only Saudi Arabia require that travelers to their country for the annual Hajj and Umrah pilgrimage have a certificate of vaccination against meningococcal disease issued not more than 3 years and not less than 10 days before arrival in Saudi Arabia. Travelers to or residents of areas where N. meningitidis is highly endemic or epidemic are at risk of exposure should receive primary immunization against meningococcal disease.[5][6] Peaks of meningococcal disease (usually caused by serogroup A or C) occur regularly during the dry season (i.e., December through June) in that portion of sub-Saharan Africa known as the " meningitis belt," which extends from Mali to Ethiopia. In addition, major epidemics occur every 8–12 years. Travelers to these high-risk areas may be at risk of meningococcal disease and many of these countries do not have established means for surveillance and timely reporting of epidemics [5][12]

HIV-infected individuals

HIV-infected individuals are likely to be at increased risk for meningococcal disease; HIV-infected individuals who wish to reduce their risk of meningococcal disease may receive primary immunization against meningococcal disease.[10] Although efficacy of NMVAC-4 has not been evaluated in HIV-infected individuals to date, HIV-infected individuals 11–55 years of age may receive primary immunization with the conjugated vaccine.[10] Vaccination against meningitis do not decrease CD4+ T-cell counts or increase viral load in HIV-infected individuals and there has been no evidence that the vaccines adversely affect survival.[13][14][15]

Household and close contacts of individuals with invasive meningococcal disease

Protective levels of anticapsular antibodies are not achieved until 7–14 days following administration of a meningococcal vaccine, vaccination cannot prevent early onset disease in these contacts and usually is not recommended following sporadic cases of invasive meningococcal disease.

Disease outbreak control

NMVAC-4 can be used for large-scale vaccination programs when an outbreak of meningococcal disease occurs in Africa and other regions of the world. Whenever sporadic or cluster cases or outbreaks of meningococcal disease occur in the US, chemoprophylaxis is the principal means of preventing secondary cases in household and other close contacts of individuals with invasive disease. NMVAC-4 rarely may be used as an adjunct to chemoprophylaxis,1 but only in situations where there is an ongoing risk of exposure (e.g., when cluster cases or outbreaks occur) and when a serogroup contained in the vaccine is involved. It is important that clinicians promptly report all cases of suspected or confirmed meningococcal disease to local public health authorities and that the serogroup of the meningococcal strain involved be identified. The effectiveness of mass vaccination programs depends on early and accurate recognition of outbreaks. When a suspected outbreak of meningococcal disease occurs, public health authorities will then determine whether mass vaccinations (with or without mass chemoprophylaxis) is indicated and delineate the target population to be vaccinated based on risk assessment.[5]

Contradictions

The safety of the vaccine in pregnant women has not been established. People with component deficiencies in the final common complement pathway (C3,C5-C9) are more susceptible to N. meningitidis infection than complement-satisfactory people,[16][17][18][19][20][21][22] and it was estimated that the risk of infection is 7000 times higher in such individuals.[17] In addition, complement component-deficient population frequently experience frequent meningococcal disease,[23] since their immune response to natural infection may be less complete than that of complement none-deficient people.[16][24] Inherited properdin deficiency also is related with an increased risk of contracting meningococcal disease.[24][16] Because people with functional or anatomic asplenia may not immune to efficiently clear encapsulated Neisseria meningitidis from the bloodstream.[24][16] Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningitis disease.[25][26] The safety of this vaccine in the people with Chronic Medical Conditions has not been established.

Pharmacodynamics

The capsular polysaccharides of Neisseria meningitidis are attractive vaccine candidates because they constitute the most highly conserved and most exposed bacterial-surface antigens.[27] The use of capsular polysaccharides as immunoprophylactic agents against human disease caused by encapsulated bacteria is now firmly established. The capsular polysaccharides of the meningococcus are negatively charged and are obtained in a high molecular weight immunogenic form by precipitation. Meningococcal polysaccharide vaccines are efficacious to protect from meningitis disease in adults,[28][29] but cannot provide full protection to infants under the age of 5.[30] The duration of protection elicited by the meningococcal polysaccharide vaccines is not long lasting in adults and children above four years of age.[31][32][33] For children from one to four years old the duration of protection is less than three years.[30] Protective immunity to encapsulated bacterial pathogens such as N. meningitidis is principally mediated by the reaction between antibody and capsular polysaccharide epitopes. In encapsulated gram negative bacteria, protection results primarily from a direct complement-mediated bactericidal effect.[34] Vaccines have been prepared from the capsular polysaccharides of Neisseria meningitidis (groups A, C, W-135, and Y). These and other polysaccharides have been classified as T cell independent type 2 (TI-2) antigens based on their inability to stimulate an immune response in animals that carry an X-linked immune B-cell defect (xid).[35] TI-2 antigens tend to be characterized by high molecular weight, multiple repeat epitopes, slow degradation in vivo, and a failure to stimulate major histocompatibility complex (MHC) type II mediated T-cell help.[35] TI-2 antigens generally are incapable of stimulating an immune response in neonatal humans under 18 months of age. This has spurred attempts to modify the capsular polysaccharides such that vaccines protective for all at-risk groups will result. To date, the most successful approach has been to covalently bind carrier proteins to the polysaccharides, thus engendering a vaccine capable of invoking a T-dependent response.[36]

Formulation

The vaccine contains 50 mcg of polysaccharide for each of the serogroup's (A, C, Y and W135) purified polysaccharide in a lyophilized form. Active Pharmaceutical Ingredient (API) of C, Y and W-135 serogroups is Sialic acid. Phosphate is an API for serogroup A. Lactose is used as a stabilizer. As a precautionary measure mercury is not used in the vaccine formulation. The vaccine comes in 10 and 50-dose vials and is reconstituted using saline diluent.

Structures of the Capsular Polysaccharides of N. meningitidis A.C.Y and W-135:[37][38]

Group Structure of repeating unit (Fig. 1- Fig. 4)
A →6)α-D-ManNAc(1-PO4→ 3 ↑ OAc
C →9)α-D-NeuNAc(2→ 7/8 ↑ OAc
Y →6)α-D-Glc (l→4) α-D-NeuNAc (2→ (OAc)
W135 →6)α-D-Gal (l→4) α-D-NeuNAc (2→

NMR analysis showed that the structures of the Polysaccharides of N. meningitidis A.C.Y and W-135 isolates collected from Africa and used in the vaccine production are O-acetylation positive (O Ac +) and it is one of the requirement of International Conference on Harmonization ICH and WHO Guidance. O-acetylated polysaccharides influence the immunogenicity of meningococcal vaccines. It is well known that O acetylated at carbon 3 in serogroup A polysaccharide induces higher Serum Bactericidal Antibody (SBA) detectable anti- serogroup A antibodies in human. Serogroups C, W-135, and Y also have various degrees of O-acetylation, whereas, none O-acetylated of these serogroups can also produce protective immunogenicity against the disease.[39] WHO/ICH requirement of O-acetylation positive for serogroups C, W-135, and Y is disadvantage for the vaccine manufacturers in the selection of high yielding polysaccharide producing O-acetylation groups.

Chemical structures of polysaccharides vaccines

See also

Notes

References

  1. ↑ Requirement from Saudi govt. for the umrah and hajj: http://new.wales.gov.uk/dphhp/publication/protection/immunisation/hajj/english.pdf?lang=en
  2. ↑ "UNITED NATIONS: Insufficient meningitis vaccine in Africa, WHO says". IRIN. UN Office for the Coordination of Humanitarian Affairs.
  3. ↑ Meningococcal Meningitis at eMedicine
  4. ↑ Trotter CL, Andrews NJ, Kaczmarski EB, Miller E, Ramsay ME (2004). "Effectiveness of meningococcal serogroup C conjugate vaccine 4 years after introduction". Lancet. 364 (9431): 365–7. doi:10.1016/S0140-6736(04)16725-1. PMID 15276396.
  5. 1 2 3 4 5 6 7 Bilukha OO, Rosenstein N (May 2005). "Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep. 54 (RR-7): 1–21. PMID 15917737.
  6. 1 2 3 4 American Academy of Pediatrics Committee on Infectious Diseases (August 2005). "Prevention and control of meningococcal disease: recommendations for use of meningococcal vaccines in pediatric patients". Pediatrics. 116 (2): 496–505. doi:10.1542/peds.2005-1314. PMID 15995007.
  7. ↑ Pichichero M, Casey J, Blatter M, et al. (January 2005). "Comparative trial of the safety and immunogenicity of quadrivalent (A, C, Y, W-135) meningococcal polysaccharide-diphtheria conjugate vaccine versus quadrivalent polysaccharide vaccine in two- to ten-year-old children". Pediatr. Infect. Dis. J. 24 (1): 57–62. doi:10.1097/01.inf.0000148928.10057.86. PMID 15665711.
  8. ↑ Centers for Disease Control and Prevention Advisory Committee on Immunization Practices, American Academy of Pediatrics, and American Academy of Family Physicians (January 2006). "Recommended childhood and adolescent immunization schedule—United States, 2006". Pediatrics. 117 (1): 239–40. doi:10.1542/peds.2005-2790. PMID 16396888.
  9. ↑ Centers for Disease Control and Prevention. Meningococcal disease among college students: ACIP modifies recommendations for meningitis vaccination. Press release. 1999 Oct 20 Routine primary immunization against meningococcal disease is recommended for most adults live in endemic areas and planning to travel such areas
  10. 1 2 3 Centers for Disease Control and Prevention (December 1997). "Immunization of health-care workers: recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Hospital Infection Control Practices Advisory Committee (HICPAC)". MMWR Recomm Rep. 46 (RR-18): 1–42. PMID 9427216.
  11. ↑ ACIP 2005 US military recruits should receive routine vaccinations while in service in endemic disease areas
  12. ↑ Centers for Disease Control and Prevention (2005). Health information for international travel, 2005–2006. Atlanta GA: US Department of Health and Human Services. Updates available from CDC website http://www.cdc.gov/travel/yb/index.htm).
    American College of Physicians. Task Force on Adult Immunization; Infectious Diseases Society of America (15 June 1994). Guide for adult immunization. American College of Physicians. pp. 30,34,46–47,51,54,65,103,146. ISBN 978-0-943126-23-4.
  13. ↑ Janoff EN, Tasker S, Opstad NL et al. Impact of immunization of recent HIV-1 seroconverters. Proceedings of ICAAC New Orleans 1996. Abstract No. I60
  14. ↑ Kroon FP, Bruisten S, Swieten PV et al. No increase in HIV-load following immunization with conjugate pneumococcal vaccine, Pneumovax, or Typhim-Vi. Proceedings of ICAAC New Orleans 1996. Abstract No. I61
  15. ↑ Tasker SA, Treanor J, Rossetti R et al. Whole virion influenza vaccine has protective efficacy in the setting of HIV infection. Proceedings of ICAAC New Orleans 1996. Abstract No. I88
  16. 1 2 3 4 Kirsch EA, Barton RP, Kitchen L, Giroir BP (November 1996). "Pathophysiology, treatment and outcome of meningococcemia: a review and recent experience". Pediatr. Infect. Dis. J. 15 (11): 967–78; quiz 979. doi:10.1097/00006454-199611000-00009. PMID 8933544.
  17. 1 2 Ross SC, Densen P (September 1984). "Complement deficiency states and infection: epidemiology, pathogenesis and consequences of neisserial and other infections in an immune deficiency". Medicine (Baltimore). 63 (5): 243–73. doi:10.1097/00005792-198409000-00001. PMID 6433145.
  18. ↑ Orren A, Potter PC, Cooper RC, du Toit E (October 1987). "Deficiency of the sixth component of complement and susceptibility to Neisseria meningitidis infections: studies in 10 families and five isolated cases". Immunology. 62 (2): 249–53. PMC 1453963Freely accessible. PMID 3679285.
  19. ↑ Ross SC, Rosenthal PJ, Berberich HM, Densen P (June 1987). "Killing of Neisseria meningitidis by human neutrophils: implications for normal and complement-deficient individuals". J. Infect. Dis. 155 (6): 1266–75. doi:10.1093/infdis/155.6.1266. PMID 3106511.
  20. ↑ Ross SC, Berberich HM, Densen P (December 1985). "Natural serum bactericidal activity against Neisseria meningitidis isolates from disseminated infections in normal and complement-deficient hosts". J. Infect. Dis. 152 (6): 1332–5. doi:10.1093/infdis/152.6.1332. PMID 3934293.
  21. ↑ Aldeen AA, Al' Cartwright KA (November 1996). "Neisseria meningitidis: vaccines and vaccine candidates". J. Infect. 33 (3): 153–7. doi:10.1016/S0163-4453(96)92081-2. PMID 8945702.
  22. ↑ Mayon-White RT, Heath PT (March 1997). "Preventative strategies on meningococcal disease". Arch. Dis. Child. 76 (3): 178–81. doi:10.1136/adc.76.3.178. PMC 1717118Freely accessible. PMID 9135255.
  23. ↑ Andreoni J, Käyhty H, Densen P (July 1993). "Vaccination and the role of capsular polysaccharide antibody in prevention of recurrent meningococcal disease in late complement component-deficient individuals". J. Infect. Dis. 168 (1): 227–31. doi:10.1093/infdis/168.1.227. PMID 8515116.
  24. 1 2 3 Cunliffe NA, Snowden N, Dunbar EM, Haeney MR (July 1995). "Recurrent meningococcal septicaemia and properdin deficiency". J. Infect. 31 (1): 67–8. doi:10.1016/S0163-4453(95)91550-8. PMID 8522838.
  25. ↑ "Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep. 49 (RR-7): 1–10. June 2000. PMID 10902834.
    Centers for Disease Control and Prevention (June 2000). "Meningococcal disease and college students. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR Recomm Rep. 49 (RR-7): 13–20. PMID 10902835.
  26. ↑ "Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence". MMWR Recomm Rep. 42 (RR-4): 1–18. April 1993. PMID 8474421.
  27. ↑ Jennings HJ (1990). "Capsular polysaccharides as vaccine candidates". Curr. Top. Microbiol. Immunol. 150: 97–127. PMID 2105188.
  28. ↑ Artenstein MS, Gold R, Zimmerly JG, Wyle FA, Schneider H, Harkins C (February 1970). "Prevention of meningococcal disease by group C polysaccharide vaccine". N. Engl. J. Med. 282 (8): 417–20. doi:10.1056/NEJM197002192820803. PMID 4983754.
  29. ↑ Peltola H, Mäkelä H, Käyhty H, et al. (September 1977). "Clinical efficacy of meningococcus group A capsular polysaccharide vaccine in children three months to five years of age". N. Engl. J. Med. 297 (13): 686–91. doi:10.1056/NEJM197709292971302. PMID 408682.
  30. 1 2 Reingold AL, Broome CV, Hightower AW, et al. (July 1985). "Age-specific differences in duration of clinical protection after vaccination with meningococcal polysaccharide A vaccine". Lancet. 2 (8447): 114–8. doi:10.1016/S0140-6736(85)90224-7. PMID 2862316.
  31. ↑ Brandt BL, Artenstein MS (May 1975). "Duration of antibody responses after vaccination with group C Neisseria meningitidis polysaccharide". J. Infect. Dis. 131 (Suppl): S69–72. doi:10.1093/infdis/131.supplement.s69. PMID 805191.
  32. ↑ Käyhty H, Karanko V, Peltola H, Sarna S, Mäkelä PH (December 1980). "Serum antibodies to capsular polysaccharide vaccine of group A Neissera meningitidis followed for three years in infants and children". J. Infect. Dis. 142 (6): 861–8. doi:10.1093/infdis/142.6.861. PMID 6780634.
  33. ↑ Ceesay SJ, Allen SJ, Menon A, et al. (May 1993). "Decline in meningococcal antibody levels in African children 5 years after vaccination and the lack of an effect of booster immunization". J. Infect. Dis. 167 (5): 1212–6. doi:10.1093/infdis/167.5.1212. PMID 8486957.
  34. ↑ Nahm, M. H., M. A. Apicella, and D. E. Briles. 1999. Immunity to extracellular bacteria, p. 1373–1386. In W. E. Paul (ed.), Fundamental immunology, 4th ed. Lippincott-Raven Publishers, Philadelphia, Pa.
  35. 1 2 Mond JJ, Lees A, Snapper CM (1995). "T cell-independent antigens type 2". Annu. Rev. Immunol. 13: 655–92. doi:10.1146/annurev.iy.13.040195.003255. PMID 7612238.
  36. ↑ Robbins JB, Schneerson R, Anderson P, Smith DH (October 1996). "The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines". JAMA. 276 (14): 1181–5. doi:10.1001/jama.276.14.1181. PMID 8827975.
  37. ↑ Lemercinier X, Jones C (December 1996). "Full 1H NMR assignment and detailed O-acetylation patterns of capsular polysaccharides from Neisseria meningitidis used in vaccine production". Carbohydr. Res. 296: 83–96. doi:10.1016/S0008-6215(96)00253-4. PMID 9008844.
  38. ↑ Yang Q, Jennings H (2001). "Purification of capsular polysaccharide". Methods Mol. Med. 66: 41–7. doi:10.1385/1-59259-148-5:41. PMID 21336745.
  39. ↑ Harrison LH (January 2006). "Prospects for Vaccine Prevention of Meningococcal Infection" (PDF). Clin. Microbiol. Rev. 19 (1): 142–64. doi:10.1128/CMR.19.1.142-164.2006. PMC 1360272Freely accessible. PMID 16418528.
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