NmVac4-A/C/Y/W-135

NmVac4-A/C/Y/W-135 is the commercial name of the polysaccharide vaccine against the bacterium (specifically serogroups A, C, Y, and W-135) that causes meningococcal meningitis. The product, by JN-International Medical Corporation, is designed and formulated to be used in developing countries for protecting populations during meningitis disease epidemics.

NmVac4-A/C/Y/W-135

Vaccine description
Target	Neisseria meningitidis A,C,Y,W-135
Vaccine type	Polysaccharide
Clinical data
Routes of administration	Intramuscular(IM)
ATC code	J07AH04 (WHO)
Identifiers
ChemSpider	none
^NY (what is this?)  (verify)

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. After fermentation, the polysaccharides are purified, formulated, and lyophilized using preservatives and stabilizers to make a vaccine product. The vaccine cannot protect from other serogroups of N. meningitidis and cannot eliminate the chance of infection by these serogroups.

Medical uses

Initial vaccination of children

Children two to ten years of age who are at high risk for meningococcal disease, especially those with certain chronic medical conditions and those who travel to or reside in countries with hyper-endemic or epidemic meningococcal disease. Although safety and efficacy of the vaccine have not been established in children younger than two years of age and under outbreak control, the unconjugated vaccine can be considered. Safety and efficacy of NmVac4 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.^[1][2][3][4]

Adolescents 11 years of age or older

It is recommend that primary immunization against meningococcal disease with NmVac4 for all young adolescents at 11–12 years of age and all unvaccinated older adolescents at 15 years of age. Although NmVac4 is the preferred meningococcal vaccine in adolescents 11 years of age or older, NmVac4 is an acceptable alternative if the conjugated vaccine is unavailable.^[2][3][5]

Adults

College students who plan to live in dormitories receive primary immunization with NmVac4. 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.^[6] Although NmVac4 is the preferred meningococcal vaccine in adults 55 years of age or younger, NmVac4 is an acceptable alternative for adults in this age group if the conjugated vaccine is unavailable. Since safety and efficacy of NmVac4 in adults older than 55 years of age have not been established to date, NmVac4 should be used for primary immunization in this group.^[2][3]

Medical staff and laboratory personnel

Health care workers and laboratory personnel who are routinely exposed to isolates of N. meningitidis are recommended to receive routine immunization against meningococcal disease. Laboratory personnel and medical staff are at increased risk of exposure to N. meningitidis or to people with meningococcal disease. Hospital Infection Control Practices Advisory Committee (HICPAC) recommendations regarding immunization of health-care workers state 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 NmVac4 as can 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 intramuscular ceftriaxone or a single dose of oral ciprofloxacin).^[2][7]

Military recruits

Because the risk of meningococcal disease is increased among military recruits, all military recruits routinely receive primary immunization against the disease.^[8]

Travelers

Only Saudi Arabia requires 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.^[2][3] 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 ^[2][9] The vaccine (containing serogroups A, C, Y, and W-135) is currently required by Saudi Arabia for pilgrims visiting Mecca for the Hajj or for the Umrah.^[10]

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.^[7] Although efficacy of NmVac4 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.^[7] Vaccination against meningococcus does 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.^[11][12][13]

Close contacts of 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, 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.^[2]

Other

Inherited properdin deficiency also is related with an increased risk of contracting meningococcal disease.^[14][15] People with a functional or anatomic lack of spleen function may not efficiently clear encapsulated Neisseria meningitidis from the bloodstream and are at increased risk of infection.^[14][15] Persons with other conditions associated with immunosuppression also may be at increased risk of developing meningitis disease.^[16][17]

People with component deficiencies in the final common complement pathway (C3, C5–C9) are more susceptible to N. meningitidis infection than complement-satisfactory people,^{[14][18][19][20][21][22][23]} and it was estimated that the risk of infection is 7,000 times higher in such individuals.^[18] In addition, complement component-deficient population frequently experience frequent meningococcal disease,^[24] since their immune response to natural infection may be less complete than that of complement none-deficient people.^[14][15]

Contraindications

The safety of the vaccine in pregnant women has not been established. The safety of this vaccine in the people with chronic medical conditions has not been established.

Pharmacodynamics

Formulation

The vaccine contains 50 mcg of purified polysaccharide for each of the serogroups (A, C, Y, and W135) in a lyophilized form. The active pharmaceutical ingredient of the 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:^[25][26]

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.^[27] 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

•  
  Fig.1 N. meningitidis group A
•  
  Fig.2 N. meningitidis group C
•  
  Fig.3 N. meningitidis group Y
•  
  Fig.4 N. meningitidis group W-135

References

1. 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): 365–367. doi:10.1016/S0140-6736(04)16725-1. PMID 15276396. S2CID 8759414.
2. Bilukha OO, Rosenstein N (May 2005). "Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. Recommendations and Reports. 54 (RR-7): 1–21. PMID 15917737.
3. 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. S2CID 20859458.
4. Pichichero M, Casey J, Blatter M, Rothstein E, Ryall R, Bybel 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". The Pediatric Infectious Disease Journal. 24 (1): 57–62. doi:10.1097/01.inf.0000148928.10057.86. PMID 15665711. S2CID 23012002.
5. Centers for Disease Control and Prevention Advisory Committee on Immunization Practices, American Academy of Pediatrics, American Academy of Family Physicians (January 2006). "Recommended childhood and adolescent immunization schedule--United States, 2006". Pediatrics. 117 (1): 239–240. doi:10.1542/peds.2005-2790. PMID 16396888.
6. 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
7. 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. Recommendations and Reports. 46 (RR-18): 1–42. PMID 9427216.
8. Bilukha OO, Rosenstein N, et al. (National Center for Infectious Diseases, Centers for Disease Control and Prevention (CDC)) (May 2005). "Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. Recommendations and Reports: Morbidity and Mortality Weekly Report. Recommendations and Reports. 54 (RR-7): 1–21. PMID 15917737. Military recruits should receive routine vaccinations while in service in endemic disease areas
9. "Health information for international travel, 2005–2006". Centers for Disease Control and Prevention. Atlanta GA: US Department of Health and Human Services. 2005.
   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.
10. "Requirement from Saudi govt. for the Umrah and Hajj".
11. Janoff EN, Tasker S, Opstad NL, et al. (1996). Impact of immunization of recent HIV-1 seroconverters. Proceedings of ICAAC New Orleans. Abstract No. I60.
12. Kroon FP, Bruisten S, Swieten PV, et al. (1996). No increase in HIV-load following immunization with conjugate pneumococcal vaccine, Pneumovax, or Typhim-Vi. Proceedings of ICAAC New Orleans. Abstract No. I61.
13. Tasker SA, Treanor J, Rossetti R, et al. (1996). Whole virion influenza vaccine has protective efficacy in the setting of HIV infection. Proceedings of ICAAC New Orleans. Abstract No. I88.
14. Kirsch EA, Barton RP, Kitchen L, Giroir BP (November 1996). "Pathophysiology, treatment and outcome of meningococcemia: a review and recent experience". The Pediatric Infectious Disease Journal. 15 (11): 967–78, quiz 979. doi:10.1097/00006454-199611000-00009. PMID 8933544.
15. Cunliffe NA, Snowden N, Dunbar EM, Haeney MR (July 1995). "Recurrent meningococcal septicaemia and properdin deficiency". The Journal of Infection. 31 (1): 67–68. doi:10.1016/S0163-4453(95)91550-8. PMID 8522838.
16. "Prevention and control of meningococcal disease. Recommendations of the Advisory Committee on Immunization Practices (ACIP)". MMWR. Recommendations and Reports. 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. Recommendations and Reports. 49 (RR-7): 13–20. PMID 10902835.
17. "Recommendations of the Advisory Committee on Immunization Practices (ACIP): use of vaccines and immune globulins for persons with altered immunocompetence". MMWR. Recommendations and Reports. 42 (RR-4): 1–18. April 1993. PMID 8474421.
18. 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. 63 (5): 243–273. doi:10.1097/00005792-198409000-00001. PMID 6433145. S2CID 25041064.
19. 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): 249–253. PMC 1453963. PMID 3679285.
20. Ross SC, Rosenthal PJ, Berberich HM, Densen P (June 1987). "Killing of Neisseria meningitidis by human neutrophils: implications for normal and complement-deficient individuals". The Journal of Infectious Diseases. 155 (6): 1266–1275. doi:10.1093/infdis/155.6.1266. PMID 3106511.
21. 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". The Journal of Infectious Diseases. 152 (6): 1332–1335. doi:10.1093/infdis/152.6.1332. PMID 3934293.
22. Al'Aldeen AA, Cartwright KA (November 1996). "Neisseria meningitidis: vaccines and vaccine candidates". The Journal of Infection. 33 (3): 153–157. doi:10.1016/S0163-4453(96)92081-2. PMID 8945702.
23. Mayon-White RT, Heath PT (March 1997). "Preventative strategies on meningococcal disease". Archives of Disease in Childhood. 76 (3): 178–181. doi:10.1136/adc.76.3.178. PMC 1717118. PMID 9135255.
24. 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". The Journal of Infectious Diseases. 168 (1): 227–231. doi:10.1093/infdis/168.1.227. PMID 8515116.
25. 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". Carbohydrate Research. 296 (1–4): 83–96. doi:10.1016/S0008-6215(96)00253-4. PMID 9008844.
26. Yang Q, Jennings H (2001). "Purification of capsular polysaccharide". Meningococcal Vaccines. Methods in Molecular Medicine. Vol. 66. pp. 41–47. doi:10.1385/1-59259-148-5:41. ISBN 1-59259-148-5. PMID 21336745.
27. Harrison LH (January 2006). "Prospects for vaccine prevention of meningococcal infection". Clinical Microbiology Reviews. 19 (1): 142–164. doi:10.1128/CMR.19.1.142-164.2006. PMC 1360272. PMID 16418528.

Notes

• Product Brochure
• Vaccine Clinical Trials multimedia presentation of clinical trial within the Meningitis Belt of sub-Saharan Africa.
• http://www.jn-vaccines.org/NmVac4.pdf