NmVac4-A/C/Y/W-135

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NmVac4-A/C/Y/W-135
Meningococcal meningitis A,C,Y,W-135 Vaccine.png
Vaccine description
Target Neisseria meningitidis serotypes A, C, Y, W-135
Vaccine type Polysaccharide
Clinical data
Routes of
administration 		Intramuscular (IM)
ATC code
Identifiers
ChemSpider
  • none
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NmVac4-A/C/Y/W-135 is the commercial name for a polysaccharide vaccine that protects against meningococcal meningitis caused by Neisseria meningitidis , specifically the serotypes A, C, Y, and W-135. This vaccine is part of a broader group of meningococcal vaccines. It is especially formulated for use in developing countries, aimed at protecting populations during meningitis outbreaks, particularly in high-risk regions like the African meningitis belt.

Contents

Meningococcal meningitis is a bacterial infection caused by the Neisseria meningitidis bacterium, commonly known as meningococcus. The vaccine is created using bacterial capsular polysaccharides derived from each of the targeted serogroups through fermentation processes in bioreactors. Following fermentation, the polysaccharides are purified, stabilized, and lyophilized with preservatives to create the final vaccine product.

While effective against serogroups A, C, Y, and W-135, the vaccine does not provide protection against other meningococcal serogroups and does not eliminate the risk of infection by these other groups.

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]

GroupStructure 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

Related Research Articles

<i>Neisseria</i> Genus of bacteria

Neisseria is a large genus of bacteria that colonize the mucosal surfaces of many animals. Of the 11 species that colonize humans, only two are pathogens, N. meningitidis and N. gonorrhoeae.

<span class="mw-page-title-main">Varicella zoster virus</span> Herpes virus that causes chickenpox and shingles

Varicella zoster virus (VZV), also known as human herpesvirus 3 or Human alphaherpesvirus 3 (taxonomically), is one of nine known herpes viruses that can infect humans. It causes chickenpox (varicella) commonly affecting children and young adults, and shingles in adults but rarely in children. As a late complication of VZV infection, Ramsay Hunt syndrome type 2 may develop in rare cases. VZV infections are species-specific to humans. The virus can survive in external environments for a few hours.

<span class="mw-page-title-main">Conjugate vaccine</span> Type of vaccine

A conjugate vaccine is a type of subunit vaccine which combines a weak antigen with a strong antigen as a carrier so that the immune system has a stronger response to the weak antigen.

<span class="mw-page-title-main">Pneumococcal polysaccharide vaccine</span> Pneumonia vaccine

Pneumococcal polysaccharide vaccine, sold under the brand name Pneumovax 23, is a pneumococcal vaccine that is used for the prevention of pneumococcal disease caused by the 23 serotypes of Streptococcus pneumoniae contained in the vaccine as capsular polysaccharides. It is given by intramuscular or subcutaneous injection.

<i>Neisseria meningitidis</i> Species of bacterium that can cause meningitis

Neisseria meningitidis, often referred to as the meningococcus, is a Gram-negative bacterium that can cause meningitis and other forms of meningococcal disease such as meningococcemia, a life-threatening sepsis. The bacterium is referred to as a coccus because it is round, and more specifically a diplococcus because of its tendency to form pairs.

<span class="mw-page-title-main">Meningococcal disease</span> Often life-threatening bacterial infection

Meningococcal disease describes infections caused by the bacterium Neisseria meningitidis. It has a high mortality rate if untreated but is vaccine-preventable. While best known as a cause of meningitis, it can also result in sepsis, which is an even more damaging and dangerous condition. Meningitis and meningococcemia are major causes of illness, death, and disability in both developed and under-developed countries.

The Advisory Committee on Immunization Practices (ACIP) is a committee within the United States Centers for Disease Control and Prevention (CDC) that provides advice and guidance on effective control of vaccine-preventable diseases in the U.S. civilian population. The ACIP develops written recommendations for routine administration of vaccines to the pediatric and adult populations, along with vaccination schedules regarding appropriate timing, dosage, and contraindications of vaccines. ACIP statements are official federal recommendations for the use of vaccines and immune globulins in the U.S., and are published by the CDC.

<span class="mw-page-title-main">Pneumococcal conjugate vaccine</span> Vaccine against Strep pneumoniae

Pneumococcal conjugate vaccine is a pneumococcal vaccine made with the conjugate vaccine method and used to protect infants, young children, and adults against disease caused by the bacterium Streptococcus pneumoniae (pneumococcus). It contains purified capsular polysaccharide of pneumococcal serotypes conjugated to a carrier protein to improve antibody response compared to the pneumococcal polysaccharide vaccine. The World Health Organization (WHO) recommends the use of the conjugate vaccine in routine immunizations given to children.

<span class="mw-page-title-main">Hepatitis B vaccine</span> Vaccine against hepatitis B

Hepatitis B vaccine is a vaccine that prevents hepatitis B. The first dose is recommended within 24 hours of birth with either two or three more doses given after that. This includes those with poor immune function such as from HIV/AIDS and those born premature. It is also recommended that health-care workers be vaccinated. In healthy people, routine immunization results in more than 95% of people being protected.

<span class="mw-page-title-main">Hib vaccine</span> Haemophilus influenzae type B vaccine

The Haemophilus influenzae type B vaccine, also known as Hib vaccine, is a vaccine used to prevent Haemophilus influenzae type b (Hib) infection. In countries that include it as a routine vaccine, rates of severe Hib infections have decreased more than 90%. It has therefore resulted in a decrease in the rate of meningitis, pneumonia, and epiglottitis.

Pneumococcal infection is an infection caused by the bacterium Streptococcus pneumoniae.

<span class="mw-page-title-main">Jeeri R. Reddy</span>

Jeeri Reddy an American biologist who became an entrepreneur, developing new generation preventive and therapeutic vaccines. He has been an active leader in the field of the biopharmaceutical industry, commercializing diagnostics and vaccines through JN-International Medical Corporation. He is the scientific director and president of the corporation that created the world's first serological rapid tests for Tuberculosis to facilitate acid-fast bacilli microscopy for the identification of smear-positive and negative cases. Prevention of mother-to-child transmission of HIV was achieved in South East Asia by the use of rapid tests developed by Reddy in 1999. Reddy through his Corporation donated $173,050 worth of Rapid Diagnostic Tests (RDTs) for malaria in Zambia and actively participated in the prevention of child deaths due to Malaria infections. Reddy was personally invited by the president, George W. Bush, and First Lady Laura Bush to the White House for Malaria Awareness Day sponsored by US President Malaria Initiative (PMI) on Wednesday, April 25, 2007.

<span class="mw-page-title-main">Meningitis</span> Inflammation of the membranes around the brain and spinal cord

Meningitis is acute or chronic inflammation of the protective membranes covering the brain and spinal cord, collectively called the meninges. The most common symptoms are fever, intense headache, vomiting and neck stiffness and occasionally photophobia.

Meningococcal vaccine refers to any vaccine used to prevent infection by Neisseria meningitidis. Different versions are effective against some or all of the following types of meningococcus: A, B, C, W-135, and Y. The vaccines are between 85 and 100% effective for at least two years. They result in a decrease in meningitis and sepsis among populations where they are widely used. They are given either by injection into a muscle or just under the skin.

<span class="mw-page-title-main">African meningitis belt</span> Region of Africa with high rate of incidence of meningitis

The African meningitis belt is a region in sub-Saharan Africa where the rate of incidence of meningitis is very high. It extends from Senegal to Ethiopia, and the primary cause of meningitis in the belt is Neisseria meningitidis.

MenAfriVac is a vaccine developed for use in sub-Saharan Africa for children and adults between 9 months and 29 years of age against meningococcal bacterium Neisseria meningitidis group A. The vaccine costs less than US$0.50 per dose.

Sir Andrew John Pollard is the Ashall Professor of Infection & Immunity at the University of Oxford and a Fellow of St Cross College, Oxford. He is an Honorary Consultant Paediatrician at John Radcliffe Hospital and the Director of the Oxford Vaccine Group. He is the Chief Investigator on the University of Oxford COVID-19 Vaccine trials and has led research on vaccines for many life-threatening infectious diseases including typhoid fever, Neisseria meningitidis, Haemophilus influenzae type b, streptococcus pneumoniae, pertussis, influenza, rabies, and Ebola.

Trudy Virginia Noller Murphy is an American pediatric infectious diseases physician, public health epidemiologist and vaccinologist. During the 1980s and 1990s, she conducted research at Southwestern Medical School in Dallas, Texas on three bacterial pathogens: Haemophilus influenzae type b (Hib), Streptococcus pneumoniae (pneumococcus), and methicillin-resistant Staphylococcus aureus (MRSA). Murphy's studies advanced understanding of how these organisms spread within communities, particularly among children attending day care centers. Her seminal work on Hib vaccines elucidated the effects of introduction of new Hib vaccines on both bacterial carriage and control of invasive Hib disease. Murphy subsequently joined the National Immunization Program at the Centers for Disease Control and Prevention (CDC) where she led multi-disciplinary teams in the Divisions of Epidemiology and Surveillance and The Viral Hepatitis Division. Among her most influential work at CDC was on Rotashield™, which was a newly licensed vaccine designed to prevent severe diarrheal disease caused by rotavirus. Murphy and her colleagues uncovered that the vaccine increased the risk of acute bowel obstruction (intussusception). This finding prompted suspension of the national recommendation to vaccinate children with Rotashield, and led the manufacturer to withdraw the vaccine from the market. For this work Murphy received the United States Department of Health and Human Services Secretary's Award for Distinguished Service in 2000, and the publication describing this work was recognized in 2002 by the Charles C. Shepard Science Award from the Centers for Disease Control and Prevention.

Dan M. Granoff is an infectious disease physician-scientist who was named the 2014 Maurice Hilleman/Merck Laureate by the American Society for Microbiology for outstanding contributions to vaccine discovery and development. Beginning in 2011, Granoff held the Clorox Foundation Endowed Chair and was director of the Center of Immunobiology and Vaccine Development at Children's Hospital Oakland Research Institute. His work increased understanding of basic mechanisms of human immunity to encapsulated bacteria, and furthered development of vaccines against Haemophilus influenzae type B (Hib) and Neisseria meningitidis.

Penbraya is a pentavalent conjugate vaccine developed by Pfizer for the prevention of invasive meningococcal disease in people 10 through 25 years of age. Invasive meningococcal disease, caused by the bacterium Neisseria meningitidis, can lead to serious conditions such as meningitis and sepsis. Penbraya is approved for use by the US Food and Drug Administration (FDA). Penbraya is the first pentavalent vaccine that provides coverage against the five most common serogroups causing meningococcal disease.

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. 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. Recommendations and Reports. 54 (RR-7): 1–21. PMID   15917737.
  3. 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. 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. 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. 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. 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". The Pediatric Infectious Disease Journal. 15 (11): 967–78, quiz 979. doi:10.1097/00006454-199611000-00009. PMID   8933544.
  15. 1 2 3 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. 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. 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.

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