NmVac4-A/C/Y/W-135

NmVac4-A/C/Y/W-135

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, 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.

Indications

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→

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

  • Product Brochure
  • Vaccine Clinical Trials multimedia presentation of clinical trial within the Meningitis Belt of sub-Saharan Africa.

References

External links

  • http://www.jn-vaccines.org/NmVac4.pdf