Neisseria meningitidis, also simply known as meningococcus, is a Gram-negative β-proteobacterium and member of the bacterial family Neisseriaceaeis. There are 13 serogroups based on different capsular polysaccharide structures. Among them, six serogroups (A, B, C, W-135, X, and Y) cause most life-threatening disease (Stephens et al., 2007).
4. Microbial Pathogenesis
Meningococcus is spread through the exchange of saliva and other respiratory secretions during activities like coughing, kissing, and chewing on toys. Those with impaired immunity may be easier to get meningococcus. Meningococcal virulence is related to both capsule expression, expression of other surface structures, and underlying genotype. N meningitidis pathogenesis is related to its ability to express and modify capsule with serogroups A, B, C, W-135, X, and Y. Capsules of N meningitidis facilitate transmission and colonisation, and protect the meningococcus from desiccation, phagocytic killing, opsonisation, and complement-mediated bactericidal killing. Outer membrane proteins (e.g., PorB, PorA , Opa and Opc) contribute to meningococcal virulence. Outer membrane porins are involved in host-cell interactions and as targets for bactericidal antibodies. Endotoxin, or lipo-oligosaccharide, a major component of the outer membrane, differs in structure from enteric endotoxins and is crucial in inflammatory signalling via Toll-like receptor 4 (TLR4) (Stephens et al., 2007).
5. Host Ranges and Animal Models
It only infects humans; there is no animal reservoir.
6. Host Protective Immunity
N. mengingitidis establishes systemic infections only in individuals who lack serum bacterial antibodies directed against the capsular or noncapsular (cell wall) antigens of the invading strain, or in patients deficient in the late-acting complement components. The presence of serum bactericidal IgG and IgM is probably the most important host factor in preventing invasive disease. The role of bactericidal antibodies in prevention of invasive disease explains why high attack rates are seen in infants from 6 to 9 months old, the time at which maternal antibodies are being lost. Individuals with complement deficiencies (C5, C6, C7, or C8) may develop meningococcemia despite protective antibody. This emphasizes the importance of the complement system in defense against meningococcal disease (Textbook of Bacteriology).
>NP_274732.1 biopolymer transport protein [Neisseria meningitidis MC58]
MNLKLVFESGDPVLIGVFVLMLLMSIVTWCLVVLRCIKLYRARKGNAAVKRHMRDTLSLNDAVEKVRAVD
APLSKLAQEALQSYRNYRRNEASELAQALPLNEYLVIQIRNSMAQIMRRFDYGMTALASIGATAPFIGLF
GTVWGIYHALINIGQSGQMSIAAVAGPIGEALVATAAGLFVAIPAVLAYNFLNRGTKILTQDLDAMAHDL
HVRLLNQKDS
Molecule Role :
Protective antigen
Molecule Role Annotation :
A total of 11 meningococcal proteins that are necessary for establishing systemic infection were expressed as recombinant antigens and assessed for their ability to protect mice against live bacterial challenge against N. meningitidis; ExbB, which is required for iron acquisition, elicited protective immunity (Sun et al., 2005).
Molecule Role Annotation :
he DNA construct induced a significant anti-polysaccharide antibody response that was bactericidal. Mice immunized with the DNA construct were subsequently protected against challenge with a lethal dose of N. meningitidis serogroup C.(Prinz et al., 2003)
Molecule Role Annotation :
A total of 11 meningococcal proteins that are necessary for establishing systemic infection were expressed as recombinant antigens and assessed for their ability to protect mice against live bacterial challenge against N. meningitidis; the lactate permease (LctP) elicited protective immunity (Sun et al., 2005).
>CAA57206.1 outer membrane protein P64k or PM-6, partial [Neisseria meningitidis]
MALVELKVPDIGGHENVDIIAVEVNVGDTIAVDDTLITLETDKATMDIPAEVAGVVKEVKVKVGDKISEG
GLIVVVEAEGAATAPKAEAPATPAQEAPKAAAPAPQAAQFGGSADAEYDVVLGGGPGGYSAAFAAADEGL
KVAIVERYKTLGGVCLNVGCIPSKALLHNAAVIDEVRHLAANGIKYPEPELDIDMLRAYKNGVVSRLTGG
LAGMAKRRKVDVIQGDGQFLDPHHLEVSLTAGDAYEQAAPTGEKKIVAFKNCIIAAGSRVTKLPFIPEDP
RIIDSSGALALKEVPGKLLIIGAGIIGLEMGTVYSTLGSRLDVVEMMDGLMQGADRDLVKVWQKQNEYRF
DNIMVNTKTVAVEPKEDGVYVTFEGANAPKEPQRYDAVLVAAGRAPNGKLISAEKAGVAVTDRGFIEVDK
QMRTNVPHIYAIVDIVGQPMLAHKAVHEGHVAAENCAGHKAYFDARVIPGVAYTSPEVAWVGETELSAKA
SGRKITKANFPWAASGRAIANGCDNGFTKLIFDAETGRIIGGGIVGPNGGDMIGEVCLAIEMGCDAADIG
KTIHPHPTLGESIGMAAEVALGTCTDLPPQKKK
Molecule Role :
Other
Molecule Role Annotation :
Sera of the challenge group immunized with CCPS-P64kR showed a three-fold higher bactericidal response than the sera of the group immunized with the plain CCPS and they were able to protect against challenge with Neisseria meningococci in the infant rat protection model (Carmenate et al., 2004).
Molecule Role Annotation :
A metH mutant, in combination with a siaD mutation, is attenuated in mice and induces significant protection from challenge with wild type N. meningitidis (Li et al., 2004).
Molecule Role Annotation :
Protective antigen (Giuliani et al., 2006; Comanducci et al., 2002). There is another nadA (quinolinate synthetase) [ Neisseria meningitidis MC58 ] with GeneID: 902509. However, according to sequence analysis, this nadA is not the same NadA that was found to be protective antigen (Giuliani et al., 2006; Comanducci et al., 2002).
>NP_273705.1 outer membrane protein [Neisseria meningitidis MC58]
MKKALATLIALALPAAALAEGASGFYVQADAAHAKASSSLGSAKGFSPRISAGYRINDLRFAVDYTRYKN
YKAPSTDFKLYSIGASAIYDFDTQSPVKPYLGARLSLNRASVDLGGSDSFSQTSIGLGVLTGVSYAVTPN
VDLDAGYRYNYIGKVNTVKNVRSGELSAGVRVKF
Molecule Role :
Protective antigen
Molecule Role Annotation :
Protective antigen (Martin et al., 1997) NspA-containing outer membrane vesicles conferred protection against otherwise lethal intraperitoneal challenge of mice with N. meningitidis serogroup B, and sera raised against them mediated opsonophagocytosis of meningococcal strains expressing this antigen (O'dwyer et al., 2004).
Molecule Role Annotation :
Seventeen monoclonal antibodies to one of three main cell surface antigens of Neisseria meningitidis group B were tested for protective efficacy in the infant rat using as challenge seven strains of different class 2/3 protein serotypes. Survival of the animals was regularly obtained with antibodies to the P1 protein and to LPS (Saukkonen et al., 1989).
Molecule Role Annotation :
An rfaF mutant, in combination with a siaD mutation, is attenuated in mice and induces significant protection from challenge with wild type N. meningitidis (Li et al., 2004).
>gi|15677983|ref|NP_273131.1| polysialic acid capsule biosynthesis protein SiaD [Neisseria meningitidis MC58]
MLKKIKKALFQPKKFFQDSMWLTTSPFYLTPPRNNLFVISNLGQLNQVQSLIKIQKLTNNLLVILYTSKN
LKMPKLVHQSANKNLFESIYLFELPRSPNNITPKKLLYIYRSYKKILNIIQPAHLYMLSFTGHYSYLISI
AKKKNITTHLIDEGTGTYAPLLESFSYHPTKLERYLIGNNLNIKGYIDHFDILHVPFPEYAKKIFNAKKY
NRFFAWRKGDVLQGD
Molecule Role :
Virmugen
Molecule Role Annotation :
A siaD mutant, in combination with either a metH or rfaF mutation, is attenuated in mice and induces protection from challenge with wild type N. meningitidis (Li et al., 2004).
>NP_273507.1 transferrin-binding protein B [Neisseria meningitidis MC58]
MNNPLVNQAAMVLPVFLLSACLGGGGSFDLDSVDTEAPRPAPKYQDVFSEKPQAQKDQGGYGFAMRLKRR
NWYPQAKEDEVKLDESDWEATGLPDEPKELPKRQKSVIEKVETDSDNNIYSSPYLKPSNHQNGNTGNGIN
QPKNQAKDYENFKYVYSGWFYKHAKREFNLKVEPKSAKNGDDGYIFYHGKEPSRQLPASGKITYKGVWHF
ATDTKKGQKFREIIQPSKSQGDRYSGFSGDDGEEYSNKNKSTLTDGQEGYGFTSNLEVDFHNKKLTGKLI
RNNANTDNNQATTTQYYSLEAQVTGNRFNGKATATDKPQQNSETKEHPFVSDSSSLSGGFFGPQGEELGF
RFLSDDQKVAVVGSAKTKDKPANGNTAAASGGTDAAASNGAAGTSSENGKLTTVLDAVELKLGDKEVQKL
DNFSNAAQLVVDGIMIPLLPEASESGNNQANQGTNGGTAFTRKFDHTPESDKKDAQAGTQTNGAQTASNT
AGDTNGKTKTYEVEVCCSNLNYLKYGMLTRKNSKSAMQAGESSSQADAKTEQVEQSMFLQGERTDEKEIP
SEQNIVYRGSWYGYIANDKSTSWSGNASNATSGNRAEFTVNFADKKITGTLTADNRQEATFTIDGNIKDN
GFEGTAKTAESGFDLDQSNTTRTPKAYITDAKVQGGFYGPKAEELGGWFAYPGDKQTKNATNASGNSSAT
VVFGAKRQQPVR
Molecule Role :
Protective antigen
Molecule Role Annotation :
Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth (Lissolo et al., 1995).
>AAF81744.1 transferrin-binding protein A [Neisseria meningitidis]
MQQQHLFRFNILCLSLMTALPAYAENVQAGQAQEKQLDTIQVKAKKQKTRRDNEVTGLGKLVKSSDTLSK
EQVLNIRDLTRYDPGIAVVEQGRGASSGYSIRGMDKNRVSLTVDGVSQIQSYTAQAALGGTRTAGSSGAI
NEIEYENVKAVEISKGSNSVEQGSGALAGSVAFQTKTADDVIGEGRQWGIQSKTAYSGKNRGLTQSIALA
GRIGGAEALLIHTGRRAGEIRAHEDAGRGVQSFNRLVPVEDSSNYAYFIVKEECKNGSYETCKANPKKDV
VGKDERQTVSTRDYTGPNRFLADPLSYESRSWLFRPGFRFENKRHYIGGILEHTQQTFDTRDMTVPAFLT
KAVFDANKKQAGSLPGNGKYAGNHKYGGLFTNGENGALVGAEYGTGVFYDETHTKSRYGLEYVYTNADKD
TWADYARLSYDRQGVGLDNHFQQTHCSADGSDKYCRPSADKPFSYYKSDRVIYGESHRLLQAAFKKSFDT
AKIRHNLSVNLGFDRFGSNLRHQDYYYQHANRAYSSNTPPQNNGKKISPNGSETSPYWVTIGRGNVVTGQ
ICRLGNNTYTDCTPRSINGKSYYAAVRDNVRLGRWADVGAGLRYDYRSTHSDDGSVSTGTHRTLSWNAGI
VLKPTDWLDLTYRTSTGFRLPSFAEMYGWRAGVQSKAVKIDPEKSFNKEAGIVFKGDFGNLEASWFNNAY
RDLIVRGYEAQIKDGKEEAKGDPAYLNAQSARITGINILGKIDWNGVWDKLPEGWYSTFAYNRVRVRDIK
KRADRTDIQSHLFDAIQPSRYVVGLGYDQPEGKWGVNGMLTYSKAKEITELLGSRALLNGNSRNTKATAR
RTRPWYIVDVSGYYTVKKHFTLRAGVYNLLNYRYVTWENVRQTAGGAVNQHKNVGVYNRYAAPGRNYTFS
LEMKF
Molecule Role :
Protective antigen
Molecule Role Annotation :
Recombinant TbpA protein was used in a mouse intraperitoneal-infection model to determine their ability to protect against meningococcal infection and to induce cross-reactive and bactericidal antibodies. TbpA was found to afford protection against meningococcal challenge when administered as the sole immunogen (West et al., 2001).
Description:
aluminum hydroxide combined with CpG oligonucleotides (Giuliani et al., 2006).
g. Immunization Route
Intraperitoneal injection (i.p.)
2. BEXSERO
a. Product Name:
Meningococcal Group B Vaccine
b. Tradename:
BEXSERO
c. Manufacturer:
Novartis Vaccines and Diagnostics, Inc
d. CDC CVX code:
163
e. Type:
Subunit vaccine
f. Status:
Licensed
g. Location Licensed:
USA, Canada
h. Host Species for Licensed Use:
Human
i. Allergen:
Latex
j. Immunization Route
Intramuscular injection (i.m.)
k. Storage
Store at 2°C to 8°C (36°F to 46°F), do not freeze, and keep away from light.
l . Approved Age for Licensed Use
10 to 25 years of age.
m. Description
BEXSERO (Meningococcal Group B Vaccine) is a sterile, white, opalescent, suspension for intramuscular injection. Each 0.5 mL dose of BEXSERO is formulated to contain 50 micrograms each of recombinant proteins Neisserial adhesin A (NadA), Neisserial Heparin Binding Antigen (NHBA), and factor H binding protein (fHbp), 25 micrograms of Outer Membrane Vesicles (OMV), 1.5 mg aluminum hydroxide (0.519 mg of Al3+), 3.125 mg sodium chloride, 0.776 mg histidine, and 10 mg sucrose at pH 6.4 – 6.7.(FDA: BEXSERO)
Vaccination Protocol:
Rat pups, aged 5 or 6 days, were injected i.p. with 100 μl of sera ( from immunized mice) previously diluted 1:10 and ferric dextran (Carmenate et al., 2004).
Challenge Protocol:
One hour after immunization, infant rats were challenged with 10^7 cfu of meningococcal strain Z4181. The development of bacteremia was assessed by culturing the blood samples taken 4 h after challenge (Carmenate et al., 2004).
Efficacy:
Sera of the challenge group of mice immunized with CCPS-P64kR showed a three-fold higher bactericidal response than the sera of the group immunized with the plain CCPS and they were able to protect against challenge with Neisseria meningococci in the infant rat protection model (Carmenate et al., 2004).
h.
Mouse Response
Host Strain:
BALB/c
Vaccination Protocol:
Two experiments were carried out; in both cases mice were immunized with 2.5 μg of either plain or conjugated CCPS, and Al(OH)3 as adjuvant. Two doses were given 15 days apart and 7 days after the last dose mice were bled, sera were stored at −20°C. In the first experiment four groups of 10 mice each were immunized with the following immunogens: CCPS–P64kR, CCPS–P64kC, carrier protein P64k, and plain polysaccharide. For the second experiment, four groups of 10 mice each were immunized with the three conjugates obtained from different size polysaccharides using the reductive amination method and with plain CCPS as control (Carmenate et al., 2004).
Challenge Protocol:
Sera of immunized mice was used in rats to detect an immune response (Carmenate et al., 2004).
Efficacy:
Sera of the challenge group immunized with CCPS-P64kR showed a three-fold higher bactericidal response than the sera of the group immunized with the plain CCPS and they were able to protect against challenge with Neisseria meningococci in the infant rat protection model (Carmenate et al., 2004).
4. Menactra
a. Product Name:
Meningococcal Polysaccharide (Serogroups A, C, Y and W-135) Diphtheria Toxoid Conjugate Vaccine
Cultured on Mueller Hinton agar and grown in Watson Scherp media. The polysaccharides are extracted from the N meningitidis cells and purified by centrifugation, detergent precipitation, alcohol precipitation, solvent extraction and diafiltration (FDA: Menactra).
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store at 2° to 8°C (35° to 46°F). DO NOT FREEZE.
n . Approved Age for Licensed Use
2-55 years of age.
o. Contraindication
This vaccine should not be administered to anyone with known hypersensitivity to any component of Menactra vaccine including diphtheria toxoid, or a life-threatening reaction after previous administration of a vaccine containing similar components (FDA: Menactra).
p. Description
Contains Neisseria meningitidis serogroup A, C, Y and W-135 capsular polysaccharide antigens individually conjugated to diphtheria toxoid protein. Menactra vaccine is not indicated for immunization against diphtheria (FDA: Menactra).
q.
Human Response
Immune Response:
Clinical studies reported antibodies were seen in 90-100% of those who were vaccinated with Menactra (FDA: Menactra).
Side Effects:
Side effects of vaccination include: injection site reactions, headache, fatigue, irritability and fever.
5. MenHibrix
a. Product Name:
Meningococcal Groups C and Y and Haemophilus b Tetanus Toxoid Conjugate Vaccine
Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens and Haemophilus b capsular polysaccharide (polyribosyl-ribitol-phosphate [PRP]) (FDA: MenHibrix).
Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined
k. Preparation
MEMOMUNE is cultivated with Mueller Hinton agar and Watson Scherp media and is freeze-dried with the group-specific polysaccharide antigens from Neisseria meningitidis, Group A, Group C, Group Y and Group W-135 (FDA: Menomune– A/C/Y/W-135).
l. Immunization Route
subcutaneous injection
m. Storage
Store the freeze-dried vaccine and reconstituted vaccine, when not in use, at 2° to 8°C (35° to 46°F).
n . Approved Age for Licensed Use
2 years of age and older
o. Contraindication
Individuals with known sensitivity to thimerosal or any other component of the vaccine.
p. Description
Meningococcal Polysaccharide Vaccine, Groups A, C, Y and W-135 Combined, is indicated for active immunization against invasive meningococcal disease caused by these serogroups (FDA: Menomune– A/C/Y/W-135).
q.
Human Response
Immune Response:
Measurable levels of antibodies against the group A and C polysaccharides decrease markedly during the first 3 years following a single dose of vaccine (FDA: Menomune– A/C/Y/W-135).
Side Effects:
Side effects of vaccination include: pain and redness of injection site, fever and/or headache (FDA: Menomune– A/C/Y/W-135).
Efficacy:
The serogroup A polysaccharide induces and antibody response in children as young as 3 months of age, the serogroup C component can be poorly immunogenic in recipients who are less than 18 to 24 months of age 5. The serogroups A and C have demonstrated estimated clinical efficacies of 85% to 100% in older children and adults. Serogroups Y and W-135 polysaccharides are safe and immunogenic in adults and in children greater than 2 years of age (FDA: Menomune– A/C/Y/W-135).
10. Menveo
a. Product Name:
Meningococcal (Groups A, C, Y and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine
N. meningitidis serogroup A, C, Y and W-135 oligosaccharides conjugated individually to Corynebacterium diphtheriae CRM197 protein (FDA: Menveo).
k. Preparation
The polysaccharides are produced by bacterial fermentation of N. meningitidis (serogroups A, C, Y or W-135). N. meningitidis strains A, C, Y and W-135 are each cultured and grown on Franz Complete medium and treated with formaldehyde. MenA, MenW-135 and MenY polysaccharides are purified by several extraction and precipitation steps. MenC polysaccharide is purified by a combination of chromatography and precipitation steps. The protein carrier (CRM197) is produced by bacterial fermentation and is purified by a series of chromatography and ultrafiltration steps. C. diphtheriae is cultured and grown on CY medium containing yeast extracts and amino acids. The oligosaccharides are prepared for conjugation from purified polysaccharides by hydrolysis, sizing, and reductive amination. After activation, each oligosaccharide is covalently linked to the CRM197 protein. The resulting glycoconjugates are purified to yield the four drug substances, which compose the final vaccine (FDA: Menveo).
l. Immunization Route
Intramuscular injection (i.m.)
m. Storage
Store refrigerated, away from the freezer compartment, at 36°F to 46°F (2°C to 8°C). Keep away from light (FDA: Menveo).
n . Approved Age for Licensed Use
MENVEO is approved for use in persons 11 to 55 years of age (FDA: Menveo).
o. Description
MENVEO [Meningococcal (Groups A, C, Y and W-135) Oligosaccharide Diphtheria CRM197 Conjugate Vaccine] is a sterile liquid vaccine administered by intramuscular injection that contains N. meningitidis serogroup A, C, Y and W-135 oligosaccharides conjugated individually to Corynebacterium diphtheriae CRM197 protein (FDA: Menveo).
Immune Response:
Mice immunized with P3A DNA produced an anti-MCPS IgM antibody response that was significantly higher (P < 0.05) than that of mice immunized with P3C DNA (negative control) (Prinz et al., 2003).
Efficacy:
Mice immunized with P3A DNA were protected against meningococcal infection, with 100% survival. Five of the six mice immunized with P3C DNA (negative control) died within 24 hr postchallenge (Prinz et al., 2003).
Vaccination Protocol:
To examine the protective efficacy of recombinant proteins, adult mice (6-week-old, female BALB/c animals, 35 per group) were immunised on days 1 and 21 with 25 μg of antigen given by subcutaneous (s.c.) injection. Each protein was mixed with Freund's incomplete adjuvant (50% v/v) prior to administration. Mice in control groups were immunised with adjuvant alone or recombinant homologous PorA prior to challenge (Sun et al., 2005).
Challenge Protocol:
28 days after immunization, animals were challenged with live bacteria at either a high (10^7 CFU, 15 mice) or low (10^6 CFU, 15 mice) dose of MC58 (Sun et al., 2005).
Efficacy:
ExbB, which is required for iron acquisition, elicited protective immunity and was able to protect mice from bacterial challenge (Sun et al., 2005).
Vaccination Protocol:
To examine the protective efficacy of recombinant proteins, adult mice (6-week-old, female BALB/c animals, 35 per group) were immunised on days 1 and 21 with 25 μg of LctP given by subcutaneous (s.c.) injection. Each protein was mixed with Freund's incomplete adjuvant (50% v/v) prior to administration. Mice in control groups were immunised with adjuvant alone or recombinant homologous PorA prior to challenge (Sun et al., 2005).
Challenge Protocol:
28 days after immunization, animals were challenged with live bacteria at either a high (10^7 CFU, 15 mice) or low (10^6 CFU, 15 mice) dose of MC58 (Sun et al., 2005).
Efficacy:
LctP which is required for iron acquisition, elicited protective immunity and was able to protect mice from bacterial challenge (Sun et al., 2005).
Vaccination Protocol:
Groups of mice were injected three times at 3-wk intervals with 10 or 20 μg of affinity-purified NspA recombinant protein and 25 μg of QuilA (CedarLane Laboratories, Hornby, Ontario, Canada) as the adjuvant. Control mice were injected with either 20 μg of BSA (Sigma), concentrated E. coli BL21(DE3) supernatant, or PBS. 2 wk after the third injection the mice were used for the protection experiments (Martin et al., 1997).
Challenge Protocol:
For inoculation of mice, meningococci were removed from the chocolate agar plates after ∼20 h of incubation and suspended in PBS and injected into mice (Martin et al., 1997).
Efficacy:
80% of the mice immunized with three injections of either 10 or 20 μg of purified recombinant meningococcal NspA protein survived the bacterial challenge comparatively to 0 to 20% in the control groups. Survivors at 72 h did not succumb during an additional two weeks of observation. The mice in the control group injected with concentrated E. coli culture supernatant were not protected against the bacterial challenge indicating that the components present in the culture media and other E. coli antigens that might be present in small amounts after purification do not contribute to the observed protection against N. meningitidis (Martin et al., 1997).
Description:
Vaccines were prepared with an equal volume of either Freund's complete adjuvant (first immunization) or Freund's incomplete adjuvant (subsequent immunizations) (West et al., 2001).
Description:
Vaccines were prepared with an equal volume of either Freund's complete adjuvant (first immunization) or Freund's incomplete adjuvant (subsequent immunizations) (West et al., 2001).
h. Immunization Route
subcutaneous injection
i.
Mouse Response
Host Strain:
NIH
Vaccination Protocol:
Each mouse received 0.2 ml, containing 10 μg of rTbpA protein and Freund's complete adjuvant, by subcutaneous injection. All animals were immunized on days 1, 21, and 28 (West et al., 2001).
Challenge Protocol:
Mice were infected by intraperitoneal injection of N. meningitidis at several challenge doses (West et al., 2001).
Efficacy:
100% protection was afforded by vaccination with rTbpA at the 2 × 10^7 CFU challenge dose andat the 2 × 10^8 CFU challenge dose, the rTbpA-vaccinated group had an 85% survival rate (West et al., 2001).
Vaccination Protocol:
Groups of 48 mice were immunized subcutaneously on days 0, 21, and 35 with different vaccine preparations containing 5 mg of protein adsorbed onto 0.1 mg of aluminum hydroxide per 0.5 ml; PBS containing aluminum hydroxide and heat-inactivated N. meningitidis B16B6 were used as controls (Lissolo et al., 1995).
Challenge Protocol:
41 days after immunization, mice within a group were subdivided into groups of eight, and each subgroup received by the intraperitoneal route 24 mg of iron-loaded hTf (Sigma) and, immediately after by the intraperitoneal route, 0.5 ml of N. meningitidis grown under iron restriction. The bacterial load varied from 10^4 to 10^8 CFU. Mortality rates were measured for 5 days following challenge (Lissolo et al., 1995).
Efficacy:
Mice immunized with purified Tbp2 survived a lethal challenge to a similar degree as animals immunized with the Tbp1-Tbp2 complex, demonstrating that Tbp2 played an important role in the protective activity observed with the complex, eliciting antibodies that are not only bactericidal but also inhibitory for meningococcal growth (Lissolo et al., 1995).
Meningococcal polysaccharide groups A, C, W-135 and Y conjugate vaccine
b. Tradename:
NIMENRIX
c. Manufacturer:
Pfizer Inc.
d. Type:
Conjugate vaccine
e. Status:
Licensed
f. Location Licensed:
Canada
g. Host Species for Licensed Use:
Human
h. Immunization Route
Intramuscular injection (i.m.)
i. Storage
Store at 2°C to 8°C (36°F to 46°F), do not freeze, and protect from light.
j . Approved Age for Licensed Use
1 to 55 years of age.
k. Description
NIMENRIX® (meningococcal polysaccharide groups A, C, W-135 and Y conjugate vaccine) is a tetravalent meningococcal polysaccharide conjugated vaccine consisting of Neisseria meningitidis capsular polysaccharides A, C, W-135 and Y each coupled to tetanus toxoid as a carrier protein. The Neisseria meningitidis serogroups A and C polysaccharides are conjugated with an adipic dihydrazide (AH) spacer and indirectly conjugated to the tetanus toxoid whereas the W-135 and Y polysaccharides are conjugated directly to tetanus toxoid. (Pfizer: NIMENRIX)
21. TRUMENBA
a. Product Name:
Meningococcal Group B Vaccine
b. Tradename:
TRUMENBA
c. Manufacturer:
Pfizer Inc.
d. Type:
Subunit vaccine
e. Status:
Licensed
f. Location Licensed:
USA
g. Host Species for Licensed Use:
Human
h. Immunization Route
Intramuscular injection (i.m.)
i. Storage
Store at 2°C to 8°C (36°F to 46°F), do not freeze.
j . Approved Age for Licensed Use
10 to 25 years of age.
k. Description
Trumenba is a sterile suspension composed of two recombinant lipidated factor H binding protein (fHBP) variants from N. meningitidis serogroup B, one from fHBP subfamily A and one from subfamily B (A05 and B01, respectively). The proteins are individually produced in E. coli. Production strains are grown in defined fermentation growth media to a specific density. The recombinant proteins are extracted from the production strains and purified through a series of column chromatography steps. Polysorbate 80 (PS80) is added to the drug substances and is present in the final drug product. (FDA: TRUMENBA)
IV. References
1. Carmenate et al., 2004: Carmenate T, Canaán L, Alvarez A, Delgado M, González S, Menéndez T, Rodés L, Guillén G. Effect of conjugation methodology on the immunogenicity and protective efficacy of meningococcal group C polysaccharide-P64k protein conjugates. FEMS immunology and medical microbiology. 2004; 40(3); 193-199. [PubMed: 15039094].
2. Comanducci et al., 2002: Comanducci M, Bambini S, Brunelli B, Adu-Bobie J, Aricò B, Capecchi B, Giuliani MM, Masignani V, Santini L, Savino S, Granoff DM, Caugant DA, Pizza M, Rappuoli R, Mora M. NadA, a novel vaccine candidate of Neisseria meningitidis. The Journal of experimental medicine. 2002; 195(11); 1445-1454. [PubMed: 12045242].
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