Beruflich Dokumente
Kultur Dokumente
Darja Kanduc*
Abstract Aims: Measles virus (MV) infection induces a protective immunity that
is accompanied by a transient pathologic suppression of the immune system. This
immunologic paradox remains unexplained in spite of the numerous hypotheses that have
been advanced (i.e., cytokine production, soluble immunosuppressive factor, cell cycle
block, signaling lymphocyte activation molecule receptor and MV infection of dendritic
cells, among others). Methods: Searching for molecular link(s) between MV infection and
host immunodeficiency, this study used the Immune Epitope DataBase to analyze the
peptide sharing between the antigenic MV hemagglutinin (H) protein and human proteins
associated with immunodeficiency. Results: It was found that the majority of MVH derived
epitopes share several exact pentapeptide sequences with numerous human proteins
involved in immune functions and immunodeficiency, such as B- and T-cell antigens,
and complement components. Conclusion: The data suggest that crossreactivity might
contribute to our understanding of the link between MV immunogenicity and MV-induced
immunosuppression, and highlight peptides unique to MV as a basis for developing effective
and safe anti-MV vaccines.
Measles virus (MV) infection and, to a lesser extent, anti-MV vaccination induce a protective Keywords
immune response associated with a transient immunosuppression that is the major cause of the immunodeficiency-
current high morbidity and mortality rate associated with MV disease[13] . associated proteins
The relationship between measles infection/vaccination and the decay of the immune function MVH-derived epitopes
has been the object of intensive investigations[15] . The timing of the immunosuppression appears MV immunogenicity
to be related to the antibody production in an infected individual[2] , as also indicated by the fact MV-induced
that antibody-dependent enhancement of MV infection in mouse and human macrophages has immunosuppression
been described[6] . Moreover, induction of maturation of dendritic cell (DC) precursors with both peptide crossreactivity
MV vaccine and wild-type strains is accompanied by a negative DC signaling to inhibit lymphocyte peptide sharing
proliferation that contributes to MV-induced lymphopenia[7] .
Many molecular events appear to be involved, for example, downregulation of IL-12 production[8] ;
interference with induction of alpha/beta IFN production[9] ; abnormal differentiation of CD40
ligand-activated human DCs[10] . Receptor usage may also contribute to MV-induced lymphopenia
and immunosuppression[11] . Wild-type MV propagates by using signaling lymphocyte activation
molecule (also called CD150) in lymphoid organs and nectin-4 in epithelial tissues, while MV vaccine
uses a complement-regulatory molecule, CD46, as a receptor[1115] . In addition, it is known that the
complex of MV fusion (F) and H glycoproteins induces immunosuppression invitro[16] . The MV F-H
complex silences T cells by activating cellular sphingomyelinases in a contact-dependent manner, thus
interfering with signaling pathways essential for T-cell activation[17,18] . Finally, it has to be considered
*Department of Biosciences, Biotechnologies & Biopharmaceutics, University of Bari, Bari, Italy; dkanduc@gmail.com part of
10.2217/FMB.14.137 2015 Future Medicine Ltd Future Microbiol. (2015) 10(4), 503515 ISSN 1746-0913 503
Research ArticleKanduc
that anti-MV antibodies (Abs) are present life- a well-known antigenic and immunogenic
long, whereas immune suppression is only tran- MV protein[3336] have been here explored
sient. With respect to this point, de Swarts lab[19] for pentapeptide sharing with human proteins
performed in vivo studies in macaques and found associated with immunodeficiency. Data are
that following initial MV-induced lymphopenia, reported showing that MVH-derived epitopes
lymphocyte counts rapidly return to normal after are mostly formed by peptide fragments also pre-
clearance of the virus, thus posing the question of sent in human proteins associated with immuno-
why immune suppression then lasts several weeks deficiency and immune system, thus suggesting
to months. The authors concluded that MV that MVH-derived epitopes have the potential
infection wipes out immunological memory, leav- to induce crossreactions with human proteins
ing individuals susceptible to opportunistic infec- involved in immune system functions.
tious agents that would normally be controlled by
the immune system[19] . Overall, it appears that Methods
measles-associated immunosuppression is a mul- The analyzed MVH-derived epitopes were
tifactorial phenomenon with an immune response retrieved from the Immune Epitope Database
that is diversified and dislocated intime. (IEDB [37]) [38] . At the time of the analysis,
In the present study, the potential role of viral IEDB contained 174 MVH-derived epitopes
versus human immune crossreactivity was ana- from different strains and with different char-
lyzed. Since 2000, reports from this lab have acteristics. Specifically, the database contained
described a massive peptide sharing between MVH epitopes linear or conformational in the
microbial and human proteins[2024] . The structure; of different lengths (up to 32 amino
data suggested that peptide crossreactivity may acids [aa]); validated as negative, positive or
underlie the pathological nexus between the had produced mixed negative/positive results
human host and infectious agents. Indeed, when in immunoassays; validated in different hosts.
bacterial/viral agents share epitopic sequences This study focused on linear epitopes that were
with host proteins, an immune response against derived from MVH protein (UniProtKB/Swiss-
the pathogen may result in humoral and/or cel- Prot entry: Q9IC33_MEASZ, 617aa)[39] from
lular crossreactions able to hit and damage the strain EdmonstonZagreb vaccine (or subacute
host components[2529] . Actually the crossreac- sclerose panencephalitis virus, NCBI Taxonomic
tivity scenario is of extreme relevance in light of identifier: 70149); that were not longer than 15
two factors: first, the dimension of the peptide aa; and that had been experimentally tested
sharing between pathogens and the human pro- as positive in the human host. Based on these
teome (>90%)[21,22] and, second, the notion that selection criteria, 73 MVH-derived epitopes
a 5-amino acid grouping plays a basic role in were found and analyzed. Each epitope was dis-
antigen-antibody recognition and in humoral/ sected into overlapping pentapeptides offset by
cellular immune reactivity[3032] . Indeed, the one residue each other (i.e.,MSPQR, SPQRD,
massive pathogen versus human pentapeptide PQRDR, QRDRI and RDRIN, among others).
overlap and the fact that a pentapeptide is suf- Next, each viral pentamer was analyzed for
ficient to evoke an immune response mean that occurrence(s) within a library containing pri-
immune reactions following infections may be mary sequences of human proteins involved in
a considerable source of crossreactions. immune functions and immunodeficiency. The
In this scientific framework, the present study human protein library was randomly derived
poses the question: may MV versus human pep- from UniProtKB Database[39,40] , utilizing
tide overlap represent a link between immune immune system, immunodeficiency and Homo
response and immunosuppression in MV sapiens as keywords. The keyword-guided search
infection? Since protective anti-MV immune produced a list of 1793 proteins that are syntheti-
responses and pathologic immunosuppression cally described in Supplementary Table 1 (see online
are temporally related following MV infec- at www.futuremedicine.com/doi/suppl/10.2217/
tion[17] , it seemed logical to hypothesize that fmb.14.137). Human proteins are reported as
viral epitopic sequences targeted by the immune UniProtKB/Swiss-Prot entry names throughout
system might contain the key to understand the the paper, unless when discussed in detail.
MV infection-induced immunosuppression. To identify peptide motifs unique to MVH
Following this rationale, experimentally vali- protein, each MVH pentapeptide was used as a
dated epitopes from MV hemagglutinin (MVH) probe to search the entire human proteome for
instances of the same pentapeptide using the proteins. The remaining 67 viral epitopes share
Protein International Resource (PIR) peptide peptides with human proteins crucially involved
match program[41] . MVH pentapeptides with no in the human defense system as complement pro-
matches to the human proteome were recorded. teins CO2, CO3, and CO6. Obviously, an anti-
MVH protein from Edmonston wild strain, MVH immune response crossreacting with CO2,
AF266288.2, NCBI Taxonomic identifier CO3 and CO6 might lead to deficiencies of such
11234[42] was used as a control in comparative complement proteins, thus predisposing individ-
sequence similarity analyses. Sequence align- uals to recurrent respiratory infections and infec-
ment of MVH protein from Edmonston vaccine tions caused by encapsulated organisms including
strain and the wild one was carried out by using Streptococcus pneumonia [53] . In addition, Table 1
ClustalW2 program[43] . shows that the peptide sharing involves cluster
differentiation (CD) antigens associated with
Results & discussion B- and T-cell development and maturation, such
Analysis of the peptide sharing between as CD14; CD1C; CD24; CD34; CD36; CD38;
MV-derived epitopes and human proteins related CD3D; CD5L; CD79B; CD8A; CD40L. As
to immunodeficiency was conducted on the viral regards this latter potential target of crossreac-
H protein since, as indicated by an ample litera- tions, CD40L, it is of note to recall that abnormal
ture[3336,44,45] , the MVH is a main target of the differentiation of CD40 ligand-activated human
humoral immune responses. The analysis used DCs is induced by MV[10] .
pentapeptides as scanning probes based on the Clinically, alterations in these CD molecules
validated concept that a grouping of five aa resi- have been involved in: immunodeficiency with
dues represents a quantum in immunorecogni- impairment of both humoral and cell-mediated
tion and immunoreactivity([31,32] and pertinent immunity, and consequent persistent infec-
references therein). Indeed, also T-cell epitopes, tions by opportunistic organisms (CD3D)[54] ;
canonically represented by peptides 915-aa long, recurrent bacterial and opportunistic infections,
consist of a core pentapeptide motif, which pro- including Pneumocystis carinii pneumonia and
vides the majority of the specific contacts, and of intractable diarrhea due to Cryptosporidium infec-
flanking residues, which determine the peptide tion (CD40L)[55] ; agammaglobulinemia with
binding potential[4651] . A paradigmatic exam- consequent severe infections in the first years of
ple of the crucial role exerted by small peptide life (CD79B)[56] ; immunologic defect leading to
modules in MV immunobiology is the MVH recurrent bacterial infections (CD8A)[57] .
pentapeptide IPRFK (aa position 473477) that In the scientific context of the present study,
constitutes an epitope recognized by the anti- the peptide sharing between MVH and the CD
MVH MAb E128[35] . Moreover, MVH protein antigens described above also offers a chance to
entirely lost its reactivity with MAb E128 when observe that CD molecules are spatially located
carrying aa substitutions at positions 473 to 477 on the surface of B or T cells, thus being highly
and the same pentapeptide region is involved in accessible to crossreactive attacks; in other
the interaction with CD46, a receptor for MV words, might de facto represent privileged targets
vaccine strains[52] . in immune crossreactions.
The overall picture of the pentapeptide overlap Table 1 also shows that, in many instances, the
between MVH-derived epitopes and immunode- peptide overlap is multiple. For example:
ficiency-associated proteins is reported in Table 1. AP3B1 shares pentapeptides DSESG, SLLDL
It can be seen that, numerically, 219 human pro- and TVELK (with SLLDL and TVELK
teins involved in the modulation and regulation repeated twice) with five MVH-derived B-cell
of immune functions share peptide sequences epitopes (see Table 1, IEDB IDs 42603, 39483,
with B- and T-cell MVH-derived epitopes. 23048, 39732 and 7279). Altered AP3B1 is
involved in an increased susceptibility to
Description of the potential peptide infections[58] ;
crossreactome between MVH
&immunodeficiency-associated proteins SHIP2 shares pentapeptides AAEEL and
A first, immediate datum that emerges from the FEVGV with three B-cell epitopes (IEDB IDs
analysis of Table 1 is that only six out of the selected 9929, 73483 and 56283) and one T-cell epitope
73 MVH epitopes are exempt from pentapeptide (IEDB ID 59787) for a total of four matches.
matches with the immunodeficiency-associated Alterations of SHIP2 are involved in
73 59483 SLSTNLDVtnsiehq B cell IFNA1 (SLSTNL) IFNA2 (SLSTNL) M3K3 (SLSTN) TRI11 (LSTNL) DUS6 (STNLDV) DUS7 (STNLDV)
83 58485 siEHQVKDVLtplfk B cell JAK1 (EHQVK) IFIT1 (HQVKD) KI20A (VKDVL) KIF5A (VKDVL) KINH (VKDVL) SCF (VKDVL)
93 65635 tplfKIIGDEVGLRT B cell PSME4 (KIIGD) ITB1 (IGDEVG) ASB16 (VGLRT)
101 8195 deVGLRTPQRFTdlv B cell ASB16 (VGLRT) MRC2 (GLRTP) IF16 (LRTPQ) TRI25 (PQRFT)
103 68723 VGLRTPQRFTdlvkf B cell ASB16 (VGLRT) MRC2 (GLRTP) IF16 (LRTPQ) TRI25 (PQRFT)
113 9319 dLVKFISDKIKFlnp B cell PDC6I (LVKFI) HERC2 (KFISD) PDIA3 (KFISDK) CATE (SDKIK) PPARG (DKIKF)
117 16290 FISDKIKFl T cell, HLA-A2 PDIA3 (FISDK) CATE (SDKIK) PPARG (DKIKF)
www.futuremedicine.com
373 7812 dDKLRMEtCFQQAck B cell SPN90 (DKLRME) RPGF1 (CFQQA)
383 52000 qqackgKIQALCENp B cell ASB6 (KIQAL) CATF (KIQAL) PO210 (KIQAL) TLR3 (KIQAL) DB127 (ALCEN)
MVH epitopes are hotspots for crossreactions with human immunodeficiency antigens
393 35050 lCENPEWAPLKDnri B cell CD5L (CENPE) SEM4A (NPEWA) ZEP2 (PEWAP) DNM3B (APLKD)
403 30220 kdnripSYGVLSVDL B cell CD36 (SYGVL) KS6A1 (SYGVL) UBR4 (GVLSV) BIRC1 (LSVDL) ITPR2 (LSVDL)
Amino acid position along the measles virus hemagglutinin sequence.
Epitope IEDB ID from[37].
Amino acid sequence given in one-letter code.
Pentapeptide sequence(s) shared with the human proteins associated with immunodeficiency given in capitals.
#
Further data and related references from[37].
Proteins given by UniProtKB/Swiss-Prot entry names.
In parentheses, shared pentapeptide(s) given in italic.
Proteins sharing two overlapped pentapeptides (e.g.,a hexapeptide) are given in bold.
Proteins sharing two pentapeptides are given underlined.
IEDB: Immune Epitope Database ; MVH: Measles virus hemagglutinin.
Research Article
507
508
Table 1. Peptide sharing between measles virus hemagglutinin-derived epitopes and human proteins associated with immunodeficiency (cont.).
Position IEDB ID Epitope sequence, Epitope immune context# Human immunodeficiency proteins sharing peptides with MVH,,,
411 23048 GVLSVDLSLTVELKi B cell UBR4 (GVLSV) BIRC1 (LSVDL) ITPR2 (LSVDL) PPARG (SVDLS) TSC2 (SVDLS) CDN1A (VDLSL) STAT2
(SLTVE) AP3B1 (TVELK) CD8A (TVELK)
413 39732 LSVDLSLTVELKIKI B cell BIRC1 (LSVDL) ITPR2 (LSVDL) PPARG (SVDLS) TSC2 (SVDLS) CDN1A (VDLSL) STAT2 (SLTVE) AP3B1
(TVELK) CD8A (TVELK) KPCE (LKIKI)
421 68272 veLKIKIASGFgpli B cell KPCE (LKIKI) ATM (KIASGF)
423 36890 LKIKIASGFgplith B cell KPCE (LKIKI) ATM (KIASGF)
433 48370 pLITHGSGMDLYKSn B cell GLGB (LITHG) AL14E (SGMDL) OAS2 (DLYKS) SC24D (DLYKS)
443 40826 lyksnhnnVYWLTIp B cell TEN1 (VYWLTI)
453 72808 wLTIPPmKNLALGVi B cell SKIV2 (LTIPP, ALGVI) ZEP2 (LTIPP) NCKP1 (KNLAL) RPC2 (KNLAL) UBA3 (KNLAL) RAD50 (NLALG)
Research ArticleKanduc
immunosuppression lasting several weeks to aspects of the MV immunology, the high level
months[19] . That is, the most immediate effects of viral load variability that may characterize
of crossreactivity would be lymphopenia and, infected individuals, the concomitant factors that
contemporaneously, decrease of the viral antigen may favor the immunodeficienty phenomenon
load, which would allow MV-specific lymphocyte (e.g.,malnourishment, other infections) need to
expansion and restore the functioning of immu- be considered[15] . Finally, it has to be noted that
notolerance mechanisms in the course of weeks the present MVH analysis is not exhaustive of the
to months, with a progressive disappearance of viral versus human crossreactivity potential and
the immunosuppression status. other MV proteins may also play an important
It is mandatory to underline the speculative role. As mentioned earlier in this paper, numerous
aspect of the observations offered in the above factors appear to be involved in determining the
discussion. Likewise, again it has to be stressed MV-induced immunosuppression[618] . However,
that the factors at play in the modulation of given these caveats, the vast pentapeptide over-
MV-induced immune responses form a complex lap between MVH-derived epitopes and immu-
picture. For example, it has to be mentioned that nodeficiency-related antigens warrants further
there is an association of CD46, signaling lym- experimental research in order to understand and
phocyte activation molecule and CD209 cellular define a possible contribution of crossreactivity to
receptor gene single nucleotide polymorphisms MV-induced immunosuppression.
with variations in MV vaccine-induced immune
responses [70] , and a single aa change in the H Searching for an anti-MV vaccine: MVH
protein (namely, N481Y) may alter its ability to identity spots at the pentapeptide level
bind CD46[71] . Moreover, the scientific-clinical This study might also offer approaches toward
complexity of the MV infection, the not yet clear the formulation of anti-MV vaccines based on
Table 2. Measles virus hemagglutinin amino acid sequence from Edmonston vaccine and wild strains:conservation of the
epitope sharing with immunodeficiency-related antigens.
Strain Location of epitopic sequences,, Amino acid
position
A MSPQRDRINAFYKDNPHPKGSRIVINREHLMIDRPYVLLAVLFVMFLSLIGLLAIAGIRL 60
B MSPQRDRINAFYKDNPHPKGSRIVINREHLMIDRPYVLLAVLFVMSLSLIGLLAIAGIRL 60
A HRAAIYTAEIHKSLSTNLDVTNSIEHQVKDVLTPLFKIIGDEVGLRTPQRFTDLVKFISD 120
B HRAAIYTAEIHKSLSTNLDVTNSIEHQVKDVLTPLFKIIGDEVGLRTPQRFTDLVKFISD 120
A KIKFLNPDREYDFRDLTWCINPPERIKLDYDQYCADVAAEELMNALVNSTLLETRTTNQF 180
B KIKFLNPDREYDFRDLTWCINPPERIKLDYDQYCADVAAEELMNALVNSTLLETRTTNQF 180
A LAVSKGNCSGPTTIRGQFSNMSLSLLDLYLGRGYNVSSIVTMTSQGMYGGTYLVEKPNLS 240
B LAVSKGNCSGPTTIRGQFSNMSLSLLDLYLSRGYNVSSIVTMTSQGMYGGTYLVEKPNLS 240
A SKRSELSQLSMYRVFEVGVIRNPGLGAPVFHMTNYLEQPASNDLSNCMVALGELKLAALC 300
B SKRSELSQLSMYRVFEVGVIRNPGLGAPVFHMTNYLEQPVSNDLSNCMVALGELKLAALC 300
A HGEDSITIPYQGSGKGVSFQLVKLGVWKSPTDMQSWVPLSTDDPVIDRLYLSSHRGVIAD 360
B HGEDSITIPYQGSGKGVSFQLVKLGVWKSPTDMQSWVPLSTDDPVIDRLYLSSHRGVIAD 360
A NQAKWAVPTTRTDDKLRMETCFQQACKGKIQALCENPEWAPLKDNRIPSYGVLSVDLSLT 420
B NQAKWAVPTTRTDDKLRMETCFQQACKGKIQALCENPEWAPLKDNRIPSYGVLSVDLSLT 420
A VELKIKIASGFGPLITHGSGMDLYKSNHNNVYWLTIPPMKNLALGVINTLEWIPRFKVSP 480
B VELKIKIASGFGPLITHGSGMDLYKSNHNNVYWLTIPPMKNLALGVINTLEWIPRFKVSP 480
A YLFNVPIKEAGEDCHAPTYLPAEVDGDVKLSSNLVILPGQDLQYVLATYDTSRVEHAVVY 540
B NLFTVPIKEAGEDCHAPTYLPAEVDGDVKLSSNLVILPGQDLQYVLATYDTSRVEHAVVY 540
A YVYSPGRSFSYFYPFRLPIKGVPIELQVECFTWDQKLWCRHFCVLADSESGGHITHSGMV 600
B YVYSPGRSFSYFYPFRLPIKGVPIELQVECFTWDQKLWCRHFCVLADSESGGHITHSGMV 600
A GMGVSCTVTREDGTNRR 617
B GMGVSCTVTREDGTNRR 617
Measles virus hemagglutinin from (A) vaccine and (B) wild strains; further details are provided in Methods section.
Primary measles virus hemagglutinin sequences were aligned using CLUSTAL 2.1 sequence alignment program[43].
Sequences relative to the epitopic peptide sharing found with vaccine strain (see Table 1) are underlined.
Table 3. Pentapeptides uniquely owned by measles virus hemagglutinin and absent in the
human proteome.
Amino acid position, Pentapeptide,
10 AFYKD
25 INREH
28 EHLMI
32 IDRPY
34 RPYVL
136 LTWCI
137 TWCIN
138 WCINP
226 GMYGG
248 QLSMY
251 MYRVF
268 PVFHM
269 VFHMT
270 FHMTN
271 HMTNY
274 NYLEQ
308 IPYQG
326 VWKSP
332 DMQSW
361 NQAKW
370 TRTDD
378 METCF
384 QACKG
398 EWAPL
440 GMDLY
444 YKSNH
445 KSNHN
449 NNVYW
450 NVYWL
453 WLTIP
472 WIPRF
473 IPRFK
491 GEDCH
526 LATYD
539 VYYVY
555 FRLPI
567 QVECF
569 ECFTW
570 CFTWD
575 QKLWC
578 WCRHF
581 HFCVL
Measles virus hemagglutinin pentapeptides from Edmonston vaccine and wild strains were analyzed for matches in the human
proteome using PIR peptide match program[39,65].
Consecutively overlapping pentapeptides and related amino acid positions given in bold.
peptides unique to the virus and absent in the entire human proteome highlights that 42 penta-
human host. Indeed, a pentapeptide matching peptides are unique to the viral protein from both
analysis of MVH primary sequence versus the Edmonston vaccine and wild strains, and have no
counterparts in the human proteins. This set of of measles might be at hand[7274] without the
unique peptide motifs represents the molecular toll of adverse collateral events[75,76] .
signature of MVH and is described in Table 3.
Possibly vaccines based on such unique pep- Conclusion
tides might guarantee a high anti-MV specific- The present study describes a wide peptide
ity and, theoretically, no crossreactivity in vac- sharing between MVH-derived epitopes and
cinees, thus also allowing repeated and multiple human immunodeficiency-associated pro-
vaccinations in order to render permanent the teins, advances the hypothesis that immune
anti-MV immunization status. Interestingly, a responses against MV may cross-react with
few unique pentapeptides consecutively over- molecules crucially involved in the host immune
lap, thus forming longer peptide stretches that function, and delineates cross-reactivity as a
might be particularly useful in anti-MV vaccine molecular mechanism able to explain the still
formulations (i.e.,LTWCINP, PVFHMTNY, obscure MV-induced immunosuppression. The
YKSNHN, NNVYWL; Table 3, aa sequences data not only offer a key to understanding the
in bold). Perhaps the goal of global eradication adverse events associated with MV infection and
Executive summary
The scientific problem
Powerful anti-measles virus (MV) immune responses follow MV infection and evoke a lifelong immunity, and, at the
same time, also cause a transient immunosuppression status that can lead to secondary, often fatal, infections.
The molecular mechanism(s) underlying the immunoprotective and immunosuppressive aspects of anti-MV immune
response remain obscure.
This paper describes a vast peptide platform shared between MV hemagglutinin derived epitopes and human proteins
associated with immunodeficiency, thus suggesting that peptide crossreactivity might be a factor contributing to the
establishment of the immunosuppression status.
Crossreactivity might explain why anti-MV antibodies are present lifelong whereas immune suppression is only
transient. Indeed, while anti-MV antibodies pertain to the protective action of the immune system (so that they must
be preserved and can last lifelong), instead a response crossreacting with self molecules (such as B- and T-cell antigens,
complement proteins and other immunodeficiency-related proteins) breaks immunotolerance mechanisms and must
be deleted in the short-long term (weeks to months).
The clinical problem
Vaccines are available against measles, a viral respiratory disease that is highly contagious and highly widespread.
However, the success of the MV vaccine is a datum of fact in Western countries only.
According to CDC[77], MV is still a common and often fatal disease in developing countries, with 20 million cases and
164,000 deaths each year worldwide.
A tight vaccination coverage is necessary and new anti-MV vaccine strategies not potentially burdened by possible
collateral immunosuppressive effects are needed.
The peptide commonality between MV hemagglutinin derived epitopes and human proteins associated with
immunodeficiency might help understand how immunosuppression is caused by MV and might help design new
anti-MV immunotherapies based on peptides unique to MV and not shared with proteins of the human host.
Future perspective
The present study offers a key to understand the immunosuppression associated with MV infection/vaccination and
proposes a methodology to construct safe and effective vaccines against MV. More in general, the peptide uniqueness
concept might be applied to define a proper vaccinology for the numerous (re)emerging infectious diseases. Replacing
entire antigens from infectious agents with specific peptides unique to the antigens would reduce the potential
crossreactivity risk, control the collateral adverse events, and, as well, confer effectiveness to vaccination. In a future
perspective, the present study represents a viable way for the global eradication of infectious diseases.
anti-MV vaccination protocols, but also propose interest in or financial conflict with the subject matter or
peptide uniqueness as a concept for developing materials discussed in the manuscript. This includes
safe and effective vaccines against MV. employment, consultancies, honoraria, stock ownership or
options, expert testimony, grants or patents received or
Future perspective pending, or royalties.
The results exposed here may lead to the devel- No writing assistance was utilized in the production of
opment of anti-MV vaccines based on specific this manuscript.
peptides unique to MV antigens. Such vaccines
would confer effectiveness to vaccination, elimi- Ethical conduct of research
nate the potential cross-reactivity risk, and allow The author states that they have obtained appropriate
repeated and safe vaccination campaigns, thus institutional review board approval or have followed the
providing a viable way for the eradication of MV. principles outlined in the Declaration of Helsinki for all
human or animal experimental investigations. In addi-
Financial & competing interests disclosure tion, for investigations involving human subjects,
The author has no relevant affiliations or financial involve- informed consent has been obtained from the participants
ment with any organization or entity with a financial involved.
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