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SARS-CoV-2 vaccines: What we know, what we can do to improve them and what we could learn from other well-known viruses

  • In recent weeks, the rate of SARS-CoV-2 infections has been progressively increasing all over the globe, even in countries where vaccination programs have been strongly implemented. In these regions in 2021, a reduction in the number of hospitalizations and deaths compared to 2020 was observed. This decrease is certainly associated with the introduction of vaccination measures. The process of the development of effective vaccines represents an important challenge. Overall, the breakthrough infections occurring in vaccinated subjects are in most cases less severe than those observed in unvaccinated individuals. This review examines the factors affecting the immunogenicity of vaccines against SARS-CoV-2 and the possible role of nutrients in modulating the response of distinct immune cells to the vaccination.

    Citation: Sirio Fiorino, Andrea Carusi, Wandong Hong, Paolo Cernuschi, Claudio Giuseppe Gallo, Emanuele Ferrara, Thais Maloberti, Michela Visani, Federico Lari, Dario de Biase, Maddalena Zippi. SARS-CoV-2 vaccines: What we know, what we can do to improve them and what we could learn from other well-known viruses[J]. AIMS Microbiology, 2022, 8(4): 422-453. doi: 10.3934/microbiol.2022029

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  • In recent weeks, the rate of SARS-CoV-2 infections has been progressively increasing all over the globe, even in countries where vaccination programs have been strongly implemented. In these regions in 2021, a reduction in the number of hospitalizations and deaths compared to 2020 was observed. This decrease is certainly associated with the introduction of vaccination measures. The process of the development of effective vaccines represents an important challenge. Overall, the breakthrough infections occurring in vaccinated subjects are in most cases less severe than those observed in unvaccinated individuals. This review examines the factors affecting the immunogenicity of vaccines against SARS-CoV-2 and the possible role of nutrients in modulating the response of distinct immune cells to the vaccination.



    In 1922, S. Banach [15] provided the concept of Contraction theorem in the context of metric space. After, Nadler [28] introduced the concept of set-valued mapping in the module of Hausdroff metric space which is one of the potential generalizations of a Contraction theorem. Let (X,d) is a complete metric space and a mapping T:XCB(X) satisfying

    H(T(x),T(y))γd(x,y)

    for all x,yX, where 0γ<1, H is a Hausdorff with respect to metric d and CB(X)={SX:S is closed and bounded subset of X equipped with a metric d}. Then T has a fixed point in X.

    In the recent past, Matthews [26] initiate the concept of partial metric spaces which is the classical extension of a metric space. After that, many researchers generalized some related results in the frame of partial metric spaces. Recently, Asadi et al. [4] introduced the notion of an M-metric space which is the one of interesting generalizations of a partial metric space. Later on, Samet et al. [33] introduced the class of mappings which known as (α,ψ)-contractive mapping. The notion of (α,ψ) -contractive mapping has been generalized in metric spaces (see more [10,12,14,17,19,25,29,30,32]).

    Throughout this manuscript, we denote the set of all positive integers by N and the set of real numbers by R. Let us recall some basic concept of an M-metric space as follows:

    Definition 1.1. [4] Let m:X×XR+be a mapping on nonempty set X is said to be an M-metric if for any x,y,z in X, the following conditions hold:

    (i) m(x,x)=m(y,y)=m(x,y) if and only if x=y;

    (ii) mxym(x,y);

    (iii) m(x,y)=m(y,x);

    (iv) m(x,y)mxy(m(x,z)mxz)+(m(z,y)mz,y) for all x,y,zX. Then a pair (X,m) is called M-metric space. Where

    mxy=min{m(x,x),m(y,y)}

    and

    Mxy=max{m(x,x),m(y,y)}.

    Remark 1.2. [4] For any x,y,z in M-metric space X, we have

    (i) 0Mxy+mxy=m(x,x)+m(y,y);

    (ii) 0Mxymxy=|m(x,x)m(y,y)|;

    (iii) Mxymxy(Mxzmxz)+(Mzymzy).

    Example 1.3. [4] Let (X,m) be an M-metric space. Define mw, ms:X×XR+ by:

    (i)

    mw(x,y)=m(x,y)2mx,y+Mx,y,

    (ii)

    ms={m(x,y)mx,y, if xy0, if x=y.

    Then mw and ms are ordinary metrics. Note that, every metric is a partial metric and every partial metric is an M-metric. However, the converse does not hold in general. Clearly every M-metric on X generates a T0 topology τm on X whose base is the family of open M -balls

    {Bm(x,ϵ):xX, ϵ>0},

    where

    Bm(x,ϵ)={yX:m(x,y)<mxy+ϵ}

    for all xX, ε>0. (see more [3,4,23]).

    Definition 1.4. [4] Let (X,m) be an M-metric space. Then,

    (i) A sequence {xn} in (X,m) is said to be converges to a point x in X with respect to τm if and only if

    limn(m(xn,x)mxnx)=0.

    (ii) Furthermore, {xn} is said to be an M-Cauchy sequence in (X,m) if and only if

    limn,m(m(xn,xm)mxnxm), and limn,m(Mxn,xmmxnxm)

    exist (and are finite).

    (iii) An M-metric space (X,m) is said to be complete if every M-Cauchy sequence {xn} in (X,m) converges with respect to τm to a point xX such that

    limnm(xn,x)mxnx=0, and limn(Mxn,xmxnx)=0.

    Lemma 1.5. [4] Let (X,m) be an M-metric space. Then:

    (i) {xn} is an M-Cauchy sequence in (X,m) if and only if {xn} is a Cauchy sequence in a metric space (X,mw).

    (ii) An M-metric space (X,m) is complete if and only if the metric space (X,mw) is complete. Moreover,

    limnmw(xn,x)=0 if and only if (limn(m(xn,x)mxnx)=0, limn(Mxnxmxnx)=0).

    Lemma 1.6. [4] Suppose that {xn} convergesto x and {yn} converges to y as n approaches to in M-metric space (X,m). Then we have

    limn(m(xn,yn)mxnyn)=m(x,y)mxy.

    Lemma 1.7. [4] Suppose that {xn} converges to xas n approaches to in M-metric space (X,m).Then we have

    limn(m(xn,y)mxny)=m(x,y)mxy for all yX.

    Lemma 1.8. [4] Suppose that {xn} converges to xand {xn} converges to y as n approaches to in M-metric space (X,m). Then m(x,y)=mxymoreover if m(x,x)= m(y,y), then x=y.

    Definition 1.9. Let α:X×X[0,). A mapping T:XX is said to be an α-admissible mapping if for all x,yX

    α(x,y)1α(T(x),T(y))1.

    Let Ψ be the family of the (c)-comparison functions ψ:R+{0}R+{0} which satisfy the following properties:

    (i) ψ is nondecreasing,

    (ii) n=0ψn(t)< for all t>0, where ψn is the n-iterate of ψ (see [7,8,10,11]).

    Definition 1.10. [33] Let (X,d) be a metric space and α:X×X[0,). A mapping T:XX is called (α,ψ)-contractive mapping if for all x,yX, we have

    α(x,y)d(T(x),T(x))ψ(d(x,y)),

    where ψΨ.

    A subset K of an M-metric space X is called bounded if for all xK, there exist yX and r>0 such that xBm(y,r). Let ¯K denote the closure of K. The set K is closed in X if and only if ¯K=K.

    Definition 1.11. [31] Define Hm:CBm(X)×CBm(X)[0,) by

    Hm(K,L)=max{m(K,L),m(L,K)},

    where

    m(x,L)=inf{m(x,y):yL} andm(L,K)=sup{m(x,L):xK}

    Lemma 1.12. [31] Let F be any nonempty set in M-metric space (X,m), then

    x¯F if and only if m(x,F)=supaF{mxa}.

    Proposition 1.13. [31] Let A,B,CCBm(X), then

    (i) m(A,A)=supxA{supyAmxy},

    (ii) (m(A,B)supxAsupyBmxy)(m(A,C)infxAinfzCmxz)+

    (m(C,B)infzCinfyBmzy).

    Proposition 1.14. [31] Let A,B,CCBm(X) followingare hold

    (i) Hm(A,A)=m(A,A)=supxA{supyAmxy},

    (ii) Hm(A,B)=Hm(B,A),

    (iii) Hm(A,B)supxAsupyAmxy)Hm(A,C)+Hm(B,C)infxAinfzCmxzinfzCinfyBmzy.

    Lemma 1.15. [31] Let A,BCBm(X) and h>1.Then for each xA, there exist at the least one yB such that

    m(x,y)hHm(A,B).

    Lemma 1.16. [31] Let A,BCBm(X) and l>0.Then for each xA, there exist at least one yB such that

    m(x,y)Hm(A,B)+l.

    Theorem 1.17. [31] Let (X,m) be a complete M-metric space and T:XCBm(X). Assume that there exist h(0,1) such that

    Hm(T(x),T(y))hm(x,y), (1.1)

    for all x,yX. Then T has a fixed point.

    Proposition 1.18. [31] Let T:XCBm(X) be a set-valued mapping satisfying (1.1) for all x,y inan M-metric space X. If zT(z) for some z in Xsuch that m(x,x)=0 for xT(z).

    We start with the following definition:

    Definition 2.1. Assume that Ψ is a family of non-decreasing functions ϕM:R+R+ such that

    (i) +nϕnM(x)< for every x>0 where ϕnM is a nth-iterate of ϕM,

    (ii) ϕM(x+y)ϕM(x)+ϕM(y) for all x,yR+,

    (iii) ϕM(x)<x, for each x>0.

    Remark 2.2. If αn|n= =0 is a convergent series with positive terms then there exists a monotonic sequence (βn)|n= such that βn|n== and αnβn|n==0 converges.

    Definition 2.3. Let (X,m) be an M-metric pace. A self mapping T:XX is called (α,ϕM)-contraction if there exist two functions α:X×X[0,) and ϕMΨ such that

    α(x,y)m(T(x),T(y))ϕM(m(x,y)),

    for all x,yX.

    Definition 2.4. Let (X,m) be an M-metric space. A set-valued mapping T:XCBm(X) is said to be (α,ϕM)-contraction if for all x,yX, we have

    α(x,y)Hm(T(x),T(x))ϕM(m(x,y)), (2.1)

    where ϕMΨ and α:X×X[0,).

    A mapping T is called α-admissible if

    α(x,y)1α(a1,b1)1

    for each a1T(x) and b1T(y).

    Theorem 2.5. Let (X,m) be a complete M-metric space.Suppose that (α,ϕM) contraction and α-admissible mapping T:XCBm(X)satisfies the following conditions:

    (i) there exist x0X such that α(x0,a1)1 for each a1T(x0),

    (ii) if {xn}X is a sequence such that α(xn,xn+1)1 for all n and {xn}xX as n, then α(xn,x)1 for all nN. Then T has a fixed point.

    Proof. Let x1T(x0) then by the hypothesis (i) α(x0,x1)1. From Lemma 1.16, there exist x2T(x1) such that

    m(x1,x2)Hm(T(x0),T(x1))+ϕM(m(x0,x1)).

    Similarly, there exist x3T(x2) such that

    m(x2,x3)Hm(T(x1),T(x2))+ϕ2M(m(x0,x1)).

    Following the similar arguments, we obtain a sequence {xn}X such that there exist xn+1T(xn) satisfying the following inequality

    m(xn,xn+1)Hm(T(xn1),T(xn))+ϕnM(m(x0,x1)).

    Since T is α-admissible, therefore α(x0,x1)1α(x1,x2)1. Using mathematical induction, we get

    α(xn,xn+1)1. (2.2)

    By (2.1) and (2.2), we have

    m(xn,xn+1)Hm(T(xn1),T(xn))+ϕnM(m(x0,x1))α(xn,xn+1)Hm(T(xn1),T(xn))+ϕnM(m(x0,x1))ϕM(m(xn1,xn))+ϕnM(m(x0,x1))=ϕM[(m(xn1,xn))+ϕn1M(m(x0,x1))]ϕM[Hm(T(xn2),T(xn1))+ϕn1M(m(x0,x1))]ϕM[α(xn1,xn)Hm(T(xn1),T(xn))+ϕn1M(m(x0,x1))]ϕM[ϕM(m(xn2,xn1))+ϕn1M(m(x0,x1))+ϕn1M(m(x0,x1))]ϕ2M(m(xn2,xn1))+2ϕnM(m(x0,x1))....
    m(xn,xn+1)ϕnM(m(x0,x1))+nϕnM(m(x0,x1))m(xn,xn+1)(n+1)ϕnM(m(x0,x1)).

    Let us assume that ϵ>0, then there exist n0N such that

    nn0(n+1)ϕnM(m(x0,x1))<ϵ.

    By the Remarks (1.2) and (2.2), we get

    limnm(xn,xn+1)=0.

    Using the above inequality and (m2), we deduce that

    limnm(xn,xn)=limnmin{m(xn,xn),m(xn+1,xn+1)}=limnmxnxn+1limnm(xn,xn+1)=0.

    Owing to limit, we have limnm(xn,xn)=0,

    limn,mmxnxm=0.

    Now, we prove that {xn} is M-Cauchy in X. For m,n in N with m>n and using the triangle inequality of an M-metric we get

    m(xn,xm)mxnxmm(xn,xn+1)mxnxn+1+m(xn+1,xm)mxn+1xmm(xn,xn+1)mxnxn+1+m(xn+1,xn+2)mxn+1xn+1+m(xn+2,xm)mxn+2xmm(xn,xn+1)mxnxn+1+m(xn+1,xn+2)mxn+1xn+2++m(xm1,xm)mxm1xmm(xn,xn+1)+m(xn+1,xn+2)++m(xm1,xm)=m1r=nm(xr,xr+1)m1r=n(r+1)ϕrM(m(x0,x1))m1rn0(r+1)ϕrM(m(x0,x1))m1rn0(r+1)ϕrM(m(x0,x1))<ϵ.

    m(xn,xm)mxnxm0, as n, we obtain limm,n(Mxnxmmxnxm)=0. Thus {xn} is a M-Cauchy sequence in X. Since (X,m) is M-complete, there exist xX such that

    limn(m(xn,x)mxnx)=0 andlimn(Mxnxmxnx)=0.

    Also, limnm(xn,xn)=0 gives that

    limnm(xn,x)=0 and limnMxnx=0, (2.3)
    limn{max(m(xn,x),m(x,x))}=0,

    which implies that m(x,x)=0 and hence we obtain mxT(x)=0. By using (2.1) and (2.3) with

    limnα(xn,x)1.

    Thus,

    limnHm(T(xn),T(x))limnϕM(m(xn,x))limnm(xn,x).
    limnHm(T(xn),T(x))=0. (2.4)

    Now from (2.3), (2.4), and xn+1T(xn), we have

    m(xn+1,T(x))Hm(T(xn),T(x))=0.

    Taking limit as n and using (2.4), we obtain that

    limnm(xn+1,T(x))=0. (2.5)

    Since mxn+1T(x)m(xn+1,T(x)) which gives

    limnmxn+1T(x)=0. (2.6)

    Using the condition (m4), we obtain

    m(x,T(x))supyT(x)mxym(x,T(x))mx,T(x)m(x,xn+1)mxxn+1+m(xn+1,T((x))mxn+1T(x).

    Applying limit as n and using (2.3) and (2.6), we have

    m(x,T(x))supyT(x)mxy. (2.7)

    From (m2), mxym(xy) for each yT(x) which implies that

    mxym(x,y)0.

    Hence,

    sup{mxym(x,y):yT(x)}0.

    Then

    supyT(x)mxyinfyT(x)m(x,y)0.

    Thus

    supyT(x)mxym(x,T(x)). (2.8)

    Now, from (2.7) and (2.8), we obtain

    m(T(x),x)=supyT(x)mxy.

    Consequently, owing to Lemma (1.12), we have x¯T(x)=T(x).

    Corollary 2.6. Let (X,m) be a complete M-metric space and anself mapping T:XX an α-admissible and (α,ϕM)-contraction mapping. Assume that thefollowing properties hold:

    (i) there exists x0X such that α(x0,T(x0))1,

    (ii) either T is continuous or for any sequence {xn}X with α(xn,xn+1)1 for all nN and {xn}x as n , we have α(xn,x)1 for all nN. Then T has a fixed point.

    Some fixed point results in ordered M-metric space.

    Definition 2.7. Let (X,) be a partially ordered set. A sequence {xn}X is said to be non-decreasing if xnxn+1 for all n.

    Definition 2.8. [16] Let F and G be two nonempty subsets of partially ordered set (X,). The relation between F and G is defined as follows: F1G if for every xF, there exists yG such that xy.

    Definition 2.9. Let (X,m,) be a partially ordered set on M-metric. A set-valued mapping T:XCBm(X) is said to be ordered (α,ϕM)-contraction if for all x,yX, with xy we have

    Hm(T(x),T(y))ϕM(m(x,y))

    where ϕMΨ. Suppose that α:X×X[0,) is defined by

    α(x,y)={1     if Tx1Ty0       otherwise.

    A mapping T is called α-admissible if

    α(x,y)1α(a1,b1)1,

    for each a1T(x) and b1T(y).

    Theorem 2.10. Let (X,m,) be a partially orderedcomplete M-metric space and T:XCBm(X) an α-admissible ordered (α,ϕM)-contraction mapping satisfying the following conditions:

    (i) there exist x0X such that {x0}1{T(x0)}, α(x0,a1)1 for each a1T(x0),

    (ii) for every x,yX, xy implies T(x)1T(y),

    (iii) If {xn}X is a non-decreasing sequence such that xnxn+1 for all n and {xn}xX as n gives xnx for all nN. Then T has a fixed point.

    Proof. By assumption (i) there exist x1T(x0) such that x0x1 and α(x0,x1)1. By hypothesis (ii), T(x0)1T(x1). Let us assume that there exist x2T(x1) such that x1x2 and we have the following

    m(x1,x2)Hm(T(x0),T(x1))+ϕM(m(x0,x1)).

    In the same way, there exist x3T(x2) such that x2x3 and

    m(x2,x3)Hm(T(x1),T(x2))+ϕ2M(m(x0,x1)).

    Following the similar arguments, we have a sequence {xn}X  and xn+1T(xn) for all n0 satisfying x0x1x2x3...xnxn+1. The proof is complete follows the arguments given in Theorem 2.5.

    Example 2.11. Let X=[16,1] be endowed with an M -metric given by m(x,y)=x+y2. Define T:XCBm(X) by

    T(x)={{12x+16,14}, if x=16{x2,x3},  if 14x13{23,56},  if 12x1.

    Define a mapping α:X×X[0,) by

    α(x,y)={1     if x,y[14,13]0       otherwise.

    Let ϕM:R+R+ be given by ϕM(t)=1710 where ϕMΨ, for x,yX. If x=16, y=14 then m(x,y)=524, and

    Hm(T(x),T(y))=Hm({312,14},{18,112})=max(m({312,14},{18,112}),m({18,112},{312,14}))=max{316,212}=316ϕM(t)m(x,y).

    If x=13, y=12 then m(x,y)=512, and

    Hm(T(x),T(y))=Hm({16,19},{23,1})=max(m({16,19},{23,1}),m({23,1},{16,19}))=max{1736,718}=1736ϕM(t)m(x,y).

    If x=16, y=1, then m(x,y)=712 and

    Hm(T(x),T(y))=Hm({312,14},{23,56})=max(m({312,14},{23,56}),m({23,56},{312,14}))=max{1124,1324}=1324ϕM(t)m(x,y).

    In all cases, T is (α,ϕM)-contraction mapping. If x0=13, then T(x0)={x2,x3}.Therefore α(x0,a1)1 for every a1T(x0). Let x,yX be such that α(x,y)1, then x,y[x2,x3] and T(x)={x2,x3} and T(y)= {x2,x3} which implies that α(a1,b1)1 for every a1T(x) and b1T(x). Hence T is α-admissble.

    Let {xn}X be a sequence such that α(xn,xn+1)1 for all n in N and xn converges to x as n converges to , then xn[x2,x3]. By definition of α -admissblity, therefore x[x2,x3] and hence α(xn,x)1. Thus all the conditions of Theorem 2.3 are satisfied. Moreover, T has a fixed point.

    Example 2.12. Let X={(0,0),(0,15),(18,0)} be the subset of R2 with order defined as: For (x1,y1),(x2,y2)X, (x1,y1)(x2,y2) if and only if x1x2, y1y2. Let m:X×XR+ be defined by

    m((x1,y1),(x2,y2))=|x1+x22|+|y1+y22|, for x=(x1,y1), y=(x2,y2)X.

    Then (X,m) is a complete M-metric space. Let T:XCBm(X) be defined by

    T(x)={{(0,0)}, if x=(0,0),{(0,0),(18,0)},  if x(0,15){(0,0)},  if x(18,0).

    Define a mapping α:X×X[0,) by

    α(x,y)={1     if x,yX0       otherwise.

    Let ϕM:R+R+ be given by ϕM(t)=12. Obviously, ϕMΨ. For x,yX,

    if x=(0,15) and y=(0,0), then Hm(T(x),T(y))=0 and m(x,y)=110 gives that

    Hm(T(x),T(y))=Hm({(0,0),(18,0)},{(0,0)})=max(m({(0,0),(18,0)},{(0,0)}),m({(0,0)},{(0,0),(18,0)}))=max{0,0}=0ϕM(t)m(x,y).

    If x=(18,0) and y=(0,0) then Hm(T(x),T(y))=0, and m(x,y)=116 implies that

    Hm(T(x),T(y))ϕM(t)m(x,y).

    If x=(0,0) and y=(0,0) then Hm(T(x),T(y))=0, and m(x,y)=0 gives

    Hm(T(x),T(y))ϕM(t)m(x,y).

    If x=(0,15) and y=(0,15) then Hm(T(x),T(y))=0, and m(x,y)=15 implies that

    Hm(T(x),T(y))ϕM(t)m(x,y).

    If x=(0,18) and y=(0,18) then Hm(T(x),T(y))=0, and m(x,y)=18 gives that

    Hm(T(x),T(y))ϕM(t)m(x,y).

    Thus all the condition of Theorem 2.10 satisfied. Moreover, (0,0) is the fixed point of T.

    In this section, we present an application of our result in homotopy theory. We use the fixed point theorem proved for set-valued (α,ϕM)-contraction mapping in the previous section, to establish the result in homotopy theory. For further study in this direction, we refer to [6,35].

    Theorem 3.1. Suppose that (X,m) is a complete M-metricspace and A and B are closed and open subsets of X respectively, suchthat AB. For a,bR, let T:B×[a,b]CBm(X) be aset-valued mapping satisfying the following conditions:

    (i) xT(y,t) for each yB/Aand t[a,b],

    (ii) there exist ϕMΨ and α:X×X[0,) such that

    α(x,y)Hm(T(x,t),T(y,t))ϕM(m(x,y)),

    for each pair (x,y)B×B and t[a,b],

    (iii) there exist a continuous function Ω:[a,b]R such that for each s,t[a,b] and xB, we get

    Hm(T(x,s),T(y,t))ϕM|Ω(s)Ω(t)|,

    (iv) if xT(x,t),then T(x,t)={x},

    (v) there exist x0 in X such that x0T(x0,t),

    (vi) a function :[0,)[0,) defined by (x)=xϕM(x) is strictly increasing and continuous if T(.,t) has a fixed point in B for some t[a,b], then T(.,t) has afixed point in A for all t[a,b]. Moreover, for a fixed t[a,b], fixed point is unique provided that ϕM(t)=12t where t>0.

    Proof. Define a mapping α:X×X[0,) by

    α(x,y)={1     if xT(x,t), yT(y,t) 0       otherwise.

    We show that T is α-admissible. Note that α(x,y)1 implies that xT(x,t) and yT(y,t) for all t[a,b]. By hypothesis (iv), T(x,t)={x} and T(y,t)={y}. It follows that T is α -admissible. By hypothesis (v), there exist x0X such that x0(x0,t) for all t, that is α(x0,x0)1. Suppose that α(xn,xn+1)1 for all n and xn converges to q as n approaches to and xnT(xn,t) and xn+1T(xn+1,t) for all n and t[a,b] which implies that qT(q,t) and thus α(xn,q)1. Set

    D={t[a,b]: xT(x,t) for xA}.

    So T(.,t) has a fixed point in B for some t[a,b], there exist xB such that xT(x,t). By hypothesis (i) xT(x,t) for t[a,b] and xA so Dϕ. Now we now prove that D is open and close in [a,b]. Let t0D and x0A with x0T(x0,t0). Since A is open subset of X, ¯Bm(x0,r)A for some r>0. For ϵ=r+mxx0ϕ(r+mxx0) and a continuous function Ω on [a,b], there exist δ>0 such that

    ϕM|Ω(t)Ω(t0)|<ϵ for all t(t0δ,t0+δ).

    If t(t0δ,t0+δ) for xBm(x0,r)={xX:m(x0,x)mx0x+r} and lT(x,t), we obtain

    m(l,x0)=m(T(x,t),x0)=Hm(T(x,t),T(x0,t0)).

    Using the condition (iii) of Proposition 1.13 and Proposition 1.18, we have

    m(l,x0)Hm(T(x,t),T(x0,t0))+Hm(T(x,t),T(x0,t0)) (2.9)

    as xT(x0,t0) and xBm(x0,r)AB, t0[a,b] with α(x0,x0)1. By hypothesis (ii), (iii) and (2.9)

    m(l,x0)ϕM|Ω(t)Ω(t0)|+α(x0,x0)Hm(T(x,t),T(x0,t0))ϕM|Ω(t)Ω(t0)|+ϕM(m(x,x0))ϕM(ϵ)+ϕM(mxx0+r)ϕM(r+mxx0ϕM(r+mxx0))+ϕM(mxx0+r)<r+mxx0ϕM(r+mxx0)+ϕM(mxx0+r)=r+mxx0.

    Hence l¯Bm(x0,r) and thus for each fixed t(t0δ,t0+δ), we obtain T(x,t)¯Bm(x0,r) therefore T:¯Bm(x0,r)CBm(¯Bm(x0,r)) satisfies all the assumption of Theorem (3.1) and T(.,t) has a fixed point ¯Bm(x0,r)=Bm(x0,r)B. But by assumption of (i) this fixed point belongs to A. So (t0δ,t0+δ)D, thus D is open in [a,b]. Next we prove that D is closed. Let a sequence {tn}D with tn converges to t0[a,b] as n approaches to . We will prove that t0 is in D.

    Using the definition of D, there exist {tn} in A such that xnT(xn,tn) for all n. Using Assumption (iii)(v), and the condition (iii) of Proposition 1.13, and an outcome of the Proposition 1.18, we have

    m(xn,xm)Hm(T(xn,tn),T(xm,tm))Hm(T(xn,tn),T(xn,tm))+Hm(T(xn,tm),T(xm,tm))ϕM|Ω(tn)Ω(tm)|+α(xn,xm)Hm(T(xn,tm),T(xm,tm))ϕM|Ω(tn)Ω(tm)|+ϕM(m(xn,xm))m(xn,xm)ϕM(m(xn,xm))ϕM|Ω(tn)Ω(tm)|(m(xn,xm))ϕM|Ω(tn)Ω(tm)|(m(xn,xm))<|Ω(tn)Ω(tm)|m(xn,xm)<1|Ω(tn)Ω(tm)|.

    So, continuity of 1, and convergence of {tn}, taking the limit as m,n in the last inequality, we obtain that

    limm,nm(xn,xm)=0.

    Sine mxnxmm(xn,xm), therefore

    limm,nmxnxm=0.

    Thus, we have limnm(xn,xn)=0=limmm(xm,xm). Also,

    limm,n(m(xn,xm)mxnxm)=0, limm,n(Mxnxmmxnxm).

    Hence {xn} is an M-Cauchy sequence. Using Definition 1.4, there exist x in X such that

    limn(m(xn,x)mxnx)=0 and limn(Mxnxmxnx)=0.

    As limnm(xn,xn)=0, therefore

    limnm(xn,x)=0 and limnMxnx=0.

    Thus, we have m(x,x)=0. We now show that xT(x,t). Note that

    m(xn,T(x,t))Hm(T(xn,tn),T(x,t))Hm(T(xn,tn),T(xn,t))+Hm(T(xn,t),T(x,t))ϕM|Ω(tn)Ω(t)|+α(xn,t)Hm(T(xn,t),T(x,t))ϕM|Ω(tn)Ω(t)|+ϕM(m(xn,t)).

    Applying the limit n in the above inequality, we have

    limnm(xn,T(x,t))=0.

    Hence

    limnm(xn,T(x,t))=0. (2.10)

    Since m(x,x)=0, we obtain

    supyT(x,t)mxy=supyT(x,t)min{m(x,x),m(y,y)}=0. (2.11)

    From above two inequalities, we get

    m(x,T(x,t))=supyT(x,t)mxy.

    Thus using Lemma 1.12 we get xT(x,t). Hence xA. Thus xD and D is closed in [a,b], D=[a,b] and D is open and close in [a,b]. Thus T(.,t) has a fixed point in A for all t[a,b]. For uniqueness, t[a,b] is arbitrary fixed point, then there exist xA such that xT(x,t). Assume that y is an other point of T(x,t), then by applying condition 4, we obtain

    m(x,y)=Hm(T(x,t),T(y,t))αM(x,y)Hm(T(x,t),T(y,t))ϕM(m(x,y)).

    ForϕM(t)=12t, where t>0, the uniqueness follows.

    In this section we will apply the previous theoretical results to show the existence of solution for some integral equation. For related results (see [13,20]). We see for non-negative solution of (3.1) in X=C([0,δ],R). Let X=C([0,δ],R) be a set of continuous real valued functions defined on [0,δ] which is endowed with a complete M-metric given by

    m(x,y)=supt[0,δ](|x(t)+x(t)2|) for all x,yX.

    Consider an integral equation

    v1(t)=ρ(t)+δ0h(t,s)J(s,v1(s))ds for all 0tδ. (3.1)

    Define g:XX by

    g(x)(t)=ρ(t)+δ0h(t,s)J(s,x(s))ds

    where

    (i) for δ>0,  (a) J:[0,δ]×RR, (b) h:[0,δ]×[0,δ][0,), (c) ρ:[0,δ]R are all continuous functions

    (ii) Assume that σ:X×XR is a function with the following properties,

    (iii) σ(x,y)0 implies that σ(T(x),T(y))0,

    (iv) there exist x0X such that σ(x0,T(x0))0,

    (v) if {xn}X is a sequence such that σ(xn,xn+1)0 for all nN and xnx as n, then σ(x,T(x))0

    (vi)

    supt[0,δ]δ0h(t,s)ds1

    where t[0,δ], sR,

    (vii) there exist ϕMΨ, σ(y,T(y))1 and σ(x,T(x))1 such that for each t[0,δ], we have

    |J(s,x(t))+J(s,y(t))|ϕM(|x+y|). (3.3)

    Theorem 4.1. Under the assumptions (i)(vii) theintegral Eq (3.1) has a solution in {X=C([0,δ],R) for all t[0,δ]}.

    Proof. Using the condition (vii), we obtain that

    m(g(x),g(y))=|g(x)(t)+g(y)(t)2|=|δ0h(t,s)[J(s,x(s))+J(s,y(s))2]ds|δ0h(t,s)|J(s,x(s))+J(s,y(s))2|dsδ0h(t,s)[ϕM|x(s)+y(s)2|]ds(supt[0,δ]δ0h(t,s)ds)(ϕM|x(s)+y(s)2|)ϕM(|x(s)+y(s)2|)
    m(g(x),g(y))ϕ(m(x,y))

    Define α:X×X[0,+) by

    α(x,y)={1     if σ(x,y)0 0       otherwise

    which implies that

    m(g(x),g(y))ϕM(m(x,y)).

    Hence all the assumption of the Corollary 2.6 are satisfied, the mapping g has a fixed point in X=C([0,δ],R) which is the solution of integral Eq (3.1).

    In this study we develop some set-valued fixed point results based on (α,ϕM)-contraction mappings in the context of M-metric space and ordered M-metric space. Also, we give examples and applications to the existence of solution of functional equations and homotopy theory.

    The authors declare that they have no competing interests.



    Conflict of interest



    All authors declare no conflict of interest

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