I would be agreeable to say that the spirit of antichrist has revealed itself in Antiochus Epiphanes, Julius Caesar, Nero Caesar, the papacy at the time of the Reformation — and many others. There are many antichrist spirits that have gone out into the world.

However, nowhere does John Calvin write that the little horn of Daniel 7 is the pope or the papacy. In his Institutes of the Christian Religion, Calvin writes that the “Antichrist” spoken of by Paul (sic) may be compared to the person of Antiochus Epiphanes prophesied in Daniel 7:25. Calvin is not claiming here that the little horn is the same historical figure as the Man of Sin. In Calvin’s Institutes the little horn is Antiochus, but in his Commentary on Daniel, he is Julius Caesar.

Here are Calvin’s interpretations of the “little horn” of Daniel 7:

To some we seem slanderous and petulant, when we call the Roman Pontiff Antichrist. But those who think so perceive not that they are bringing a charge of intemperance against Paul, after whom we speak, nay, in whose very words we speak. But lest any one object that Paul’s words have a different meaning, and are wrested by us against the Roman Pontiff, I will briefly show that they can only be understood of the Papacy. Paul says that Antichrist would sit in the temple of God (2 Thess. 2:4). In another passage, the Spirit, portraying him in the person of Antiochus, says that his reign would be with great swelling words of vanity (Dan. 7:25). Hence we infer that his tyranny is more over souls than bodies, a tyranny set up in opposition to the spiritual kingdom of Christ. Then his nature is such, that he abolishes not the name either of Christ or the Church, but rather uses the name of Christ as a pretext, and lurks under the name of Church as under a mask. But though all the heresies and schisms which have existed from the beginning belong to the kingdom of Antichrist, yet when Paul foretells that defection will come, he by the description intimates that that seat of abomination will be erected, when a kind of universal defection comes upon the Church, though many members of the Church scattered up and down should continue in the true unity of the faith. But when he adds, that in his own time, the mystery of iniquity, which was afterwards to be openly manifested, had begun to work in secret, we thereby understand that this calamity was neither to be introduced by one man, nor to terminate in one man (see Calvin 2 Thess. 2:3; Dan. 7:9). Moreover, when the mark by which he distinguishes Antichrist is, that he would rob God of his honour and take it to himself, he gives the leading feature which we ought to follow in searching out Antichrist; especially when pride of this description proceeds to the open devastation of the Church. Seeing then it is certain that the Roman Pontiff has impudently transferred to himself the most peculiar properties of God and Christ, there cannot be a doubt that he is the leader and standard-bearer of an impious and abominable kingdom. (Calvin’s Institutes IV:7:25)

Now compare this statement with Calvin’s Commentary on Daniel:

Wherefore it is our duty not to read carelessly what is here written, but to weigh seriously and with the greatest diligence what the Spirit intends by this vision. I was attentive, therefore, says he, to the horns, and behold one small one arose among them. Here interpreters begin to vary; some twist this to mean the Pope, and others the Turk; but neither opinion seems to me probable; they are both wrong, since they think the whole course of Christ’s kingdom is here described, while God wished only to declare to his Prophet what should happen up to the first advent of Christ. This, then, is the error of all those who wish to embrace under this vision the perpetual state of the Church up to the end of the world. But the Holy Spirit’s intention was completely different. We explained at the beginning why this vision appeared to the Prophet because the minds of the pious would constantly fail them in the dreadful convulsions which were at hand, when they saw the supreme dominion pass over to the Persians. And then the Macedonians broke in upon them, and acquired authority throughout; the whole of the East, and afterwards those robbers who made war under Alexander suddenly became kings, partly by cruelty and partly by fraud and perfidy, which created more strife than outward hostility. And when the faithful saw all those monarchies perish, and the Roman Empire spring up like a new prodigy, they would lose their courage in such confused and turbulent changes. Thus this vision was presented to the Prophet, that all the children of God might understand what severe trials awaited them before the advent of Christ. Daniel, then, does not proceed beyond the promised redemption, and does not embrace, as I have said, the whole kingdom, of Christ, but is content to bring the faithful to that exhibition of grace which they hoped and longed for.

Daniel 2 and 7 deal with the same historical events. Daniel 2 comprises the interpretation of Nebuchadnezzar’s dream and Daniel 7 the vision during the reign of Belshazzar. Both Daniel 2 and 7 are meant to point the Jews to the coming of the Messiah — the King of kings.

Daniel 2:44 — And in the days of these kings shall the God of heaven set up a kingdom, which shall never be destroyed: and the kingdom shall not be left to other people, but it shall break in pieces and consume all these kingdoms, and it shall stand for ever.

And in the days of these kings — Simply put, in the days of the Roman Empire. At that time, the kingdom of God will be brought to earth by Jesus Christ shall never be destroyed but it shall war against the kingdoms of this world and they shall become part of the kingdom of God and of His Christ (Revelation 11:15).

The purpose of Daniel 2 and 7, as well as the entire prophecy of Daniel, is to point to the time of the Messiah. The purpose of Daniel is to identify Jesus Christ. If the fourth kingdom is the Roman Empire, then the Messiah appeared during that time and overcame the kingdoms of this world.

And conversely, if the Messiah appeared in the days of the fourth kingdom, then it does not follow that the fourth kingdom has continued beyond the time of the coming of Messiah’s kingdom to this day — either through the papacy or any other system of government.