As filed with the Securities and Exchange Commission on April 26, 2024

Registration Statement No. 333-   

UNITED STATES

SECURITIESAND EXCHANGE COMMISSION

Washington, D.C. 20549

FORM S-3

REGISTRATION STATEMENT

UNDER

THESECURITIES ACT OF 1933

Vaccinex, Inc.

(Exactname of registrant as specified in its charter)

Delaware

(State or other jurisdiction of incorporation or organization)

16-1603202

(I.R.S. Employer Identification Number)

1895 Mount Hope Avenue

Rochester, New York 14620

(585) 271-2700

(Address, including zip code, and telephone number, including area code, of registrant’s principal executive offices)

Maurice Zauderer, Ph.D.

President and Chief Executive Officer

Vaccinex, Inc.

1895 MountHope Avenue

Rochester, New York 14620

(585) 271-2700

(Name, address, including zip code, and telephone number, including area code, of agent for service)

Copies to:

Approximate date of commencement of proposed sale to public: From time to time after this registration statement is declared effective.

If the only securities being registered on this Form are being offered pursuant to dividend or interest reinvestment plans, please check the followingbox: ☐

If any of the securities being registered on this Form are to be offered on a delayed or continuous basis pursuant to Rule 415 under theSecurities Act of 1933, other than securities offered only in connection with dividend or interest reinvestment plans, check the following box: ☒

If this Form is filed to register additional securities for an offering pursuant to Rule 462(b) under the Securities Act, please check the following box andlist the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form isa post-effective amendment filed pursuant to Rule 462(c) under the Securities Act, check the following box and list the Securities Act registration statement number of the earlier effective registration statement for the same offering. ☐

If this Form is a registration statement pursuant to General Instruction I.D. or a post-effective amendment thereto that shall become effective upon filingwith the Commission pursuant to Rule 462(e) under the Securities Act, check the following box. ☐

If this Form is a post-effective amendment toa registration statement filed pursuant to General Instruction I.D. filed to register additional securities or additional classes of securities pursuant to Rule 413(b) under the Securities Act, check the following box. ☐

Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-acceleratedfiler, a smaller reporting company, or an emerging growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company,” and “emerging growth company” in Rule 12b-2 of the Exchange Act.

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition periodfor complying with any new or revised financial accounting standards provided pursuant to Section 7(a)(2)(B) of the Securities Act. ☐

The registrant hereby amends this registration statement on such date or dates as may be necessary to delay its effective date until the registrant shallfile a further amendment which specifically states that this registration statement shall thereafter become effective in accordance with Section 8(a) of the Securities Act of 1933 or until the registration statement shall become effective onsuch date as the Securities and Exchange Commission, acting pursuant to said Section 8(a), may determine.

The information in this prospectus is not complete and may be changed. The sellingsecurityholders may not sell these securities pursuant to this prospectus until the registration statement filed with the Securities and Exchange Commission is effective. This prospectus is not an offer to sell these securities and is not solicitingoffers to buy these securities in any jurisdiction where the offer or sale is not permitted.

SUBJECT TO COMPLETION, DATED APRIL 26, 2024

PRELIMINARY PROSPECTUS

Up to 193,000 Shares of Common Stock

Warrants to Purchase up to 193,000 Shares of Common Stock

This prospectus relates to the resale, from time to time, by the selling securityholders identified in this prospectus under the caption“Selling Securityholders,” or the Selling Securityholders, of (i) warrants, or the Warrants, to purchase up to 193,000 shares of our common stock, par value $0.0001 per share, or common stock, and (ii) 193,000 shares of our commonstock issuable to the Selling Securityholders upon the exercise of the Warrants, or the Shares (together with the Warrants, the Securities). The Warrants were issued to the Selling Securityholders in March 2024.

We are not selling any securities under this prospectus and will not receive any proceeds from the sale of Securities by the SellingSecurityholders hereunder. We will, however, receive the net proceeds of any Warrants exercised for cash. The Selling Securityholders will bear all commissions and discounts, if any, attributable to the sale of the Securities. We will bear allcosts, expenses, and fees in connection with the registration of the Securities.

The Selling Securityholders may sell the Securitiesoffered by this prospectus from time to time on terms to be determined at the time of sale through ordinary brokerage transactions or through any other means described in this prospectus under the caption “Plan of Distribution.” TheSecurities may be sold at fixed prices, at market prices prevailing at the time of sale, at prices related to prevailing market price or at negotiated prices.

Our common stock is listed on the Nasdaq Capital Market under the symbol “VCNX.” On April 25, 2024, the closing price of our commonstock was $5.93 per share.

We effected a 1-for-14 reversestock split of our outstanding shares of common stock on February 19, 2024, or the Reverse Stock Split. Prior to the Reverse Stock Split, we effected a 1-for-15reverse stock split of our outstanding shares of common stock on September 22, 2023, or the Prior Reverse Stock Split. Unless we specifically state otherwise, all information in this prospectus reflects the Reverse Stock Split and the PriorReverse Stock Split and no exercise of stock options or warrants.

Investing inour common stock involves a high degree of risk. See “Risk Factors” beginning on page 5 of this prospectus and under similar headings in the documents incorporated by reference into this prospectus.

Neither the Securities and Exchange Commission nor any state securities commission has approved or disapproved of these securities ordetermined if this prospectus is truthful or complete. Any representation to the contrary is a criminal offense.

The date ofthis prospectus is    , 2024.

TABLE OF CONTENTS

ABOUT THIS PROSPECTUS

This prospectus relates to the resale by the Selling Securityholders identified in this prospectus under the caption “SellingSecurityholders,” from time to time, of 193,000 shares of our common stock and warrants to purchase up to 193,000 shares of our common stock. We are not selling any securities under this prospectus, and we will not receive any proceeds from thesale of the Securities offered by the Selling Securityholders hereunder. We will, however, receive the net proceeds of any Warrants exercised for cash.

This prospectus is part of a registration statement on Form S-3 that we have filed with the Securitiesand Exchange Commission, or the SEC, using a shelf registration process. Under this registration statement, the Selling Securityholders may sell from time to time in one or more offerings the Securities described in this prospectus. It omits some ofthe information contained in the registration statement, and reference is made to the full registration statement for further information with regard to us and the securities being offered by the Selling Securityholders. Any statement contained inthe prospectus concerning the provisions of any document filed as an exhibit to the registration statement or otherwise with the SEC is not necessarily complete, and in each instance, reference is made to the document filed. You should review thecomplete document to evaluate such statements.

You should carefully read this prospectus, any documents that we incorporate by referencein this prospectus and the information below under the captions “Where You Can Find More Information” and “Incorporation of Documents By Reference” before making an investment decision. You should rely only on the informationcontained or incorporated by reference in this prospectus. We have not authorized any person to provide you with different information. If anyone provides you with additional, different, or inconsistent information, you should not rely on it. Thisprospectus is not an offer to sell these securities, and it is not soliciting an offer to buy these securities, in any jurisdiction where the offer or sale is not permitted.

You should not assume that the information in this prospectus or any documents we incorporate by reference herein is accurate as of any dateother than the date of each such document. Our business, financial condition, results of operations, and prospects may have changed since those dates.

This prospectus and the documents that are incorporated by reference herein contain certain market data and industry statistics and forecaststhat are based on studies and clinical trials sponsored by Vaccinex or third parties, independent industry publications and other publicly available information. Although we believe these sources are reliable, we do not guarantee the accuracy orcompleteness of this information and we have not verified any of this data. Further, many of these statements involve risks and uncertainties and are subject to change based on various factors, including those discussed or referenced under thecaption “Risk Factors” in this prospectus and under similar captions in the documents that are incorporated by reference herein. Accordingly, investors should not place undue reliance on this information.

References in this prospectus to the terms “Vaccinex,” “the Company,” “we,” “our,” and “us,”or other similar terms, mean Vaccinex, Inc. and our subsidiaries, unless we state otherwise or the context indicates otherwise.

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RISK FACTORS

Investing in our common stock involves a high degree of risk. You should carefully consider and evaluate all of the information containedin this prospectus and in the documents incorporated by reference in this prospectus before you decide to purchase our common stock. In particular, you should carefully consider and evaluate the risks and uncertainties described in “Part I– Item 1A. Risk Factors” of our most recent Annual Report on Form 10-K, as updated by the additional risks and uncertainties set forth or incorporated by reference herein. Additional risksand uncertainties that we are unaware of or that we believe are not material at this time could also materially adversely affect our business, financial condition, or results of operations. Any of these risks and uncertainties could materially andadversely affect our business, results of operations, and financial condition, which in turn could materially and adversely affect the trading price or value of our common stock. As a result, you could lose all or part of your investment.

This prospectus also contains forward-looking statements that involve risks and uncertainties. Our actual results could differ materiallyfrom those anticipated in these forward-looking statements as a result of certain factors, including the risks faced by us described below and elsewhere in this prospectus. See “Special Note Regarding Forward-Looking Statements” forinformation relating to these forward-looking statements.

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SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS

This prospectus contains forward-looking statements within the meaning of Section 27A of the Securities Act and Section 21E of theSecurities Exchange Act of 1934, as amended, or the Exchange Act, which statements involve substantial risks and uncertainties. All statements, other than statements of historical fact, included in this prospectus or the documents incorporatedherein by reference, including statements regarding our future results of operations and financial position, our business strategy and plans, and our objectives for future operations, are forward-looking statements. The words “may,”“will,” “should,” “expects,” “plans,” “anticipates,” “believes,” “estimates,” “predicts,” “potential,” “intends,” “continue,” andsimilar expressions that convey uncertainty of future events or outcomes are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words.

The forward-looking statements in this prospectus include, among other things, statements about:

These statements are only current predictions and are subject to known and unknown risks, uncertainties, and other factors that may causeour or our industry’s actual results, levels of activity, performance, or

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achievements to be materially different from those anticipated by the forward-looking statements. We discuss many of these risks in greater detail in the risk factors in our most recentAnnual Report on Form 10-K, our subsequent Quarterly Reports on Form 10-Q, and other filings we make with the SEC pursuant to Section 13(a), 13(c), 14, or15(d) of the Exchange Act. You should not rely upon forward-looking statements as predictions of future events.

Although we believe thatthe expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, or achievements. Except as required by law, after the date of this prospectus, we are under no duty toupdate or revise any of the forward-looking statements, whether as a result of new information, future events, or otherwise.

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USE OF PROCEEDS

The net proceeds from any disposition of the Securities will be received by the Selling Securityholders. We will not receive any of theproceeds from any such Securities offered by this prospectus. We will, however, receive the net proceeds of any Warrants exercised for cash. We have agreed to pay all costs, expenses, and fees relating to the registration of the Securities coveredby this prospectus.

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SELLING SECURITYHOLDERS

This prospectus covers 193,000 shares of our common stock and Warrants to purchase up to 193,000 shares of our common stock, all of which maybe sold or otherwise disposed of by the Selling Securityholders.

The following table sets forth certain information with respect to theSelling Securityholders, including (i) the shares of our common stock beneficially owned by the Selling Securityholders prior to this offering, including the Shares, (ii) the Warrants beneficially owned by the Selling Securityholders priorto this offering, (iii) the number of Shares being offered by the Selling Securityholders pursuant to this prospectus, (iv) the number of Warrants being offered by the Selling Securityholders pursuant to this prospectus, and (v) theSelling Securityholders’ beneficial ownership after completion of this offering, assuming that all of the Securities covered hereby (but none of the other securities, if any, held by the Selling Securityholders) are sold to third parties.

The table is based on information supplied to us by the Selling Securityholders, with beneficial ownership and percentage ownership determinedin accordance with the rules and regulations of the SEC and includes voting or investment power with respect to shares of stock. This information does not necessarily indicate beneficial ownership for any other purpose. The percentage of beneficialownership after this offering is based on 1,584,300 shares outstanding on April 25, 2024. In addition, the beneficial ownership amounts do not take into account certain limitations, including that a holder of warrants may beprohibited from exercising their warrants for shares of common stock to the extent that, as a result of such exercise, such holder, together with its affiliates, would beneficially own more than 4.99%, or the Beneficial Ownership Limitation, of thetotal number of shares of common stock issued and outstanding immediately after giving effect to such exercise.

The registration of theSecurities does not mean that the Selling Securityholders will sell or otherwise dispose of all or any of these Securities. The Selling Securityholders may sell or otherwise dispose of all, a portion or none of such Securities from time to time. Wedo not know the number of Securities, if any, that will be offered for sale or other disposition by the Selling Securityholders under this prospectus. Additionally, we do not know how long the Selling Securityholders will hold the Warrants, whetherany will exercise the Warrants, and upon exercise of the Warrants, how long such Selling Securityholders will hold the Shares before selling them, and we currently have no agreements, arrangements or understandings with the Selling Securityholdersregarding the sale of any of the Securities. Furthermore, the Selling Securityholders may have sold, transferred, or disposed of the Securities in transactions exempt from the registration requirements of the Securities Act since the date on whichwe filed this prospectus.

When we refer to the Selling Securityholders in this prospectus, we are referring to the SellingSecurityholders identified in this prospectus and, as applicable, their permitted transferees or other successors-in-interest that may be identified in asupplement to this prospectus or, if required, a post-effective amendment to the registration statement of which this prospectus is a part.

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Relationships with the Selling Securityholders

The Selling Securityholders have not within the past three years had any position, office or other material relationship with us or any of oursubsidiaries other than as holders of our securities. To our knowledge, the Selling Securityholders are not affiliates of any broker-dealer registered in the United States.

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DESCRIPTION OF WARRANTS

The following summary of certain terms and provisions of the Warrants that are being offered hereby is not complete and is subject to, andqualified in its entirety by, the provisions of the Warrants, the form of which is filed as an exhibit to the registration statement of which this prospectus forms a part. Prospective investors should carefully review the terms and provisions of theform of Warrant for a complete description of the terms and conditions of the Warrants.

Duration and Exercise Price

Each Warrant offered hereby has an initial exercise price per share equal to $7.64 per share. The Warrants became exercisable immediatelyupon issuance and will expire five years from the date of issuance. The exercise price and number of shares of common stock issuable upon exercise is subject to appropriate adjustment in the event of stock dividends, stock splits, reorganizations orsimilar events affecting our common stock and the exercise price.

Exercisability

The Warrants are exercisable, at the option of each holder, in whole or in part, by delivering a duly executed exercise notice accompanied bypayment in full for the number of shares of our common stock purchased upon such exercise (except in the case of a cashless exercise as discussed below). Except as agreed with individual holders of Warrants, a holder (together with its affiliates)may not exercise any portion of the Warrant to the extent that the holder would own more than 4.99% of the outstanding common stock immediately after exercise, except that upon at least 61 days’ prior notice from the holder to us, theholder may increase the Beneficial Ownership Limitation to a percentage not to exceed 9.99%. No fractional shares of common stock will be issued in connection with the exercise of a Warrant. In lieu of fractional shares, we will pay the holderan amount in cash equal to the fractional amount multiplied by the exercise price.

Cashless Exercise

If, at the time a holder exercises its Warrants, a registration statement registering the issuance of the shares of common stock underlying theWarrants under the Securities Act is not then effective or available, then in lieu of making the cash payment otherwise contemplated to be made to us upon such exercise in payment of the aggregate exercise price, the holder may elect instead toreceive upon such exercise (either in whole or in part) the net number of shares of common stock determined according to a formula set forth in the Warrants.

Fundamental Transaction

In theevent of a fundamental transaction, as described in the Warrants and generally including any reorganization, recapitalization or reclassification of our common stock, the sale, transfer or other disposition of all or substantially all of ourproperties or assets, our consolidation or merger with or into another person, the acquisition of more than 50% of our outstanding common stock, or any person or group becoming the beneficial owner of more than 50% of the voting power represented byour outstanding common stock, the holders of the Warrants will be entitled to receive upon exercise of the Warrants the kind and amount of securities, cash or other property that the holders would have received had they exercised the Warrantsimmediately prior to such fundamental transaction.

Transferability

Subject to applicable laws, a Warrant may be transferred at the option of the holder upon surrender of the Warrant together with theappropriate instruments of transfer and funds sufficient to pay any transfer taxes payable upon such transfer.

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Exchange Listing

We do not intend to list the Warrants on any securities exchange or nationally recognized trading system.

Rights as a Stockholder

Except asotherwise provided in the Warrants or by virtue of such holder’s ownership of shares of our common stock, the holders of the Warrants do not have the rights or privileges of holders of our common stock, including any voting rights, until theyexercise their Warrants.

Call Option

We have the option to “call” the exercise of any or all of a holder’s Warrants, from time to time, by giving a call notice tothe holder within 30 days after the public announcement by the Company of an increase, in pepinemab-treated patients relative to placebo-treated patients, with statistical significance having a p-value of lessthan or equal to 0.05, in the change of the FDG-PET standard uptake value ratio for brain metabolism between baseline and month 12 as assessed by [18F]fluorodeoxyglucose(FDG)-PET in the resting state following administration of 40 mg/kg pepinemab or placebo, as applicable, as described in the protocol for our SIGNAL-AD study and theassociated Statistical Analysis Plan; provided, that at the time of the notice the holder of the Warrant is not in possession of any material non-public information that was provided by us or any ofour officers, directors, employees, agents, or affiliates and there is an effective resale registration statement. During the call period, the holder may exercise the Warrant and purchase the called shares of common stock underlying the Warrant. Ifthe holder fails to timely exercise the Warrant for a number of shares of common stock equal to the number of called shares during the call period, our sole remedy will be to cancel an amount of called shares of common stock underlying the Warrantequal to such shortfall, with the Warrant no longer being exercisable with respect to such shares; provided, further, however, that to the extent that the issuance of Shares subject to a call notice would cause the holder to hold in excess of theBeneficial Ownership Limitation, upon exercise of such portion as set forth in the Warrant, and the terms of such portion of the warrant will be modified to (i) provide that the warrant shall be exercisable until exercised in full rather thanon or prior to the termination date as defined therein, (ii) provide for an exercise price of $0.0001 per Share, subject to adjustment thereunder, and (iii) permit the warrant to be exercised at any time by means of a “cashlessexercise”. The call period is a period of 20 trading days following the date on which the holder receives the call notice.

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PLAN OF DISTRIBUTION

We are registering the resale of the Securities on behalf of the Selling Securityholders. The Selling Securityholders and any of theirpledgees, assignees, and successors-in-interest may, from time to time, on a continuous or delayed basis, sell any or all of their Securities covered hereby directly toone or more purchasers or through brokers, dealers, or underwriters who may act solely as agents at market prices prevailing at the time of sale, at prices related to the prevailing market prices, at negotiated prices, or at fixed prices, which maybe changed on any stock exchange, market, or trading facility on which the Securities are traded or in private transactions. The sale of the Selling Securityholders’ Securities offered by this prospectus may be effected in one or more of thefollowing methods:

In order to comply with the securities laws of certain states, if applicable, the Securities of the Selling Securityholders may be sold onlythrough registered or licensed brokers or dealers. In addition, in certain states, such Securities may not be sold unless they have been registered or qualified for sale in the state or an exemption from the registration or qualification requirementis available and complied with.

The Selling Securityholders may also sell or transfer Securities pursuant to any available exemption fromthe registration requirements of the Securities Act, including under Rule 144 promulgated under the Securities Act, or Rule 144, if available, rather than under this prospectus. In addition, the Selling Securityholders may transfer the Securities byother means not described in this prospectus.

The Selling Securityholders may also sell the Securities directly to market makers actingas principals and/or broker-dealers acting as agents for themselves or their customers. Such broker-dealers may receive compensation in the form of discounts, concessions, or commissions from the Selling Securityholders and/or the purchasers ofSecurities for whom such broker-dealers may act as agents or to whom they sell as principal or both, which compensation as to a particular broker-dealer might be in excess of customary commissions. Market makers and block purchasers purchasing theSecurities will do so for their own account and at their own risk. It is possible that the Selling Securityholders will attempt to sell Securities in block transactions to market makers or other purchasers at a price that may be below the thenmarket price.

Brokers, dealers, underwriters, or agents participating in the distribution of the Securities held by the SellingSecurityholders as agents may receive compensation in the form of commissions, discounts, or concessions from the Selling Securityholders and/or purchasers of the Securities for whom the broker-dealers may act as agent.

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The Selling Securityholders may agree to indemnify any agent, dealer, or broker-dealer that participates in transactions involving sales of the Securities if liabilities are imposed on thatperson under the Securities Act.

The Selling Securityholders have advised us that they have not entered into any agreements,understandings, or arrangements with any underwriters or broker-dealers regarding the sale of their Securities, nor is there an underwriter or coordinating broker acting in connection with a proposed sale of Securities by the SellingSecurityholders. If we are notified by the Selling Securityholders that any material arrangement has been entered into with a broker-dealer for the sale of Securities, if required, we will file a supplement to this prospectus.

In connection with the sale of the Securities or interests therein, the Selling Securityholders may enter into hedging transactions withbroker-dealers or other financial institutions, which may in turn engage in short sales of the Securities in the course of hedging the positions they assume. The Selling Securityholders may also sell Securities short and deliver these Securities toclose out their short positions, or loan or pledge the Securities to broker-dealers that in turn may sell these Securities. The Selling Securityholders may also enter into option or other transactions with broker-dealers or other financialinstitutions or create one or more derivative securities that require the delivery to such broker-dealer or other financial institution of Securities offered by this prospectus, which securities such broker-dealer or other financial institution mayresell pursuant to this prospectus (as supplemented or amended to reflect such transaction).

With regard only to the Securities it sellsfor its own behalf, each Selling Securityholder may be deemed an “underwriter” within the meaning of the Securities Act. This offering as it relates to each Selling Securityholder will terminate on the date that all Securities offered bythe Selling Securityholder pursuant to this prospectus have been sold.

We may suspend the sale of Securities by the SellingSecurityholders pursuant to this prospectus for certain periods of time for certain reasons, including if the prospectus is required to be supplemented or amended to include additional material information.

If the Selling Securityholders use this prospectus for any sale of the Securities, the Selling Securityholders will be subject to theprospectus delivery requirements of the Securities Act.

We are required to pay the expenses in connection with the registration of theSecurities being registered hereunder. We have agreed to indemnify the Selling Securityholders against certain losses, claims, damages, and liabilities, including liabilities under the Securities Act.

We agreed to keep this prospectus effective until the date that (i) the Securities may be resold by the Selling Securityholders withoutregistration and without regard to any volume or manner-of-sale limitations by reason of Rule 144, without the requirement for us to be in compliance with the currentpublic information under Rule 144 or any other rule of similar effect or (ii) all of the Securities have been sold pursuant to this prospectus or Rule 144 or any other rule of similar effect.

Regulation M

Theanti-manipulation rules of Regulation M under the Exchange Act may apply to sales of the Securities and activities of the Selling Securityholders.

We have advised the Selling Securityholders that while they are engaged in a distribution of the Securities included in this prospectus theyare required to comply with Regulation M promulgated under the Exchange Act. With certain exceptions, Regulation M precludes the Selling Securityholders, any affiliated purchasers, and any broker-dealer or other person who participates in thedistribution from bidding for or purchasing, or attempting to induce any person to bid for or purchase any security that is the subject of the distribution until the entire distribution is complete. Regulation M also prohibits any bids or purchasesmade in order to stabilize the price of a security in connection with the distribution of that security. All of the foregoing may affect the marketability of the Securities offered hereby this prospectus.

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LEGAL MATTERS

The validity of the Securities offered hereby is being passed upon for us by Hogan Lovells US LLP, Baltimore, Maryland.

EXPERTS

The financial statements of Vaccinex, Inc. as of December 31, 2023, and 2022 and for each of the two years in the period endedDecember 31, 2023, incorporated by reference in this prospectus, have been audited by Deloitte & Touche LLP, an independent registered public accounting firm, as stated in their report. Such financial statements are incorporated byreference in reliance upon the report of such firm given their authority as experts in accounting and auditing.

INCORPORATION BY REFERENCE

The SEC allows us to “incorporate by reference” information into this prospectus, which means that we can disclose importantinformation to you by referring you to another document filed separately with the SEC. The SEC file number for each of the documents incorporated by reference in this prospectus is 001-38624. The documentsincorporated by reference into this prospectus contain important information that you should read about us.

The following documents are incorporated byreference into this document:

All reports and other documents we subsequently file pursuant to Section 13(a), 13(c), 14, or 15(d) of the Exchange Act prior to thetermination of this offering, including those filed after the date of the initial registration statement of which this prospectus is part and prior to the effectiveness of the registration statement, will also be incorporated by reference into thisprospectus and deemed to be part of this prospectus from the date of the filing of such reports and documents. We are not, however, incorporating by reference any documents or portions thereof, whether specifically listed above or filed in thefuture, that are not deemed “filed” with the SEC, including any information furnished pursuant to Items 2.02 or 7.01 of Form 8-K or related exhibits furnished pursuant to Item 9.01 of Form 8-K.

Any statement contained herein or in a document incorporated or deemed to beincorporated by reference into this document will be deemed to be modified or superseded for purposes of the document to the extent that a statement contained in this document or any other subsequently filed document that is deemed to beincorporated by reference into this document modifies or supersedes the statement.

You may request, orally or in writing, a copy of anyor all of the documents incorporated herein by reference. These documents will be provided to you at no cost, by contacting: Vaccinex, Inc., Attn: Corporate Secretary, 1895 Mount Hope Avenue, Rochester, New York 14620. In addition, copies of any orall of the documents incorporated herein by reference may be accessed at our website at www.vaccinex.com.

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WHERE YOU CAN FIND MORE INFORMATION

We are a reporting company and file annual, quarterly, and current reports, proxy and information statements, and other information with theSEC. This prospectus is part of a registration statement that we have filed with the SEC relating to the Securities to be offered under this prospectus. This prospectus does not contain all of the information set forth in the registration statementand the exhibits to the registration statement. For further information with respect to us and the Securities to be offered under this prospectus, we refer you to the registration statement and the exhibits and schedules filed as a part of theregistration statement.

The SEC maintains an internet site that contains reports, proxy and information statements, and other informationregarding issuers that file electronically with the SEC, where you may read and copy the registration statement, as well as our reports, proxy and information statements, and other information. The address of the SEC’s web site iswww.sec.gov.

Copies of certain information filed by us with the SEC are also available on our website at www.vaccinex.com.

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PART II

INFORMATION NOT REQUIRED IN PROSPECTUS

Item 14. Other Expenses of Issuance and Distribution.

The following table sets forth the expenses to be incurred in connection with the offering described in this registration statement, all ofwhich will be paid by the Registrant. All amounts are estimates except the SEC registration fee.

Item 15. Indemnification of Directors and Officers.

Section 102(b)(7) of the Delaware General Corporation Law, or the DGCL, provides, in general, that a Delaware corporation, in itscertificate of incorporation, may limit the personal liability of a director or officer to the corporation or its stockholders for monetary damages for breach of fiduciary duties as a director or officer, except for liability for any:

Section 145(a) of the DGCL provides, in general, that a Delaware corporation may indemnify any person who was oris a party, or is threatened to be made a party, to any threatened, pending, or completed action, suit, or proceeding, whether civil, criminal, administrative, or investigative (other than an action by or in the right of the corporation) becausethat person is or was a director, officer, employee, or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee, or agent of another corporation or other enterprise. The indemnity may includeexpenses (including attorneys’ fees), judgments, fines, and amounts paid in settlement actually and reasonably incurred by the person in connection with such action, so long as the person acted in good faith and in a manner he or she reasonablybelieved was in or not opposed to the corporation’s best interests, and, with respect to any criminal action or proceeding, had no reasonable cause to believe his or her conduct was unlawful.

Section 145(b) of the DGCL provides, in general, that a Delaware corporation may indemnify any person who was or is a party, or isthreatened to be made a party, to any threatened, pending, or completed action or suit by or in the right of the corporation to obtain a judgment in its favor because the person is or was a director, officer, employee, or agent of the corporation,or is or was serving at the request of the corporation as a director, officer, employee, or agent of another corporation or other enterprise. The indemnity may include expenses (including attorneys’ fees) actually and reasonably incurred by theperson in connection with the defense or settlement of such action, so long as the person acted in good faith and in a manner the person reasonably believed was in or not opposed to the corporation’s best interests, except that noindemnification shall be permitted without judicial approval if a court has determined that the person is to be liable to the corporation with respect to such claim. Section 145(c) of the DGCL provides that, if a present or former director orofficer has been successful in defense of any action referred to in Sections 145(a) and (b) of the DGCL, the corporation must

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indemnify such officer or director against the expenses (including attorneys’ fees) he or she actually and reasonably incurred in connection with such action.

Section 145(g) of the DGCL provides, in general, that a corporation may purchase and maintain insurance on behalf of any person who is orwas a director, officer, employee, or agent of the corporation, or is or was serving at the request of the corporation as a director, officer, employee, or agent of another corporation or other enterprise against any liability asserted against andincurred by such person, in any such capacity, or arising out of his or her status as such, whether or not the corporation could indemnify the person against such liability under Section 145 of the DGCL.

Our amended and restated certificate of incorporation, or Charter, and our amended and restated bylaws provide for the indemnification of ourdirectors and officers to the fullest extent permitted under the DGCL.

We have entered into separate indemnification agreements with allof our directors and officers in addition to the indemnification provided for in our Charter and our amended and restated bylaws. These indemnification agreements provide, among other things, that we will indemnify our directors and officers forcertain expenses, including damages, judgments, fines, penalties, settlements and costs, and attorneys’ fees and disbursements, incurred by a director or officer in any claim, action, or proceeding arising in his or her capacity as a directoror officer of our company, or in connection with service at our request for another corporation or entity. The indemnification agreements also provide for procedures that will apply in the event that a director or officer makes a claim forindemnification.

We also maintain a directors’ and officers’ insurance policy pursuant to which our directors and officers areinsured against liability for actions taken in their capacities as directors and officers.

Item 16. Exhibits.

EXHIBIT INDEX

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Item 17. Undertakings.

(a) The undersigned registrant hereby undertakes:

(1) To file, during any period in which offers or sales are being made, apost-effective amendment to this registration statement:

(i) To include anyprospectus required by Section 10(a)(3) of the Securities Act;

(ii) To reflect in the prospectus any facts or eventsarising after the effective date of the registration statement (or the most recent post-effective amendment thereof) which, individually or in the aggregate, represent a fundamental change in the informationset forth in the registration statement. Notwithstanding the foregoing, any increase or decrease in volume of securities offered (if the total dollar value of securities offered would not exceed that which was registered) and any deviation from thelow or high end of the estimated maximum offering range may be reflected in the form of prospectus filed with the SEC pursuant to Rule 424(b) if, in the aggregate, the changes in volume and price represent no more than 20% change in the maximumaggregate offering price set forth in the “Calculation of Registration Fee” table in the effective registration statement;

(iii) To include any material information with respect to the plan of distribution not previously disclosed in the registrationstatement or any material change to such information in the registration statement;

provided, however, thatparagraphs (a)(1)(i), (a)(1)(ii), and (a)(1)(iii) do not apply if the information required to be included in a post-effective amendment by those paragraphs is contained in reports filed with or furnished to the SEC by the registrant pursuant toSection 13 or Section 15(d) of the Exchange Act that are incorporated by reference in the registration statement, or is contained in a form of prospectus filed pursuant to Rule 424(b) that is part of the registration statement.

(2) That, for the purpose of determining any liability under the Securities Act, each suchpost-effective amendment shall be deemed to be a new registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bonafide offering thereof.

(3) To remove from registration by means of apost-effective amendment any of the securities being registered which remain unsold at the termination of the offering.

(5) That, for the purpose of determining liability under the Securities Act to any purchaser:

(i) Each prospectus filed by the registrant pursuant to Rule 424(b)(3) shall be deemed to be part of the registration statementas of the date the filed prospectus was deemed part of and included in the registration statement; and

(ii) Eachprospectus required to be filed pursuant to Rule 424(b)(2), (b)(5), or (b)(7) as part of a registration statement in reliance on Rule 430B relating to an offering made pursuant to Rule 415(a)(1)(i), (vii), or (x) for the purpose ofproviding the information required by Section 10(a) of the Securities Act shall be deemed to be part of and included in the registration statement as of the earlier of the date such form of prospectus is first used after effectiveness or thedate of the first contract of sale of securities in the offering described in the prospectus. As provided in Rule 430B, for liability purposes of the issuer and any person that is at that date an underwriter, such date shall be deemed to be a neweffective date of the registration statement relating to the securities in the registration statement to which the prospectus relates, and the offering of such securities at that time shall be deemed to be the initial bona fide offeringthereof. Provided, however, that no statement made in a registration statement or prospectus that is part of the registration statement or made in a document incorporated or deemed incorporated by reference into the registration statementor prospectus that is part of the registration statement will, as to a purchaser with a time of contract of sale prior to such effective date, supersede or modify any statement that was made in the registration statement or prospectus that was partof the registration statement or made in any such document immediately prior to such effective date.

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(b) The undersigned registrant hereby undertakes that, for purposes of determining anyliability under the Securities Act, each filing of the registrant’s annual report pursuant to Section 13(a) or Section 15(d) of the Exchange Act that is incorporated by reference in this registration statement shall be deemed to be anew registration statement relating to the securities offered therein, and the offering of such securities at that time shall be deemed to be the initial bona fide offering thereof.

(h) Insofar as indemnification for liabilities arising under the Securities Act may be permitted to directors, officers, and controllingpersons of the registrant pursuant to the foregoing provisions, or otherwise, the registrant has been advised that in the opinion of the SEC such indemnification is against public policy as expressed in the Securities Act and is, therefore,unenforceable. In the event that a claim for indemnification against such liabilities (other than the payment by the registrant of expenses incurred or paid by a director, officer, or controlling person of the registrant in the successful defense ofany action, suit or proceeding) is asserted by such director, officer, or controlling person in connection with the securities being registered, the registrant will, unless in the opinion of its counsel the matter has been settled by controllingprecedent, submit to a court of appropriate jurisdiction the question whether such indemnification by it is against public policy as expressed in the Securities Act and will be governed by the final adjudication of such issue.

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SIGNATURES

Pursuant to the requirements of the Securities Act of 1933, as amended, the registrant certifies that it has reasonable grounds to believethat it meets all of the requirements for filing on Form S-3 and has duly caused this registration statement to be signed on its behalf by the undersigned, thereunto duly authorized, in the City of Rochester,in the State of New York, on April 26, 2024.

Pursuant to the requirements of the Securities Act of 1933, as amended, this registration statement hasbeen signed by the following persons in the capacities and on the dates indicated.