The purpose of this study is to assess the safety and reactogenicity of Ad26.COV2.S (0.3 milliliter [mL] versus 0.5 mL) and to demonstrate non-inferiority (NI) of Ad26.COV2.S (0.3 mL versus 0.5 mL), 28 days after vaccination.

Inclusion Criteria:

• Participant must sign an informed consent form (ICF) indicating that he or she understands the purpose, procedures and potential risks and benefits of the study, and is willing to participate in the study
• Participant must be healthy, in the investigator's clinical judgment, as confirmed by medical history, physical examination, and vital signs performed at screening. Participant may have underlying illnesses, as long as the symptoms and signs are medically controlled and not considered to be comorbidities related to an increased risk of severe coronavirus disease-2019 (COVID-19), except for smoking, which is allowed. If on medication for a condition, the medication dose must have been stable for at least 12 weeks preceding vaccination and expected to remain stable for the duration of the study
• All participants of childbearing potential must: a) have a negative highly sensitive urine pregnancy test at screening; b) have a negative highly sensitive urine pregnancy test immediately on the day of and prior to study vaccine administration
• Participant agrees to not donate bone marrow, blood, and blood products from the first study vaccine administration until 3 months after receiving the study vaccine
• Participant must be willing to provide verifiable identification, has means to be contacted and to contact the investigator during the study

Exclusion Criteria:

• Participant has a history of malignancy within 5 years before screening (exceptions are squamous and basal cell carcinomas of the skin and carcinoma in situ of the cervix, or malignancy, which is considered cured with minimal risk of recurrence)
• Participant has a known or suspected allergy or history of anaphylaxis or other serious adverse reactions to vaccines or their excipients (including specifically the excipients of the study vaccine)
• Participant has a history of any neurological disorders or seizures including Guillain-barre syndrome, with the exception of febrile seizures during childhood
• Participant has a history of chronic urticaria (recurrent hives), eczema or adult atopic dermatitis
• Participant received treatment with immunoglobulins in the 3 months or exogenous blood products (autologous blood transfusions are not exclusionary) in the 4 months before the planned administration of the study vaccine or has any plans to receive such treatment during the study
• Upper limit of body mass index (BMI) range should not be considered in participants with comorbidities that are or might be associated with an increased risk of progression to severe COVID-19. Participants may have hypertension of mild severity, as long as it is stable and medically controlled as defined by no change in medication over the past 6 months (except for issues of tolerability or use of similar drug with same mechanism of action, example, thiazides, beta blockers, alpha blockers at the same effective dose)
• Participant who is an employee of the sponsor, investigator or study site with direct involvement in the proposed study or other studies under the direction of that investigator or study site, including the family members of those employees or the investigator

The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu