Study to Evaluate the Efficacy, Immunogenicity, and Safety of RSVpreF in Adults.

Efficacy Study

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits,vaccination plan, laboratory tests, lifestyle considerations, frequent symptomassessment by mobile device application, and other study procedures, includingcollection of nasal swabs by themselves and by study staff when indicated.

• Healthy participants who are determined by medical history, physical examination (ifrequired), and clinical judgment of the investigator to be eligible for inclusion inthe study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living orlong-term care residential facilities that provide minimal assistance, such that theparticipant is primarily responsible for self-care and activities of daily living.

• Capable of giving signed informed consent as described in the protocol, whichincludes compliance with the requirements and restrictions listed in the ICD and inthis protocol.

• Male or female participants ≥60 years of age.

• Male participants able to father children must agree to use a highly effectivemethod of contraception from the time of informed consent through at least 28days after study intervention administration.

• Female participants must not be of childbearing potential.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, inthe opinion of the investigator, contraindicate intramuscular injection.

• History of severe adverse reaction associated with a vaccine and/or severe allergicreaction (eg, anaphylaxis) to any component of the study intervention(s) or anyrelated vaccine.

• Serious chronic disorder including metastatic malignancy, end-stage renal diseasewith or without dialysis, clinically unstable cardiac disease, or any other disorderthat, in the investigator's opinion, excludes the participant from participating inthe study.

• Immunocompromised individuals with known or suspected immunodeficiency, asdetermined by history and/or laboratory/physical examination.

• Other medical or psychiatric condition including recent (within the past year) oractive suicidal ideation/behavior or laboratory abnormality that may increase therisk of study participation or, in the investigator's judgment, make the participantinappropriate for the study.

• Participation in other studies involving an investigational product within 28 daysprior to consent and/or through and including the 6-months follow-up visit (Visit 3).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study - Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from 60 days before study intervention administration or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before studyintervention administration.

• Previous vaccination with any licensed or investigational RSV vaccine or plannedreceipt during study participation.

• Investigator site staff or Pfizer employees directly involved in the conduct of thestudy, site staff otherwise supervised by the investigator, and their respectivefamily members.

Substudy A

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits,vaccination plan, laboratory tests, lifestyle considerations, frequent symptomassessment by mobile device application, and other study procedures, includingcollection of nasal swabs by themselves and by study staff when indicated.

• Healthy participants who are determined by medical history, physical examination (ifrequired), and clinical judgment of the investigator to be eligible for inclusion inthe study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living orlong-term care residential facilities that provide minimal assistance, such that theparticipant is primarily responsible for self-care and activities of daily living.

• Capable of giving signed informed consent as described in the protocol, whichincludes compliance with the requirements and restrictions listed in the ICD and inthis protocol.

• Male or female participants ≥60 years of age.

• Male participants able to father children must agree to use a highly effectivemethod of contraception from the time of informed consent through at least 28days after study intervention administration.

• Female participants must not be of childbearing potential.

• Participants who received RSVpreF in the efficacy study.

• Participants who have a Visit 2 serology sample available for testing from theefficacy study, completed the end-of-Season 2 visit (Visit 5), and did not meetexclusion criteria throughout the efficacy study duration.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, inthe opinion of the investigator, contraindicate intramuscular injection.

• History of severe adverse reaction associated with a vaccine and/or severe allergicreaction (eg, anaphylaxis) to any component of the study intervention(s) or anyrelated vaccine.

• Serious chronic disorder including metastatic malignancy, end-stage renal diseasewith or without dialysis, clinically unstable cardiac disease, or any other disorderthat, in the investigator's opinion, excludes the participant from participating inthe study.

• Immunocompromised individuals with known or suspected immunodeficiency, asdetermined by history and/or laboratory/physical examination.

• Other medical or psychiatric condition including recent (within the past year) oractive suicidal ideation/behavior or laboratory abnormality that may increase therisk of study participation or, in the investigator's judgment, make the participantinappropriate for the study.

• Participation in other studies involving an investigational product within 28 daysprior to consent and/or through and including the 6-months follow-up visit (Visit 103).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study

• Individuals who receive chronic systemic treatment with immunosuppressive therapy,including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, orradiotherapy, eg, for cancer or an autoimmune disease, from 60 days before studyintervention administration or planned receipt throughout the study. If systemiccorticosteroids have been administered short term (<14 days) for treatment of anacute illness, participants should not be enrolled in the study until corticosteroidtherapy has been discontinued for at least 28 days before study interventionadministration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin oreyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before studyintervention administration.

• Previous vaccination with any licensed or investigational RSV vaccine or plannedreceipt during study participation.

Note: This criterion does not include the receipt of RSVpreF in the efficacy study. Per inclusion criterion #6, receipt of RSVpreF in the efficacy study is required to participate in Substudy A.

• Investigator site staff or Pfizer employees directly involved in the conduct of thestudy, site staff otherwise supervised by the investigator, and their respectivefamily members.

• Participant was confirmed by the sponsor to have previously received the studyintervention more than once.

Substudy B

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits,vaccination plan, laboratory tests, lifestyle considerations, frequent symptomassessment by mobile device application, and other study procedures, includingcollection of nasal swabs by themselves and by study staff when indicated.

• Healthy participants who are determined by medical history, physical examination (ifrequired), and clinical judgment of the investigator to be eligible for inclusion inthe study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living orlong-term care residential facilities that provide minimal assistance, such that theparticipant is primarily responsible for self-care and activities of daily living.

• Capable of giving signed informed consent as described in the protocol, whichincludes compliance with the requirements and restrictions listed in the ICD and inthis protocol.

• Male or female participants ≥60 years of age.

• Male participants able to father children must agree to use a highly effectivemethod of contraception from the time of informed consent through at least 28days after study intervention administration.

• Female participants must not be of childbearing potential. 6. Participants whoreceived RSVpreF in the efficacy study.

• Participants who received RSVpreF in the efficacy study.

• Participants who have a Visit 2 serology sample available for testing from theefficacy study and did not meet exclusion criteria through Visit 4 of the efficacystudy.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, inthe opinion of the investigator, contraindicate intramuscular injection.

• History of severe adverse reaction associated with a vaccine and/or severe allergicreaction (eg, anaphylaxis) to any component of the study intervention(s) or anyrelated vaccine.

• Serious chronic disorder including metastatic malignancy, end-stage renal diseasewith or without dialysis, clinically unstable cardiac disease, or any other disorderthat, in the investigator's opinion, excludes the participant from participating inthe study.

• Immunocompromised individuals with known or suspected immunodeficiency, asdetermined by history and/or laboratory/physical examination.

• Other medical or psychiatric condition including recent (within the past year) oractive suicidal ideation/behavior or laboratory abnormality that may increase therisk of study participation or, in the investigator's judgment, make the participantinappropriate for the study.

• Participation in other studies involving an investigational product within 28 daysprior to consent and/or through and including the 6-months follow-up visit (Visit 203).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study - Individuals who receive chronic systemic treatment with immunosuppressive therapy, including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, or radiotherapy, eg, for cancer or an autoimmune disease, from 60 days before study intervention administration or planned receipt throughout the study. If systemic corticosteroids have been administered short term (<14 days) for treatment of an acute illness, participants should not be enrolled in the study until corticosteroid therapy has been discontinued for at least 28 days before study intervention administration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin or eyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before studyintervention administration.

• Previous vaccination with any licensed or investigational RSV vaccine or plannedreceipt during study participation.

Note: This criterion does not include the receipt of RSVpreF in the efficacy study. Per inclusion criterion #6, receipt of RSVpreF in the efficacy study is required to participate in Substudy B.

• Investigator site staff or Pfizer employees directly involved in the conduct of thestudy, site staff otherwise supervised by the investigator, and their respectivefamily members.

• Participant was confirmed by the sponsor to have previously received the studyintervention more than once.

• Participants who completed Vaccination 1 from the efficacy study less than 9 monthsor greater than 15 months prior to revaccination.

Substudy C

Inclusion Criteria:

• Participants who are willing and able to comply with all scheduled visits,vaccination plan, laboratory tests, lifestyle considerations, frequent symptomassessment by mobile device application, and other study procedures, when indicated.

• Healthy participants who are determined by medical history, physical examination (ifrequired), and clinical judgment of the investigator to be eligible for inclusion inthe study.

Note: Healthy participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, can be included. Specific criteria for participants with known stable infection with HIV, HCV, or HBV can be found in the protocol.

• Adults who are ambulatory and live in the community, or in assisted living orlong-term care residential facilities that provide minimal assistance, such that theparticipant is primarily responsible for self-care and activities of daily living.

• Capable of giving signed informed consent as described in the protocol, whichincludes compliance with the requirements and restrictions listed in the ICD and inthis protocol.

• Male or female participants ≥60 years of age.

• Participants who received RSVpreF in the efficacy study.

• Participants who have a Visit 2 serology sample available for testing from theefficacy study, completed the end-of-Season 2 visit (Visit 5), and did not meetexclusion criteria throughout the efficacy study duration.

Exclusion Criteria:

• Bleeding diathesis or condition associated with prolonged bleeding that would, inthe opinion of the investigator, contraindicate intramuscular injection.

• History of severe adverse reaction associated with a vaccine and/or severe allergicreaction (eg, anaphylaxis) to any component of the study intervention(s) or anyrelated vaccine.

• Serious chronic disorder including metastatic malignancy, end-stage renal diseasewith or without dialysis, clinically unstable cardiac disease, or any other disorderthat, in the investigator's opinion, excludes the participant from participating inthe study.

• Immunocompromised individuals with known or suspected immunodeficiency, asdetermined by history and/or laboratory/physical examination.

• Other medical or psychiatric condition including recent (within the past year) oractive suicidal ideation/behavior or laboratory abnormality that may increase therisk of study participation or, in the investigator's judgment, make the participantinappropriate for the study.

• Participation in other studies involving an investigational product within 28 daysprior to consent and/or through and including the 6-months follow-up visit (Visit 303 or Visit 306).

Note: This criterion does not apply to participants who are participating in a follow-up period for another study involving a study intervention that is an investigational drug or vaccine, if receipt of the last dose was at least 6 months prior to consenting for this study and there is no further dosing anticipated from the previous study during the participant's participation in this study

• Individuals who receive chronic systemic treatment with immunosuppressive therapy,including cytotoxic agents, monoclonal antibodies, systemic corticosteroids, orradiotherapy, eg, for cancer or an autoimmune disease, from 60 days before studyintervention administration or planned receipt throughout the study. If systemiccorticosteroids have been administered short term (<14 days) for treatment of anacute illness, participants should not be enrolled in the study until corticosteroidtherapy has been discontinued for at least 28 days before study interventionadministration. Inhaled/nebulized, intra articular, intrabursal, or topical (skin oreyes) corticosteroids are permitted.

Note: Participants with COPD or asthma can be enrolled if chronic corticosteroids do not exceed a dose equivalent to 10 mg/day of prednisone.

• Receipt of blood/plasma products or immunoglobulin within 60 days before studyintervention administration.

• Previous vaccination with any licensed or investigational RSV vaccine or plannedreceipt during study participation.

Note: This criterion does not include the receipt of RSVpreF in the efficacy study. Per inclusion criterion #6, receipt of RSVpreF in the efficacy study is required to participate in Substudy C.

• Investigator site staff or Pfizer employees directly involved in the conduct of thestudy, site staff otherwise supervised by the investigator, and their respectivefamily members.

• Participant was confirmed by the sponsor to have previously received the studyintervention more than once.

• Prior history of any subtype of Guillain-Barré syndrome of any etiology.

• Current or prior participation in Substudy A or Substudy B.

• Participants who completed Vaccination 1 from the efficacy study less than 32 monthsor greater than 40 months prior to revaccination.