• Frequency of significant increases in serum antibody to SARS-CoV S protein in ELISA and in neutralization tests, and increases in GMTs in sera collected 1 and 5 months after the booster dose of vaccine, versus sera collected before the 1st vaccination. [ Time Frame: Screening, 1 and 5 months after the booster dose of vaccine. ] [ Designated as safety issue: No ]
  
• Frequency and severity of solicited injection site and systemic signs and symptoms and unsolicited adverse events (AE) / serious adverse events (SAEs). [ Time Frame: 1 month after receipt of the first and second doses of vaccine. ] [ Designated as safety issue: Yes ]
  
• Frequency and description of serious adverse events (SAEs). [ Time Frame: 5 months after receipt of the booster dose of vaccine. ] [ Designated as safety issue: Yes ]
  

• Frequency of significant serum antibody increases and increases in GMTs, pre-vaccination compared to just before booster, as measured in neutralizing antibody tests and an ELISA against SARS-CoV S protein. [ Time Frame: Collected just before the first vaccination and at 1 month (just before booster). ] [ Designated as safety issue: No ]
  

Severe acute respiratory disease (SARS) is a recently emerged infectious disease that was first recognized in Guangdong Province, China, in November of 2002. This protocol concerns Phase 1 clinical testing of an inactivated, purified SARS Coronavirus (CoV) vaccine administered with and without aluminum hydroxide adjuvant. The rationale for development of vaccines against SARS-CoV is to provide a means of control in the event a new SARS-CoV epidemic occurs or there is a deliberate release of the virus. Inactivated SARS-CoV vaccine has been shown to induce neutralizing antibodies that block binding of the virus to its receptor, ACE2. The primary objectives of the study are to assess: reactogenicity of escalating doses of adjuvanted and non-adjuvanted, inactivated SARS-CoV vaccine among healthy young adult subjects given their first intramuscular (IM) vaccinations with this vaccine; reactogenicity of a repeat IM administration of the same material to healthy young adult subjects one month later; and development and persistence of immune responses to escalating doses of adjuvanted and non-adjuvanted, inactivated SARS-CoV vaccine 1 and 5 months after the second ("booster") vaccination. The secondary objective of this study is to assess immune responses to each vaccine 1 month after a single dose. This is a single center, Phase I, out-patient study of the reactogenicity (tolerability and safety) and immunogenicity of escalating doses of an inactivated SARS-CoV vaccine with and without aluminum hydroxide as an adjuvant. Each vaccine will be injected as primary and booster vaccinations a month apart in the subject's non-dominant deltoid muscle. Participants will include 72 healthy males or non-pregnant, non-lactating females, 18-40 years old from the Houston, TX area. The study will be conducted at Baylor College of Medicine in 2 sequential stages. This study consists of a preliminary dose-escalation stage (1.a, 1.b, and 1.c) followed by a dose comparison stage (2) as follows: Stage 1a (2.5 mcg), 7 subjects randomized in a 1:3:3 fashion to receive a 2 dose regimen of placebo, vaccine containing 2.5 mcg of antigen and no adjuvant, or 2.5 mcg of antigen and Alum adjuvant. Stage 1b (5.0 mcg), 7 subjects randomized in a 1:3:3 fashion to receive a 2 dose regimen of placebo, vaccine containing 5.0 mcg of antigen and no adjuvant, or 5.0 mcg of antigen and Alum adjuvant. Stage 1c (10.0 mcg), 4 subjects randomized in a 1:3 fashion to receive a 2 dose regimen of placebo or vaccine with 10 mcg of antigen and no adjuvant. Stage 2, 54 subjects (9 per vaccine group) randomized 1:1:1:1:1:1 to receive vaccines containing, 2.5, 5.0, or 10.0 mcg of antigen without adjuvant, or 2.5 or 5.0 mcg of antigen with Alum, or placebo. All subjects in both Stages 1 and 2 will receive 2 injections of the assigned study material at Day 0 and 1 month, and will be followed for reactogenicity and immunogenicity for approximately 6 months. The primary study endpoints include: frequency and severity of solicited injection site and systemic signs and symptoms and unsolicited adverse events (AEs)/serious adverse events (SAEs) for 1 month after receipt of the 1st and 2nd doses of vaccine; frequency and description of SAEs for 5 months after receipt of the booster dose of vaccine; and frequency of significant increases serum antibody to SARS-CoV S protein in enzyme-linked immunosorbent assay (ELISA) and in neutralization tests and increases in geometric mean titers (GMTs) in sera collected 1 and 5 months after the booster dose of each vaccine, versus those collected before the 1st vaccination. The secondary endpoint will be the frequency of significant serum antibody increases and increases in GMTs in sera collected at 1 month (just before booster) versus those collected just before the 1st vaccination, as measured in neutralizing antibody tests and an ELISA against SARS-CoV S protein.