Two New Tuberculosis Vaccines Prove Safe But Fail to Provide Broad Protection in India Trial

The PreVenTB clinical trial tested two tuberculosis vaccines, VPM1002 and Immuvac, across 18 sites in six Indian states, enrolling 12,717 household contacts of TB patients aged 6 years and older between July 2019 and December 2020. While both vaccines proved safe and induced immune responses, they failed to provide general protection against tuberculosis or prevent latent infection, though they did prevent progression to active TB in those with latent infection. VPM1002 showed notable effectiveness against extrapulmonary tuberculosis, achieving 50.4% protection overall and 79.5% in adults aged 36-60 years, and provided protection in children aged 6 to under 14 years. However, neither vaccine protected underweight individuals or showed effectiveness against pulmonary tuberculosis, limiting their potential as broad TB prevention tools despite completing 38 months of follow-up with 96.7% participant retention.

Trial Design and Participant Demographics

• ▪The PreVenTB trial was conducted across 18 sites in six Indian states between July 2019 and December 2020.
• ▪A second dose of vaccine or placebo was administered to 11,829 PreVenTB trial participants one month after the first dose.
• ▪12,295 participants in the PreVenTB trial completed 38 months of follow-up, representing 96.7% of those enrolled.
• ▪The PreVenTB trial enrolled 12,717 household contacts aged 6 years and older of recently diagnosed TB patients.
• ▪PreVenTB trial participants were randomly allocated to receive VPM1002, Immuvac, or placebo with 4,239 participants in each group.

Vaccine Efficacy Results Across Different TB Forms

• ▪VPM1002 showed 50.4% effectiveness against extrapulmonary tuberculosis across all age groups in the PreVenTB trial.
• ▪VPM1002 and Immuvac did not prevent latent tuberculosis infection in the PreVenTB trial.
• ▪VPM1002 and Immuvac did not offer general protection against tuberculosis in the PreVenTB trial.
• ▪VPM1002 and Immuvac demonstrated an ability to prevent the progression to active TB in those who developed latent TB.
• ▪VPM1002 showed 79.5% effectiveness against extrapulmonary tuberculosis in participants aged 36-60 years.

Age-Specific Protection and Nutritional Factors

• ▪VPM1002 provided protection against all tuberculosis, pulmonary tuberculosis, and extrapulmonary tuberculosis in children aged 6 to under 14 years.
• ▪VPM1002 and Immuvac did not protect children and adults who were underweight in the PreVenTB trial.

Safety Profile and Study Limitations

• ▪VPM1002 and Immuvac were found to be safe in the PreVenTB trial.
• ▪VPM1002 and Immuvac induced an immune response in the PreVenTB trial.
• ▪The COVID-19 pandemic sometimes delayed follow-ups in the PreVenTB trial.
• ▪The COVID-19 pandemic led to the exclusion of some PreVenTB trial participants who missed the second dose.

Perspective of Public health researchers focused on TB prevention

• ▪VPM1002's 79.5% effectiveness against extrapulmonary tuberculosis in middle-aged adults represents a significant finding for targeted vaccination strategies.
• ▪The PreVenTB trial's ability to prevent progression from latent to active tuberculosis suggests VPM1002 and Immuvac may have value in post-exposure prophylaxis.

Perspective of Vaccine developers and manufacturers

• ▪The safety profile demonstrated by VPM1002 and Immuvac across 12,717 participants supports continued development despite efficacy limitations.

Perspective of Underweight populations in TB-endemic regions

• ▪The failure of VPM1002 and Immuvac to protect underweight children and adults in the PreVenTB trial leaves nutritionally vulnerable populations without new prevention options.

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