Medichealthy The New Generation of TB Vaccine is Ineffective - Medichealthy The New Generation of TB Vaccine is Ineffective

The New Generation of TB Vaccine is Ineffective

Recently, a Cochrane review analyzed the efficacy of a new generation of tuberculosis (TB) vaccine, the MVA85A vaccine. The MVA85A vaccine was added to the BCG vaccine in order to increase the preventing effect of the disease.

The New Generation of TB Vaccine is Ineffective
Source Picture: https://www.irishtimes.com


Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis. Although the number of deaths from tuberculosis decreased by 22% between 2000 and 2015, tuberculosis was still ranked as the 10th highest cause of death in the world in 2016.

Current TB Vaccine and its Disadvantages

The Bacillus Calmette-Guérin (BCG) vaccine is currently a tuberculosis vaccine available. Studies show that the vaccine has an excellent protective effect against tuberculosis in children, especially in more severe forms of the disease, such as tuberculosis meningitis or miliary tuberculosis.

The efficacy of BCG is reported to be very different, depending on the infection location. The BCG vaccine provides proper protection against meningitis and miliary tuberculosis in children but provides variable protection against pulmonary TB. Thus, even though many areas have a high vaccination coverage, the incidence of tuberculosis remains a problem. Therefore, various studies have been conducted to find a new generation of vaccines with better tuberculosis prevention efficacy.

New Generation TB Vaccines

The modified Vaccinia Ankara virus-expressing antigen 85A (MVA85A) is a weakened virus that does not replicate in human tissue and encodes many antigens, thus allowing the development of multivalent vaccines.

As a vaccine for tuberculosis, MVA has DNA fragments from M tuberculosis, thus expressing 85A antigens. This antigen complex will disrupt the enzyme involved in tuberculosis bacterial cell wall biosynthesis. The enzyme plays a role in forming mycoplasma membranes, which is vital for bacterial survival because they function as an effective barrier against antibiotics.

Immunological studies indicate that MVA85A can be used to enhance the effects of the BCG vaccine because MVA85A is thought to be effective in expanding the specific immune response against M tuberculosis.

Research on New Generation of TB Vaccine

A Phase 2b clinical trial published in The Lancet in 2013 tried to analyze the safety, immunogenicity, and efficacy of MVA85A against tuberculosis infection in infants. This research was conducted with a monitoring period of 3-39 months and involved 2797 infants. The study found that some severe and systemic side effects did not differ significantly between the case and control groups. This study concluded that MVA85A is well tolerated and able to induce cellular immune responses to a moderate degree. However, no efficacy was associated with infection or disease due to M. tuberculosis.

Another Phase 2 clinical trial was published in 2015. This study aims to analyze the safety, immunogenicity, and efficacy of MVA85A in preventing tuberculosis in adult patients with HIV. The study was conducted for 46 months with the endpoints of the study being active TB and latent TB. The results showed no significant difference after the MVA85A vaccine against the incidence of active TB infection and latent TB. This study concluded that MVA85A is well tolerated and is immunogenic in adult patients with HIV. Still, there is no efficacy to infection or disease due to M. tuberculosis.

A more recent Phase 2 clinical trial was a study by Nemes et al. Published in 2018. This study analyzed the safety and immunogenicity of MVA85A combined with the BCG vaccine in infants born to HIV mothers. The study was conducted for 46 months with the endpoints of the study being active TB and latent TB. The results showed no significant difference in the incidence of active TB infection and latent TB after the MVA85A vaccine was given.

The study's results above were supported by the latest Cochrane Review and published at the end of April 2019. This study analyzed various clinical trials that provide the MVA85A vaccine with BCG, regardless of HIV status. The analysis proved that MVA85A given intradermally in addition to the BCG vaccine is safe but not effective in reducing the risk of tuberculosis.

Conclusion
The BCG vaccine is a tuberculosis vaccine that is widely used today. However, the BCG vaccine has different efficacy depending on the patient's age and the location of the infection. Therefore, the new generation vaccine, MVA85A, was studied in hopes of increasing the protective effect of the BCG vaccine against tuberculosis. Unfortunately, many existing studies prove that this new generation of vaccine is not effective in reducing the risk of tuberculosis.


References
1. World Health Organization. Global tuberculosis report 2018. www.who.int/tb/publications/global_report/en/ (accessed 28 Juni 2018)
2. Roy A, Eisenhut M, Harris RJ, Rodrigues LC, Sridhar S, Habermann S, et al. Effect of BCG vaccination against Mycobacterium tuberculosis infection in children: systematic review and meta‐analysis. BMJ 2014;349:g4643. [DOI: 10.1136/bmj.g4643]
3. Altenburg AF, Kreijtz JH, Vries RD, Song F, Fux R, Rimmelzwaan GF, et al. Modified vaccinia virus ankara (MVA) as production platform for vaccines against influenza and other viral respiratory diseases. Viruses 2014;6(7):2735‐61.
4. Kashangura R, Julien S, Garner P, Johnson S. MVA85A vaccine to enhance BCG for preventing tuberculosis. CochraneDatabase of Systematic Reviews 2019, Issue 4. Art. No.: CD012915. DOI: 10.1002/14651858.CD012915.pub2.
5. Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, et al. Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomized, placebo-controlled phase 2b trial. Lancet 2013;381(9871):1021–8.
6. Ndiaye BP, Thienemann F, Ota M, Landry BS, Camara M, Dièye S, et al. Safety, immunogenicity, and efficacy of the candidate tuberculosis vaccine MVA85A in healthy adults infected with HIV-1: a randomized, placebo-controlled, phase 2 trial. Lancet Respiratory Medicine 2015;3(3): 190–200.
7. Nemes E, Hesseling A, Tameris M, Mauff K, Downing K, Mulenga H, et al. Safety and immunogenicity of newborn MVA85A vaccination and selective, delayed Bacille Calmette-Guerin (BCG) for infants of HIV infected mothers: a Phase 2 randomized controlled trial. Clinical Infectious Diseases 2018;66(4):554–63. DOI: 10.1093/cid/cix834

Post a Comment

0 Comments