BioNTech's mRNA Monkeypox Vaccine Shows Excellent Preclinical Data

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BioNTech’s mRNA Monkeypox Vaccine Shows Excellent Preclinical Data

BioNTech’s mRNA Monkeypox Vaccine Shows Excellent Preclinical Data

Since May 2022, a monkeypox outbreak has erupted globally, infecting over 90,000 people in 115 countries and territories.

This typical zoonotic infectious disease has been spreading for years in West and Central Africa, but the 2022 outbreak was driven by unprecedented human-to-human transmission, leading the World Health Organization (WHO) to declare it a Public Health Emergency of International Concern (PHEIC) in July 2022. The PHEIC was subsequently terminated as case numbers declined.

However, in 2023, a second large-scale independent outbreak occurred in the Democratic Republic of the Congo (DRC), with reports of high mortality rates.

These outbreaks illustrate the potential for monkeypox virus reemergence and spread, highlighting limitations in current vaccine supply.

Monkeypox virus (MPXV) is the pathogen responsible for monkeypox and belongs to the Orthopoxvirus genus, similar to the variola virus (VARV) that causes smallpox. Monkeypox typically manifests as a self-limiting infection, with symptoms including fever, headache, fatigue, lymph node swelling, and skin lesions. However, infections can also be fatal, most commonly with the I-type MPXV infection. The 2022 global monkeypox outbreak was caused by the IIb-type MPXV, which typically results in milder symptoms, while the 2023 outbreak in the DRC was caused by the I-type MPXV.

Orthopoxviruses have a double-stranded DNA genome, and their antigens share high similarity, allowing immune responses to one virus to provide cross-protective immunity against other viruses within the Orthopoxvirus genus. This cross-protection was previously exploited with the use of vaccinia virus (VACV) as a live virus vaccine, leading to the eradication of smallpox. Early VACV immunization provided robust and lasting protection against both smallpox and monkeypox but had adverse effects, limiting its use in certain populations. Current third-generation vaccines are based on the modified vaccinia Ankara virus (MVA), a non-replicating VACV derivative with improved safety.

Although the MVA vaccine has been available since before May 2022, stockpiles and existing production capacity were insufficient to meet the demands of the 2022 outbreak, necessitating vaccine allocation. Additionally, during the 2022 outbreak, the effectiveness of receiving two doses of the MVA vaccine was estimated at only 66%, with antibody responses rapidly waning within two years.

Therefore, there is a need for a new, potent, durable, and safe monkeypox vaccine, particularly one that can be rapidly mass-produced and globally distributed. mRNA vaccine giant BioNTech initiated the BNT166 project in May 2022, aiming to develop a next-generation mRNA-based monkeypox vaccine to combat monkeypox virus and related Orthopoxviruses.

On February 15, 2024, researchers from mRNA vaccine company BioNTech published a study titled “A multivalent mRNA monkeypox virus vaccine (BNT166) protects mice and macaques from orthopoxvirus disease” in the top-tier academic journal Cell.

The study confirmed that the multivalent mRNA monkeypox vaccine (BNT166) produced 100% protection against Orthopoxvirus infection, including monkeypox virus, in mice and crab-eating macaques. These data support the ongoing clinical trials of BioNTech’s multivalent mRNA monkeypox vaccine.

BioNTech's mRNA Monkeypox Vaccine Shows Excellent Preclinical Data

Orthopoxviruses have two different forms of infection, mature virion (MV) and extracellular virion (EV), each with a unique set of surface antigens. While immune responses against single antigens can provide some protection, targeting antigens from both forms of the virus simultaneously can lead to better protection.

BNT166 encodes surface antigen proteins from both EV (A35, B6) and MV (M1 and H3) forms of the monkeypox virus. The selection of these antigens was based on three factors. Firstly, these antigens are immunogenic following natural exposure to variola or monkeypox viruses, confirmed targets of protective immune responses. Secondly, these antigens are conserved across many Orthopoxviruses, increasing the likelihood of cross-protection. Finally, these antigens are suitable for the mRNA platform.

To address the multiple forms of monkeypox virus and increase the breadth of immune responses, BioNTech evaluated two candidate multivalent mRNA monkeypox vaccines in preclinical studies, a quadrivalent vaccine BNT166a (encoding monkeypox virus antigens A35, B6, M1, H3), and a trivalent vaccine BNT166c (encoding monkeypox virus antigens A35, B6, M1).

Both candidate mRNA monkeypox vaccines induced robust T-cell responses and IgG antibodies in mice, including neutralizing antibodies against monkeypox virus and vaccinia virus. In virus challenge experiments, BNT166a and BNT166c provided complete protection against vaccinia virus, MPXV I-type, and MPXV IIb.

Furthermore, in crab-eating macaques, vaccination with BNT166a demonstrated 100% efficacy in preventing death and suppressing fatal I-type monkeypox virus infection. These findings support the clinical evaluation of BNT166, with the current clinical trial registered as NCT05988203.