Chinese researchers warn that current vaccines are inefficient in protecting against emerging Mpox virus

Mpox News: Understanding the Vaccinia Virus and Monkeypox Challenge
The ongoing outbreak of monkeypox, driven by a new strain of the Mpox virus, has raised significant concerns globally, particularly in China. Researchers from various leading institutions, including the Wuhan Institute of Virology, Chinese Academy of Sciences, and Guangzhou Medical University, have conducted a study to assess whether the Vaccinia Virus Tiantan (VTT) strain, traditionally used as a smallpox vaccine, can effectively elicit immunity against the emerging monkeypox virus. This Mpox News report explores the findings of this important study and its implications for public health.

Chinese researchers warn that current vaccines are inefficient in protecting against
emerging Mpox virus

The smallpox vaccine, developed from the Vaccinia virus, was a cornerstone in the global eradication of smallpox. With the resurgence of monkeypox, a related Orthopoxvirus, the question arises whether the same vaccine can protect against this new threat. The study conducted by these esteemed researchers sought to answer this question by investigating the cross-reactive immunity generated by the VTT strain against the emerging monkeypox virus strain Clade IIb, isolated in Wuhan, China, in 2023.
 
Study Overview: Examining the Efficacy of VTT Against Monkeypox
The study employed a rigorous experimental design involving the immunization of six-week-old female BALB/c mice with varying doses of VTT. The mice were vaccinated intraperitoneally with 1 × 10^4, 1 × 10^5, and 1 × 10^6 plaque-forming units (PFUs) of VTT. After 21 days, the mice received a booster dose, and their sera and splenocytes were collected to analyze the humoral and cellular immune responses.
 
The key aim was to determine if the VTT strain could elicit cross-neutralizing antibodies (cNAb) against the emerging monkeypox virus. The researchers performed a plaque reduction neutralization test (PRNT) to evaluate the neutralization activity of the serum against both VTT and the monkeypox virus. The results revealed a concerning finding: the VTT strain was inefficient in inducing cNAb against the monkeypox virus, even at higher doses.
 
Key Findings: Limited Cross-Reactive Immunity
The study's findings highlighted the inefficiency of the VTT strain in generating a robust immune response against the monkeypox virus. Specifically, at the standard dose of 1 × 10^4 PFUs, the geometric mean titer (GMT) of neutralizing antibodies (NAb) against VTT was 17.9, while cNAb against the monkeypox virus was undetectable. Even when the dose was increased tenfold, the GMT of monkeypox cNAb was only 9.7, significantly lower than the GMT of VTT NAb, which reached 42.9.
 
These findings suggest that a much higher dose of VTT is required to elicit any detectable level of monkeypox cNAb compared to the dose needed for VTT NAb. However, even at the highest dose of 1 × 10^6 PFUs, the GMT of monkeypox cNAb was 17.1, still six times lower than that of VTT NAb (108.5). This significant reduction in the efficiency of VTT to induce cross-reactive immu nity against the monkeypox virus indicates that the VTT strain may not be a suitable vaccine candidate for monkeypox.
 
Comparative Analysis: VTT vs. Other Smallpox Vaccines
The study also compared the VTT strain with other smallpox vaccines, such as Dryvax, which was widely used in the Smallpox Eradication Program (SEP). While Dryvax, derived from Vaccinia virus, was found to induce cNAb against Variola virus (the causative agent of smallpox) with only a 1.3-fold reduction compared to VTT, the VTT strain showed a more than six-fold reduction in efficiency when it came to inducing monkeypox cNAb. This comparison underscores the limited potential of VTT as a viable option for monkeypox vaccination.
 
Further evidence supporting the inefficacy of Vaccinia-based vaccines for monkeypox comes from the U.S. FDA-approved monkeypox vaccine, MVA-BN which is also promoted by the WHO. This replication-deficient Vaccinia strain induced detectable monkeypox cNAb in only 63% of recipients after two doses. The findings suggest that Vaccinia virus-based vaccines, including VTT, are more suited for smallpox and may not offer adequate protection against monkeypox.
 
Cellular Immune Response: A Disappointing Outcome
In addition to humoral immunity, the study also examined the cellular immune response induced by VTT. The researchers conducted an IFN-γ ELISpot assay to assess the number of IFN-γ secreting cells in the spleens of vaccinated mice. The results were similarly disappointing. The median number of spot-forming cells (SFCs) was 177 per 10^5 cells after exposure to VTT but dropped dramatically to 19 SFCs per 10^5 cells when exposed to the monkeypox virus. Even at the highest vaccination dose, there was only a slight increase in SFCs, indicating that VTT is also inefficient in eliciting cross-reactive cellular immunity against the monkeypox virus.
 
Implications for Public Health: The Need for New Vaccines
The study’s findings have significant implications for public health, particularly in China, where over 96% of monkeypox cases have been reported among men who have sex with men (MSM). A considerable portion of this population is also living with HIV, making them ineligible for vaccination with replication-competent Vaccinia virus strains like VTT due to the risk of systemic infection.
 
Given the inefficiency of VTT in eliciting cross-reactive immunity against the emerging monkeypox virus strain, there is an urgent need to develop new and more effective vaccines. The findings of this study highlight the limitations of relying on older vaccines for emerging infectious diseases and underscore the importance of ongoing research and development in vaccine technology.
 
Conclusion: A Call for Better Preparedness
In conclusion, the study findings reveal the inefficiency of the Vaccinia Virus Tiantan strain in protecting against the emerging monkeypox virus. The limited cross-reactive immunity, both humoral and cellular, suggests that VTT may not be an adequate solution for the current monkeypox outbreak. As the world faces the ongoing threat of monkeypox, there is a pressing need for the development of new vaccines that can provide better protection and ensure global health security.
 
The study findings were published as a correspondence in the peer-reviewed journal: Emerging Microbes & Infections.
https://www.tandfonline.com/doi/full/10.1080/22221751.2024.2306967
 
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