Sunday, March 31, 2024

ECCMID 2024 Study: Mpox (monkeypox) Antibodies Wane Within A Year of Vaccination


 #17,977

While we await the next hoof to drop in the HPAI/cattle story, we've other infectious disease news of note. Yesterday, the European Society of Clinical Microbiology and Infectious Diseases published a press release on an upcoming presentation at next month's ECCMID 2024 meeting in Barcelona, Spain.

The Preliminary program lists the study as:

Mpox-specific antibodies wane within one year after MVA-BN vaccination

M.C. Shamier* (Rotterdam, Netherlands), L.P.M. Van Leeuwen, B.E. Verstrepen, K. Wijnans, N. Ahkiyate, H.M. Götz, R.D. De Vries, E.C.M. Van Gorp, M.P.G. Koopmans, S. Goeijenbier, C.H. Geurtsvankessel, L.M. Zaeck

This study found that recipients of the 2-Dose JYNNEOS/ IMVANEX/ IMVAMUNE mpox vaccine who did not receive a childhood smallpox vaccination (discontinued in the 1970s) experienced substantial drops in their immune response after 12 months. 

While the full report has yet to be published, we get early details from the following press release.  I'll have more after the break.

Study shows Mpox (monkeypox) antibodies wane within a year of vaccination

However antibodies remain high in those with pre-existing immunity

Reports and Proceedings

EUROPEAN SOCIETY OF CLINICAL MICROBIOLOGY AND INFECTIOUS DISEASES

New research to be presented at this year’s European Congress of Clinical Microbiology and Infectious Diseases (ECCMID 2024) in Barcelona, Spain (27-30 April) shows that the antibodies produced by Modified Vaccinia virus Ankara - Bavarian Nordic (MVA-BN) vaccination against mpox wane significantly within a year of receiving the vaccination – but in people with pre-existing immunity due to childhood smallpox vaccination in childhood, antibody levels remain high in almost all cases. The study is presented by PhD student Dr. Marc Shamier, Erasmus MC, Rotterdam, Netherlands, from a research team led by Dr Rory de Vries.

During the 2022-2023 mpox outbreak, MVA-BN was rapidly deployed among at-risk populations, including gay, bisexual, and other men who have sex with men (GBMSM). This vaccine is based on a highly attenuated strain of Vaccinia virus (VACV) – a virus that belongs to the orthopoxvirus genus, as do the viruses that cause smallpox (variola virus) and Mpox (monkeypox virus).

Little is known about the longevity of immune responses induced by-MVA-BN vaccination and the impact of prior smallpox vaccination. In this study, the authors assessed the antibody levels response to MVA-BN one year after vaccination. While marketed under various names such as JYNNEOS, IMVANEX, and IMVAMUNE, all are brand names for the same Modified Vaccinia Ankara (MVA)-based vaccine. As such, the immunological effects they confer are expected to be consistent across these products.

Out of the 118 vaccine recipients, 36 (30%) returned for the 1-year follow-up visit. Among individuals without pre-existing immunity, 14/21 (67%) had undetectable levels of VACV IgG and a 10.7-fold decrease in VACV IgG GMT (geometric mean, a standard measurement for antibody levels) was observed compared to the last time point after vaccination in 2022 (4 weeks after the second dose) (Figure 1 full abstract).

In contrast, among individuals with childhood smallpox vaccination, only one participant out of 15 (7%) had undetectable VACV IgG after one year, and the GMT reduction between 4 weeks after the last vaccine dose in 2022 and the one-year follow-up visit was 2.5-fold for those vaccinated with two doses of MVA-BN, and 1.9-fold for those vaccinated with one dose of MVA-BN.

The authors say: “A rapid decline in VACV-specific IgG antibodies was observed one year after MVA-BN vaccination, leading to loss of detectable antibodies in 42% (15/36) of the participants. This reduction was most pronounced in individuals without pre-existing immunity. As the mechanism of protection for mpox remains undefined, the implications of waning antibody levels for conferring protection remain uncertain.

The authors suggest that the decrease in antibodies over time following MVA-BN vaccination may be attributable its composition. They say: “The first and second-generation smallpox vaccines contained replication-competent vaccinia virus. MVA-BN is based on non-replicating virus, which may impact the strength and duration of the immune response; with the advantage of a low risk of side effects.”

They add: “Regarding the potential necessity for a booster, it is premature to draw such conclusions. It is unclear how waning antibody levels relate to protection. Immunity also involves other elements, such as T-cell responses. Comprehensive clinical monitoring over time, which connects infection rates with antibody levels, is required to make informed decisions about booster vaccination protocols.”
Admittedly, the JYNNEOS vaccine - which was first approved in 2019 - was never expected to be 100% protective against Mpox (see MMWR: Five Recent Reports On Mpox Outbreaks & Vaccine Effectiveness), and the CDC has previously acknowledged:

Peak immunity is expected to be reached 14 days after the second dose of JYNNEOS vaccine. The duration of immunity after one or two doses of JYNNEOS is currently unknown.

While the waning of detectable antibodies after a year is disappointing - it is still possible that some degree of protection remains - particularly against severe disease. 

Although the global health emergency over the international spread of a new clade (IIb) of Mpox (formerly Monkeypox) was declared over 11 months ago, we continue to see sporadic infections around the globe, while a more dangerous clade I mpox virus continues to rage ( > 12,000 cases in 2023) in the DRC.

Four months ago, the WHO Reported the 1st Confirmed Cluster Of Sexually Transmitted MPXV Clade 1 in the DRCwarning that `The risk of mpox further spreading to neighbouring countries and worldwide appears to be significant.'

Earlier this month we looked at a report in Eurosurveillance: Ongoing Mpox Outbreak in South Kivu Province, DRC Associated With a Novel Clade I Sub-lineage, which contained the first genomic analysis of samples from a previously unaffected region of the DRC. 

This study revealed a novel clade I sub-linage had emerged - most likely from a zoonotic introduction - with changes that may render current CDC tests unreliable.

Like all viruses, Monkeypox continues to evolve and diversify, as discussed in the 2014 EID Journal article Genomic Variability of Monkeypox Virus among Humans, Democratic Republic of the Congo, where the authors cautioned:

Small genetic changes could favor adaptation to a human host, and this potential is greatest for pathogens with moderate transmission rates (such as MPXV) (40). The ability to spread rapidly and efficiently from human to human could enhance spread by travelers to new regions.
While Mpox has largely fallen out of the news cycle, it hasn't gone away.  And given its ability to reinvent itself over time, could easily begin another world tour.