Swedish study indicates a significant decline of neutralising antibodies to monkeypox virus already during the first month after vaccination
Highlights the need for a clinical trial of a booster dose before any policy decision
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 even in men who receives two doses of mpox vaccine intradermally, their level of antibodies to the virus falls to low or zero within the first few months if they have not received a previous smallpox vaccine.
The authors, who include Dr Klara Sonden, deputy state epidemiologist of the of Public Health Agency of Sweden and affiliated to Karolinska Institute, Stockholm, Sweden, says that their study shows that booster vaccination may be needed long-term for such individuals, and that scientific evidence is needed for the background to any decisions.
Since May 2022, an mpox outbreak has emerged globally, spreading mainly among men who have sex with men (MSM). It was classified as a Public Health Emergency of International Concern (PHEIC). In Sweden, a vaccine against smallpox based on the live Modified Vaccinia Virus Ankara (MVA-BN), has been offered intradermally to risk groups. Intradermal administration means 0.1 ml in the skin, one fifth of the dose needed for subcutaneous administration. This was used as a dose-saving strategy as supplies were initially limited.
The vaccine has been shown to be efficacious in studies using real-world data from the 2022 and onward outbreak among MSM, with limited number of breakthrough infections and milder disease reported when breakthrough infections occur so far. The aim of this cohort study was to assess dynamics of, and factors affecting neutralising antibodies against mpox virus (MPXV) following MVA-BN vaccination.
A total of 100 MSM attending the sexual health clinic “Venhälsan”, Stockholm, Sweden, eligible to receive the vaccine MVA-BN were included in the study. Following the initial serum sample drawn before dose 1, serum samples were further collected before dose 2, and 28 days and three months after the second dose. These samples were tested to establish titers (levels) of MPXV-neutralising antibodies. Titers were compared in individuals with or without previous smallpox vaccination and patients with past natural infection were included as positive controls.
10 individuals were of uncertain status regarding smallpox vaccination (due to being born in many different countries in the time period 1977-1980 when vaccination was de-escalated globally) and 23 individuals were previously smallpox vaccinated. The other 67 individuals had no history of smallpox vaccination.
A total of 312 samples from four time points from the 100 individuals included in the study were analysed. In addition to the study population, anonymised age and sex matched controls from blood donors were included as negative controls (n=20) and previously MPXV-infected individuals as positive controls (n=20). The controls gave one blood sample each.
Within the study group, previous smallpox vaccination was associated with significantly higher antibody titers, and 15/23 of these individuals had pre-existing neutralising antibodies (ie, the B-cell memory was still present thanks to their previous smallpox vaccination).
Among those without prior smallpox vaccination, fewer than half of the group showed any detectable neutralizing antibodies at all 28 days after the second vaccination, with those who did exhibit responses having a median titer (standard unit of measurement of antibodies) of 20. In contrast, for previously vaccinated individuals, the median titer 28 days after a single dose of the MVA-BN vaccine was 40.
The authors say: “Our findings corroborate other studies showing that mpox vaccination results in neutralising antibodies only in a proportion of vaccinees, and that a significant decline occurs already during the first month post-vaccination Immunity after previous MPXV infection mounts a higher and more robust neutralising response. In conclusion, the findings merits the study of booster doses.”
They continue: “Our results indicate a rapid decline in neutralising antibodies after two doses and are in line with other recent studies. These results, together with the continued spread of mpox in MSM populations in Europe has prompted the consideration of a booster dose. Such a recommendation needs to be based on scientific evidence. However, as far as we know, no clinical trial has studied or is studying a 3rd MVA-BN dose (from an analysis of clinicaltrials.gov March 2024), but a booster dose is common practice for inactivated vaccines. The MVA-BN is a live, non-replicating vaccine and therefore likely equivalent to an inactivated vaccine. Studies are essential to inform public health policy, and the largest STI clinic in Sweden is planning to perform a randomised clinical trial of a booster dose with immunological parameters as the primary outcome in the comparison with those who have had the two doses of the regular full 0.5 subcutaneous dose (sc) (0.5ml), two doses of the dose-saving intradermal dose (id) (0.1ml), or one dose sc/one dose id, and those with no booster dose.”
They add that despite this, the Mpox cases in Sweden have been few and mostly imported during 2023 (12 cases) and 2024 (5 cases) and the vast majority have been among unvaccinated individuals. Data collection is ongoing regarding the occurrence of breakthrough infections in Sweden. Breakthrough cases have been reported in the scientific literature among individuals that have received different vaccination strategies (i.e. sc/sc, id/sc, id/id) (Hazra et al)*.
Dr Sonden concludes: “The results presented here indicate that long-term protective immunity might need a booster dose for its maintenance. Since the current situation regarding mpox in Sweden is stable with minimal transmission any change in policy should be backed by results from clinical trials. Currently we will focus on finding unvaccinated individuals who are at risk of getting mpox and offer them vaccination, and we believe that this as well as the previously administered vaccinations will contribute to lowering the risk for new outbreaks of mpox in Sweden in future.”
ARTICLE PUBLICATION DATE
30-Mar-2024
Study shows Mpox (monkeypox) antibodies wane within a year of vaccination
However antibodies remain high in those with pre-existing immunity
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.”
ARTICLE PUBLICATION DATE
30-Mar-2024
Case report from Austria shows mpox breakthrough infection in man who had received both vaccine doses
A second case is currently under investigation
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) details the case of a man who had received two doses of the monkey pox vaccine in Autumn, 2022 yet experienced a ‘breakthrough’ mpox infection in January 2024. The authors believe breakthrough should be considered in fully vaccinated individuals engaging in high-risk behaviors. They also call for further research on the need for booster doses to protect against these breakthrough infections. The case report is by Dr Luigi Segagni-Lusignani, Public Health Authority, Vienna, Austria and colleagues. They add a second case, reported in the last few weeks (March 2024) is currently under investigation.
Following the sharp decline in notifications of new mpox infections after introducing the EMA-approved modified Vaccinia Ankara–Bavarian Nordic (MVA-BN) administration in late 2022 and early 2023, an upsurge in mpox cases occurred in the latter half of 2023 in European countries. Clusters were observed in individuals presumed immune through recent vaccination, but data on the durability of protective immunity after complete 2-dose vaccination are limited.
The authors here present a case of mpox infection in a 35-year-old, who had completed the two-dose course of intradermal third-generation Jynneos vaccine as pre-Exposure Prophylaxis (PrEP) on November 8, 2022, with a 28-day interval between the first and second dose. His medical history included well-controlled HIV infection since 2011 (CD4 count of > 700 cells/µL), hepatitis C infection in April 2017, SARS-CoV-2 infection in November 2020, and Campylobacter infections in August 2021 and January 2022.
In January 2024, five days after multiple sexual encounters during a Vienna event, the patient reported fever, chills, headache, discomfort urinating, diarrhoea with bleeding, and penile and anal itching. On day 3, a genital herpes infection was suspected, but no treatment was started. After two days, he presented to the dermatology clinic with worsening lymphadenopathy (swollen lymph nodes), where positive mpox virus PCR results were obtained. His Mpox Severity Score System (MPOX-SSS) was 10 (of a maximum score of 12).
No antiviral treatment was administered, no hospitalisation was required and the patient was home isolated. After 21 days, a control swab was still positive and the isolation had to be extended to day 25 from symptom onset, when finally all scabs fell off the lesions and PCR test on viral swab was negative.
The authors say: “This was Austria's first mpox breakthrough case. Despite no hospitalisation, the clinical course was not less severe than in unvaccinated patients, with longer disease duration and higher scores on the mpox severity scale. The 14-month interval between complete vaccination and infection suggests vaccine-induced immunity could be not durably protective. This case underscores the importance of clinical suspicion for mpox in high-risk groups, even if fully vaccinated with 2-doses. Breakthrough infections need to be explored further, as well as the possibility of vaccine boosters in vaccinated groups with epidemiological risky behaviours.”
They add: “The Austrian Vaccine Board updates its national mpox vaccine strategy annually based on new scientific evidence. Currently, there is no nationwide recommendation for booster shots after completing the currently recommend (Jynneos) vaccination regimen, even for high-risk groups. However, any potential changes to the vaccination strategy will depend on filling critical knowledge gaps in mpox immunity. These gaps include understanding the current level of immunity, the durability of immune responses, and the long-term vaccine effectiveness in high-risk groups.”
A second case is currently under investigation
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) details the case of a man who had received two doses of the monkey pox vaccine in Autumn, 2022 yet experienced a ‘breakthrough’ mpox infection in January 2024. The authors believe breakthrough should be considered in fully vaccinated individuals engaging in high-risk behaviors. They also call for further research on the need for booster doses to protect against these breakthrough infections. The case report is by Dr Luigi Segagni-Lusignani, Public Health Authority, Vienna, Austria and colleagues. They add a second case, reported in the last few weeks (March 2024) is currently under investigation.
Following the sharp decline in notifications of new mpox infections after introducing the EMA-approved modified Vaccinia Ankara–Bavarian Nordic (MVA-BN) administration in late 2022 and early 2023, an upsurge in mpox cases occurred in the latter half of 2023 in European countries. Clusters were observed in individuals presumed immune through recent vaccination, but data on the durability of protective immunity after complete 2-dose vaccination are limited.
The authors here present a case of mpox infection in a 35-year-old, who had completed the two-dose course of intradermal third-generation Jynneos vaccine as pre-Exposure Prophylaxis (PrEP) on November 8, 2022, with a 28-day interval between the first and second dose. His medical history included well-controlled HIV infection since 2011 (CD4 count of > 700 cells/µL), hepatitis C infection in April 2017, SARS-CoV-2 infection in November 2020, and Campylobacter infections in August 2021 and January 2022.
In January 2024, five days after multiple sexual encounters during a Vienna event, the patient reported fever, chills, headache, discomfort urinating, diarrhoea with bleeding, and penile and anal itching. On day 3, a genital herpes infection was suspected, but no treatment was started. After two days, he presented to the dermatology clinic with worsening lymphadenopathy (swollen lymph nodes), where positive mpox virus PCR results were obtained. His Mpox Severity Score System (MPOX-SSS) was 10 (of a maximum score of 12).
No antiviral treatment was administered, no hospitalisation was required and the patient was home isolated. After 21 days, a control swab was still positive and the isolation had to be extended to day 25 from symptom onset, when finally all scabs fell off the lesions and PCR test on viral swab was negative.
The authors say: “This was Austria's first mpox breakthrough case. Despite no hospitalisation, the clinical course was not less severe than in unvaccinated patients, with longer disease duration and higher scores on the mpox severity scale. The 14-month interval between complete vaccination and infection suggests vaccine-induced immunity could be not durably protective. This case underscores the importance of clinical suspicion for mpox in high-risk groups, even if fully vaccinated with 2-doses. Breakthrough infections need to be explored further, as well as the possibility of vaccine boosters in vaccinated groups with epidemiological risky behaviours.”
They add: “The Austrian Vaccine Board updates its national mpox vaccine strategy annually based on new scientific evidence. Currently, there is no nationwide recommendation for booster shots after completing the currently recommend (Jynneos) vaccination regimen, even for high-risk groups. However, any potential changes to the vaccination strategy will depend on filling critical knowledge gaps in mpox immunity. These gaps include understanding the current level of immunity, the durability of immune responses, and the long-term vaccine effectiveness in high-risk groups.”
ARTICLE PUBLICATION DATE
30-Mar-2024
30-Mar-2024
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