Cross-Neutralizing and Protective Human Antibody Specificities to Poxvirus Infections.

Monkeypox (MPXV) and cowpox (CPXV) are emerging agents that cause severe human infections on an intermittent basis, and variola virus (VARV) has potential for use as an agent of bioterror. Vaccinia immune globulin (VIG) has been used therapeutically to treat severe orthopoxvirus infections but is in short supply. We generated a large panel of orthopoxvirus-specific human monoclonal antibodies (Abs) from immune subjects to investigate the molecular basis of broadly neutralizing antibody responses for diverse orthopoxviruses. Detailed analysis revealed the principal neutralizing antibody specificities that are cross-reactive for VACV, CPXV, MPXV, and VARV and that are determinants of protection in murine challenge models. Optimal protection following respiratory or systemic infection required a mixture of Abs that targeted several membrane proteins, including proteins on enveloped and mature virion forms of virus. This work reveals orthopoxvirus targets for human Abs that mediate cross-protective immunity and identifies new candidate Ab therapeutic mixtures to replace VIG.

Mpox-specific immune responses elicited by vaccination or infection in people living with HIV.

In the recent mpox outbreak, people living with HIV (PLWH) were at high risk both for contracting infection and for suffering a more severe disease course. We studied cellular and humoral immune responses elicited by mpox infection (n = 5; n = 3 PLWH) or smallpox vaccination (n = 17; all PLWH) in a cohort of men who have sex with men. All PLWH were successfully treated, with stable CD4 counts and undetectable HIV viral loads. 11/17 vaccinated individuals had received childhood smallpox vaccination. In this group of individuals, both two-dose MVA-vaccination and natural infection evoked mpox-specific immune responses mediated by B cells as well as CD4 and CD8 T cells. This study improves our understanding of smallpox vaccination mediated cross-reactivity to other orthopox viruses, and the long-lasting durability of childhood smallpox vaccination mediated immune responses including in PLWH.

Serological responses to smallpox A33 antigen and monkeypox A35 antigen in healthy people and people living with HIV-1 from Guangzhou, China.

People are expected to have been previously vaccinated with a Vaccinia-based vaccine, as until 1980 smallpox vaccination was a standard protocol in China. It is unclear whether people with smallpox vaccine still have antibody against vaccinia virus (VACV) and cross-antibody against monkeypox virus (MPXV). Herein, we assessed the binding antibodies with antigen of VACV-A33 and MPXV-A35 in the general population and HIV-1 infected patients. Firstly, we detected VACV antibody with A33 protein to evaluate the efficiency of smallpox vaccination. The result show that 29% (23 of 79) of hospital staff (age ≥ 42 years) and 63% (60 of 95) of HIV-positive patients (age ≥ 42 years) from Guangzhou Eighth People's Hospital were able to bind A33. However, among the subjects below 42 years of age, 1.5% (3/198) of the hospital volunteer samples and 1% (1/104) of the samples from HIV patients were positive for antibodies against A33 antigen. Then, we assessed the specific cross-reactive antibodies against MPXV A35 protein. 24% (19 of 79) hospital staff (age〉 = 42 years) and 44% (42 of 95) of HIV-positive patients (age〉 = 42 years) were positive. 98% (194/198) of the hospital staff and 99% (103/104) of the HIV patients had no A35-binding antibodies. Further, we found significant sex differences for the reactivity to A35 antigen were observed in HIV population, but no significant sex differences in hospital staff. Further, we analyzed the positivity rate of anti-A35 antibody of men who have sex with men (MSM) and non-MSM in HIV patients (age〉 = 42years). We found that 47% of no-MSM population and 40% of MSM population were positive for A35 antigen, with no significant difference. Lastly, we found only 59 samples were positive for anti-A33 IgG and anti-A35 IgG in all participants. Together, we demonstrated A33 and A35 antigens binding antibodies were detected in HIV patients and general population who were older than 42 years, and cohort studies only provided data of serological detection to support early response to monkeypox outbreak.

Post-exposure vaccine effectiveness and contact management in the mpox outbreak, Madrid, Spain, May to August 2022.

BackgroundAppropriate vaccination strategies have been key to controlling the outbreak of mpox outside endemic areas in 2022, yet few studies have provided information on mpox vaccine effectiveness (VE).AimTo assess VE after one dose of a third-generation smallpox vaccine against mpox when given as post-exposure prophylaxis (PEP) within 14 days.MethodsA survival analysis in a prospective cohort of close contacts of laboratory-confirmed mpox cases was conducted from the beginning of the outbreak in the region of Madrid in May 2022. The study included contacts of cases in this region diagnosed between 17 May and 15 August 2022. Follow up was up to 49 days. A multivariate proportional hazard model was used to evaluate VE in the presence of confounding and interaction.ResultsInformation was obtained from 484 close contacts, of which 230 were vaccinated within 14 days of exposure. Of the close contacts, 57 became ill during follow-up, eight vaccinated and 49 unvaccinated. The adjusted effectiveness of the vaccine was 88.8% (95% CI: 76.0-94.7). Among sexual contacts, VE was 93.6% (95% CI: 72.1-98.5) for non-cohabitants and 88.6% (95% CI: 66.1-96.2) for cohabitants.ConclusionPost-exposure prophylaxis of close contacts of mpox cases is an effective measure that can contribute to reducing the number of cases and eventually the symptoms of breakthrough infections. The continued use of PEP together with pre-exposure prophylaxis by vaccination and other population-targeted prevention measures are key factors in controlling an mpox outbreak.

[Management from Primary Care of monkeypox infection (MPOX) in humans]. / Manejo desde atención primaria de la infección por la viruela del mono (MPOX) en humanos.

Monkeypox (MPOX) is a viral zoonosis endemic in West or Central African countries that is sporadically exported to another area. In May 2022, a global outbreak of MPOX smallpox began to occur in several countries in Europe and North America. Most of the reported cases are identified at the outpatient level and mainly affect men who have sex with men (MSM). Transmission is by close contact with lesions, body fluids, respiratory secretions or contaminated material from an infected person or animal. The clinical picture is similar to human smallpox, with less severity. Mild, self-limiting skin involvement predominates after 2-4 weeks. In MSM, atypical skin lesions appear due to the mode of infection. Severe forms or complications may appear in certain risk groups. The case fatality rate is 3%-6% depending on the clade responsible. The diagnosis of suspicion is confirmed by detection of the virus from exudates of lesions or scabs, with nucleic acid amplification techniques by conventional or real-time PCR. Clinical management in most cases is performed in primary care (PC), by monitoring the main symptoms. Between 5-10% require hospital management and there are some specific antiviral treatment options. Human smallpox vaccines protect against MPOX and are used as pre- and post-exposure prophylaxis for persons at risk. Measures to reduce exposure to the virus are the main MPOX prevention strategy. In addition, the role of the family physician is key to controlling the spread of MPOX through active surveillance and early diagnosis of the disease.

Monkeypox in Patient Immunized with ACAM2000 Smallpox Vaccine During 2022 Outbreak.

We report a case of monkeypox in the United States in a patient who had been vaccinated with ACAM2000 smallpox vaccine 8 years earlier. Despite his vaccination status, he still contracted disease. He showed prodromal symptoms preceding development of painless penile lesions that later coalesced.

Monkeypox Vaccination in the Republic of Korea: Identifying the High-Risk Target Group.

In June 2022, the first monkeypox case was reported as imported into Korea. The general public asked whether they should get vaccinated against monkeypox because of the recent COVID-19 vaccination experience. As of the current monkeypox outbreak situation, a ring vaccination strategy for the high-risk group is more appropriate than the mass population vaccination with smallpox vaccines. Therefore, identifying the proper target group by available vaccines based on the risk and benefit analysis is a key issue of the vaccination program. In addition, the target group should be reviewed by the epidemiological situation of the jurisdiction along with the updated evidence of the monkeypox virus on transmission dynamics, severity, and fatality.

Preemptive Tecovirimat Use in an Active Duty Service Member Who Presented With Acute Myeloid Leukemia After Smallpox Vaccination.

Smallpox vaccine is contraindicated in immunosuppression due to increased risk for adverse reactions (eg, progressive vaccinia). We describe the first-ever use of tecovirimat as a preemptive vaccinia virus treatment strategy during induction chemotherapy in an active duty service member who presented with acute leukemia and inadvertent autoinoculation after smallpox vaccination.

Estimating the Size of the U.S. Population at Risk of Severe Adverse Events from Replicating Smallpox Vaccine.

OBJECTIVE: To quantify the population at risk of serious adverse reactions to replicating smallpox vaccine. DESIGN AND SAMPLE: Conditions known or suspected to carry risk were identified via Centers for Disease Control and Prevention planning documents, other federal publications, and peer-reviewed literature. Conditions identified were categorized as historically recognized risks or more recently recognized immunocompromised states that may pose risk. Major historical risk factors were as follows: eczema/atopic dermatitis, pregnancy, HIV, and primary immunodeficiency. More recently identified states were as follows: rheumatoid arthritis, inflammatory bowel disease, dialysis, bone marrow transplant recipients within 24 months post-transplant, solid-organ transplant recipients within 3 months post-transplant, age under 1 year, and systemic lupus erythematosus. MEASURES: The estimated prevalence or absolute number of affected individuals for each condition was ascertained from peer-reviewed studies, vital statistics, and registry databases. RESULTS: An estimated 48,121,280 to 50,028,045 individuals (15.2-15.8% of the U.S. population) are potentially contraindicated to replicating smallpox vaccine. This rises to 119,244,531 to 123,669,327 (37.4-38.8%) if household contacts are included. CONCLUSIONS: These figures are significant and larger than the only previously published study. Understanding this number allows for improved clinical utilization, equitable attention to the health needs of a vulnerable population, and strategic vaccine stockpiling.

Smallpox Vaccination of Laboratory Workers at US Variola Testing Sites.

To evaluate the need to revaccinate laboratory workers against smallpox, we assessed regular revaccination at the US Laboratory Response Network's variola testing sites by examining barriers to revaccination and the potential for persistence of immunity. Our data do not provide evidence to suggest prolonging the recommended interval for revaccination.