Polyfunctional T Cell and Neutralizing Antibody Responses to ACAM2000TM Smallpox Vaccine Immunization in Primary-Vaccinated Individuals

Smallpox eradication was successful via prophylactic administration of live attenuated vaccinia virus. As a result of the discontinuation of the smallpox immunization program, many individuals are now susceptible to smallpox virus infection should it be used as a biological weapon. Presently, only individuals at high risk for exposure are required to receive smallpox vaccine, such as laboratory personnel that handle variola/vaccinia virus. This study endeavored to investigate a one-year period of vaccinia virus-specific T cell responses using polychromatic flow cytometry and neutralizing (Nt) antibody responses using plaque reduction neutralization test (PRNT) in individuals receiving primary immunization (n = 5) with ACAM2000TM smallpox vaccine. Functional and phenotypic profiles of vaccinia virus-specific T cell responses were characterized. Each single functional measurement {CD107a/b expression, production of interferon g (IFN-g), macrophage inflammatory protein 1b (MIP-1b), interleukin 2 (IL-2), and tumor necrosis factor a (TNF-a)} demonstrated that vaccinia virus-specific CD8+ T cells were functional at least one time point after vaccination (p ≤ 0.05). However, vaccinia virus-specific CD4+ T cells were functional only for MIP-1b production (p ≤ 0.05). Vaccinia virus-specific CD8+ T cells induced in these individuals showed increased polyfunctionality in at least 2 phenotypes relative to pre-vaccination (p ≤ 0.05). Although only three of five individuals (60%) showed positive Nt antibody (titer ≥ 20) at first month after vaccination, all five individuals (100%) demonstrated Nt antibody at 2 months, post-immunization. Interestingly, all vaccinees could retain the Nt antibody for 6 months after primary vaccination. In conclusion, ACAM2000TM smallpox vaccine induced both polyfunctional T cell-and Nt antibody-responses in primary immunized individuals.

Inequity in the global distribution of monkeypox vaccines

Monkeypox(mpox)has been a public health emergency of international concern that emerged in mid-2022 and has spread to 110 countries.The clinical findings of the disease vary according to the seriousness of the cases.Although its case fatality risk has not been high,a significant percentage of patients require hospitalization.In this context,local initiatives were taken to extend the limited supply of vaccines against the disease;however,such measures have not been sufficient to contain the spread of cases and ensure an equitable distribution of health resources.As a result,endemic regions of low-income countries continue to have insufficient access to mpox vaccination.Despite this and considering the global scope of the disease,there is still little discussion in the literature about the difficulties in achieving adequate vaccination coverage rates for the target population of interest.In this article,we briefly discussed general aspects of the disease,including its surveillance,the current global context of challenges for mpox vaccination,and issues on global allocation of health resources as well as proposed related recommendations.

Monkeypox: A Viral Zoonotic Disease of Rising Global Concern

Monkeypox(mpox)is a rare viral zoonotic disease,endemic to Central and West Africa,caused by the monkeypox virus,an orthopoxvirus similar to the variola virus(smallpox).Although sporadic travel-associated cases have historically occurred outside Africa,in May 2022,mpox began spreading globally in multiple nonendemic countries across several continents.In 2024,there has been an increase in globally reported confirmed cases of mpox and deaths from mpox,making it a public health emergency of international concern.The reasons for the unusual global spread are under investigation but likely relate to increased travel and waning population immunity to orthopoxviruses.Transmission now appears to be mainly through close,intimate contact,especially among men who have sex with men.Mpox is usually a self-limited disease.Although limited approved antiviral treatments are available,such as tecovirimat,which the European Medicines Agency approved in January 2022 for the treatment of mpox,their widespread availability and effectiveness in the current outbreak remain to be investigated.Public health control measures include surveillance,case identification/isolation,contact tracing,and targeted vaccination of contacts at high risk of exposure.However,challenges remain in curtailing the current unprecedented outbreak.Critical knowledge gaps include animal reservoir(s)responsible for initial spillover events,viral mutations that may enhance transmissibility,optimal diagnostics for noninvasive specimens,effective antiviral therapies,next-generation vaccines providing longer-term immunity,and building global capacity for outbreak response.This review summarizes the current literature on mpox virology,epidemiology,pathogenesis,clinical manifestations,diagnostics,treatment,prevention,and public health control measures.Ongoing investigation and research are needed to better understand mpox’s evolving epidemiology,pathogenicity,transmissibility,and ecology to guide strategies for containing the outbreak and preventing future global emergence.

Monkeypox virus:a re-emergent threat to humans

Human monkeypox(MPX)is a rare zoonotic infection characterized by smallpox-like signs and symptoms.It is caused by monkeypox virus(MPXV),a double stranded DNA virus belonging to the genus Orthopoxvirus.MPX was first identified in 1970 and mostly prevailed in the rural rainforests of Central and West Africa in the past.Outside Africa,MPX was reported in the United Kingdom,the USA,Israel,and Singapore.In 2022,the resurgence of MPX in Europe and elsewhere posed a potential threat to humans.MPXV was transmitted by the animals-human or human-human pathway,and the symptoms of MPXV infection are similar to that of smallpox,but in a milder form and with lower mortality(1%–10%).Although the smallpox vaccination has been shown to provide 85%protection against MPXV infection,and two anti-smallpox virus drugs have been approved to treat MPXV,there are still no specific vaccines and drugs against MPXV infection.Therefore it is urgent to take active measures including the adoption of novel anti-MPXV strategies to control the spread of MPXV and prevent MPX epidemic.In this review,we summarize the biological features,epidemiology,pathogenicity,laboratory diagnosis,and prevention and treatment strategies on MPXV.This review provides the basic knowledge for prevention and control of future outbreaks of this emerging infection.