Monkeypox is a zoonotic disease that was once endemic in west and central Africa caused by monkeypox virus. However, cases recently have been confirmed in many nonendemic countries outside of Africa. WHO declared the ongoing monkeypox outbreak to be a public health emergency of international concern on July 23, 2022, in the context of the COVID-19 pandemic. The rapidly increasing number of confirmed cases could pose a threat to the international community. Here, we review the epidemiology of monkeypox, monkeypox virus reservoirs, novel transmission patterns, mutations and mechanisms of viral infection, clinical characteristics, laboratory diagnosis and treatment measures. In addition, strategies for the prevention, such as vaccination of smallpox vaccine, is also included. Current epidemiological data indicate that high frequency of human-to-human transmission could lead to further outbreaks, especially among men who have sex with men. The development of antiviral drugs and vaccines against monkeypox virus is urgently needed, despite some therapeutic effects of currently used drugs in the clinic. We provide useful information to improve the understanding of monkeypox virus and give guidance for the government and relative agency to prevent and control the further spread of monkeypox virus. 

/pdf/monkeypox-epidemiology-pathogenesis-treatment-and-prevention-2y7yzkvx.pdf

Monkeypox: epidemiology, pathogenesis, treatment and prevention

Monkeypox has been declared a public health emergency by the World Health Organization. There is an urgent need for efficient and safe vaccines against the monkeypox virus (MPXV) in response to the rapidly spreading monkeypox epidemic. In the age of COVID-19, mRNA vaccines have been highly successful and emerged as platforms enabling rapid development and large-scale preparation. Here, we develop two MPXV quadrivalent mRNA vaccines, named mRNA-A-LNP and mRNA-B-LNP, based on two intracellular mature virus specific proteins (A29L and M1R) and two extracellular enveloped virus specific proteins (A35R and B6R). By administering mRNA-A-LNP and mRNA-B-LNP intramuscularly twice, mice induce MPXV specific IgG antibodies and potent vaccinia virus (VACV) specific neutralizing antibodies. Further, it elicits efficient MPXV specific Th-1 biased cellular immunity, as well as durable effector memory T and germinal center B cell responses in mice. In addition, two doses of mRNA-A-LNP and mRNA-B-LNP are protective against the VACV challenge in mice. And, the passive transfer of sera from mRNA-A-LNP and mRNA-B-LNP-immunized mice protects nude mice against the VACV challenge. Overall, our results demonstrate that mRNA-A-LNP and mRNA-B-LNP appear to be safe and effective vaccine candidates against monkeypox epidemics, as well as against outbreaks caused by other orthopoxviruses, including the smallpox virus. 

/pdf/monkeypox-virus-quadrivalent-mrna-vaccine-induces-immune-2ydinw4h.pdf

Monkeypox virus quadrivalent mRNA vaccine induces immune response and protects against vaccinia virus

This report compiles and summarizes all published recommendations from CDC's Advisory Committee on Immunization Practices (ACIP) for use of pneumococcal vaccines in adults aged ≥19 years in the United States.This report also includes updated and new clinical guidance for implementation from CDC.Before 2021, ACIP recommended 23-valent pneumococcal polysaccharide vaccine (PPSV23) alone (up to 2 doses), or both a single dose of 13-valent pneumococcal conjugate vaccine (PCV13) in combination with 1-3 doses of PPSV23 in series (PCV13 followed by PPSV23), for use in U.S. adults depending on age and underlying risk for pneumococcal disease.In 2021, two new pneumococcal conjugate vaccines (PCVs), a , were licensed for use in U.S. adults aged ≥18 years by the Food and Drug Administration.ACIP recommendations specify the use of either PCV20 alone or PCV15 in series with PPSV23 for all adults aged ≥65 years and for adults aged 19-64 years with certain underlying medical conditions or other risk factors who have not received a PCV or whose vaccination history is unknown.In addition, ACIP recommends use of either a single dose of PCV20 or ≥1 dose of PPSV23 for adults who have started their pneumococcal vaccine series with PCV13 but have not received all recommended PPSV23 doses.Shared clinical decision-making is recommended regarding use of a supplemental PCV20 dose for adults aged ≥65 years who have completed their recommended vaccine series with both PCV13 and PPSV23.Updated and new clinical guidance for implementation from CDC includes the recommendation for use of PCV15 or PCV20 for adults who have received PPSV23 but have not received any PCV dose.The report also includes clinical guidance for adults who have received 7-valent PCV (PCV7) only and adults who are hematopoietic stem cell transplant recipients.US Department of Health and Human Services/Centers for Disease Control and Prevention leak, or a cochlear implant (11).In 2014, ACIP recommended routine use of PCV13 in series with PPSV23 for all adults aged ≥65 years (12).This recommendation was supported by a large, randomized controlled trial (RCT) among pneumococcal vaccine-naïve, community-dwelling adults aged ≥65 years in the Netherlands that demonstrated efficacy of PCV13 against noninvasive pneumococcal pneumonia (13).In June 2019 ACIP voted to no longer routinely recommend PCV13 for all adults aged ≥65 years and, instead, to recommend PCV13 on the basis of shared clinical decision-making for adults aged ≥65 years who do not have an immunocompromising condition, a CSF leak, or a cochlear implant ( 14).The rationale for this decision was based on additional years of data that found minimal changes in the incidence of pneumococcal disease preventable by PCV13 among adults after the PCV13 recommendation for all adults aged ≥65 years was implemented and on the historically low levels of PCV13-type disease attributed to the indirect effects of pediatric PCV13 use.Although anatomic or functional asplenia, chronic renal failure, and nephrotic syndrome might not be considered immunocompromising ( 15), these conditions are included under immunocompromising conditions for pneumococcal vaccine recommendations because of the similarities in the vaccine recommendations.* Serotypes 15B and 15C are identified together as 15B/15C in the SSUAD test used in this study.$217,000 $93,000-$182,000 ¶ ¶ Abbreviations: IPD = invasive pneumococcal disease; NBPP = nonbacteremic pneumococcal pneumonia; PCV = pneumococcal conjugate vaccine; PCV13 = 13-valent pneumococcal conjugate vaccine; PCV15 = 15-valent pneumococcal conjugate vaccine; PCV20 = 20-valent pneumococcal conjugate vaccine; PPSV23 = 23-valent pneumococcal polysaccharide vaccine; QALY = quality-adjusted life-year; USD = U.S. dollars; VE = vaccine effectiveness.* In any scenario, the Tulane-CDC and Merck models start with a single-aged cohort of individuals, not a full population composed of many different ages.For this reason, these models have one specific starting age.For example, a cohort aged 70 years might be used to represent and estimate values in the group aged ≥65 years.† The Pfizer model base case used a multicohort model; however, single cohort results were provided in a scenario.§ The Tulane-CDC model includes one societal perspective component (i.e., travel cost added to the cost of vaccine administration).The Merck model provided a scenario using the societal perspective that was similar to the Tulane-CDC model.¶ The Tulane-CDC and Pfizer models included scenarios where no herd effects from pediatric vaccinations occurred.** The Tulane-CDC model varied PPSV23 VE against NBPP across two risk groups (adults with or without immunocompromising conditions).The Merck model varied PPSV23 VE against NBPP across three risk groups (low risk, at risk, and high risk).† † The Tulane-CDC and Merck models varied inpatient NBPP case-fatality ratios by age.The Pfizer model varied inpatient NBPP case-fatality ratios by age and risk group.§ § Original report was in 2021 USD, multiplied by 1.10 to adjust to 2022 USD.¶ ¶ The Merck model did not report a value for the comparison.The incremental value was calculated by the CDC team.*** Original report was in 2020 USD, multiplied by 1.15 to adjust to 2022 USD.ranged from $87,000 (Pfizer model: PCV20 administered 7 years after the PCV13 dose) to $611,000 (Tulane-CDC model: PCV20 administered to adults aged 66 years with an immunocompromising condition 1 year after the PCV13 dose).The Merck model did not report a value for this comparison.However, on the basis of calculations by the CDC review team, the Merck model estimated values that would be between the Pfizer and Tulane-CDC model estimates. 

pdf/pneumococcal-vaccine-for-adults-aged-19-years-38oagqjwsb.pdf

Pneumococcal Vaccine for Adults Aged ≥19 Years: Recommendations of the Advisory Committee on Immunization Practices, United States, 2023

At its October 2022 meeting, the Advisory Committee on Immunization Practices* (ACIP) approved the Recommended Child and Adolescent Immunization Schedule for Ages 18 Years or Younger, United States, 2023. The 2023 child and adolescent immunization schedule, available on the CDC immunization schedule website (https://www.cdc.gov/vaccines/schedules), summarizes ACIP recommendations, including several changes from the 2022 immunization schedule† on the cover page, tables, notes, and appendix. Health care providers are advised to use the tables, notes, and appendix together to determine recommended vaccinations for patient populations. This immunization schedule is recommended by ACIP (https://www.cdc.gov/vaccines/acip) and approved by CDC (https://www.cdc.gov), the American Academy of Pediatrics (https://www.aap.org), the American Academy of Family Physicians (https://www.aafp.org), the American College of Obstetricians and Gynecologists (http://www.acog.org), the American College of Nurse-Midwives (https://www.midwife.org), the American Academy of Physician Associates (https://www.aapa.org), and the National Association of Pediatric Nurse Practitioners (https://www.napnap.org).

https://www.cdc.gov/mmwr/volumes/72/wr/pdfs/mm7206a1-H.pdf

Advisory Committee on Immunization Practices Recommended Immunization Schedule for Children and Adolescents Aged 18 Years or Younger — United States, 2023

Introduction In early to mid-2022, an unexpected outbreak of Monkeypox virus infections occurred outside the African endemic regions. Vaccines originally developed in the past to protect against smallpox are one of the available countermeasures to prevent and protect against Orthopoxvirus infections. To date, there are few studies on the cross-reactivity of neutralizing antibodies elicited by previous vaccinia virus-based vaccination and/or Monkeypox virus infection. The aim of this study was to evaluate a possible approach to performing Monkeypox and vaccinia live-virus microneutralization assays in which the read-out is based on the production of cytopathic effect in the cell monolayer. Methods Given the complexity of Orthopoxviruses, the microneutralization assay was performed in such a way as to uncover a potential role of complement, with and without the addition of an external source of Baby Rabbit Complement. A set of human serum samples from individuals who had been naturally infected with Monkeypox virus and individuals who may have and not have undergone vaccinia virus vaccinations, was used to evaluate the performance, sensitivity, and specificity of the assay. Results and conclusions The results of the present study confirm the presence and cross-reactivity of antibodies elicited by vaccinia-based vaccines, which proved able to neutralize the Monkeypox virus in the presence of an external source of complement.

/pdf/evaluation-of-monkeypox-and-vaccinia-virus-neutralizing-26nxcmn0.pdf

Evaluation of Monkeypox- and Vaccinia virus-neutralizing antibodies in human serum samples after vaccination and natural infection

The 13-valent pneumococcal conjugate vaccine (PCV13 [Prevnar 13, Wyeth Pharmaceuticals, Inc, a subsidiary of Pfizer, Inc]) and the 23-valent pneumococcal polysaccharide vaccine (PPSV23 [Merck Sharp & Dohme LLC]) have been recommended for U.S. children, and the recommendations vary by age group and risk group (1,2). In 2021, 15-valent pneumococcal conjugate vaccine (PCV15 [Vaxneuvance, Merck Sharp & Dohme LLC]) was licensed for use in adults aged ≥18 years (3). On June 17, 2022, the Food and Drug Administration (FDA) approved an expanded usage for PCV15 to include persons aged 6 weeks-17 years, based on studies that compared antibody responses to PCV15 with those to PCV13 (4). PCV15 contains serotypes 22F and 33F (in addition to the PCV13 serotypes) conjugated to CRM197 (genetically detoxified diphtheria toxin). On June 22, 2022, CDC's Advisory Committee on Immunization Practices (ACIP) recommended use of PCV15 as an option for pneumococcal conjugate vaccination of persons aged <19 years according to currently recommended PCV13 dosing and schedules (1,2). ACIP employed the Evidence to Recommendation (EtR) Framework,* using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE)† approach to guide its deliberations regarding use of these vaccines. Risk-based recommendations on use of PPSV23 for persons aged 2-18 years with certain underlying medical conditions§ that increase the risk for pneumococcal disease have not changed.

/pdf/use-of-15-valent-pneumococcal-conjugate-vaccine-among-u-s-uebgnr3l.pdf

Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022

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Use of 15-Valent Pneumococcal Conjugate Vaccine Among U.S. Children: Updated Recommendations of the Advisory Committee on Immunization Practices — United States, 2022