vaccines

Updated Evidence for Covid-19, RSV, and Influenza Vaccines for 2025–2026

Author/s: 
Michael S. Abers, Jake Scott, Harleen K. Marwah, Nicole C. McCann, Eric A. Meyerowitz, Aaron Richterman, Derek F. Fleming, Caitlin M. Dugdale

Background: Changes in the vaccine advisory process in the United States have disrupted immunization guidance, which reinforces the need for independent evidence review to inform decisions regarding immunization for respiratory viruses during the 2025-2026 season.

Methods: We conducted a systematic review of U.S.-licensed immunizations against coronavirus disease 2019 (Covid-19), respiratory syncytial virus (RSV), and influenza. We searched databases on PubMed/MEDLINE, Embase, and Web of Science for updates of the most recent review by the Advisory Committee on Immunization Practices (ACIP) Evidence-to-Recommendations for each disease, which was performed during the 2023-2024 period. Outcomes included vaccine efficacy and effectiveness against hospitalization, other clinical end points, and safety.

Results: Of 17,263 identified references, 511 studies met the inclusion criteria. Covid-19 mRNA vaccines against the XBB.1.5 subvariant had pooled vaccine effectiveness against hospitalization of 46% (95% confidence interval [CI], 34 to 55; from cohort studies) and 50% (95% CI, 43 to 57; from case-control studies) among adults and 37% (95% CI, 29 to 44) among immunocompromised adults. In a case-control study, vaccines against the KP.2 subvariant showed an effectiveness of 68% (95% CI, 42 to 82). Maternal RSV vaccination (for infant protection), nirsevimab for infants, and RSV vaccines in adults who were 60 years of age or older showed vaccine effectiveness of 68% or more against hospitalization. Influenza vaccination had a pooled vaccine effectiveness of 48% (95% CI, 39 to 55) in adults between the ages of 18 and 64 years and 67% (95% CI, 58 to 75) in children against hospitalization. Safety profiles were consistent with previous evaluations. The diagnosis of myocarditis associated with Covid-19 vaccines occurred at rates of 1.3 to 3.1 per 100,000 doses in male adolescents, with lower risk associated with longer dosing intervals. The RSVpreF vaccine was associated with 18.2 excess cases of Guillain-Barré syndrome per million doses in older adults; a significant association with preterm birth was not observed when the vaccine was administered at 32 to 36 weeks' gestation.

Conclusions: Ongoing peer-reviewed evidence supports the safety and effectiveness of immunizations against Covid-19, RSV, and influenza during the 2025-2026 season. (Funded by the Center for Infectious Disease Research and Policy and the Alumbra Innovations Foundation.).

Covid-19 Vaccines — Immunity, Variants, Boosters

Author/s: 
Barouch, D. H.

The coronavirus disease 2019 (Covid-19) pandemic has claimed an estimated 15 million lives, including more than 1 million lives in the United States alone. The rapid development of multiple Covid-19 vaccines has been a triumph of biomedical research, and billions of vaccine doses have been administered worldwide. Challenges facing the Covid-19 vaccine field include inequitable vaccine distribution, vaccine hesitancy, waning immunity, and the emergence of highly transmissible viral variants that partially escape antibodies. This review summarizes the current state of knowledge about immune responses to Covid-19 vaccines and the importance of both humoral and cellular immunity for durable protection against severe disease.

Allergic Reactions Including Anaphylaxis After Receipt of the First Dose of Pfizer-BioNTech COVID-19 Vaccine

Author/s: 
Shimabukuro, T., Nair, N.

On December 11, 2020, the US Food and Drug Administration (FDA) issued an Emergency Use Authorization (EUA) for the Pfizer-BioNTech coronavirus disease 2019 (COVID-19) vaccine, administered as 2 doses separated by 21 days.1 Shortly after, the Advisory Committee on Immunization Practices (ACIP) issued an interim recommendation for its use.2 Following implementation of vaccination, reports of anaphylaxis after the first dose of the Pfizer-BioNTech COVID-19 vaccine emerged.3 Anaphylaxis is a life-threatening allergic reaction that occurs rarely after vaccination, with onset typically within minutes to hours.4

Notifications and reports of suspected severe allergic reactions and anaphylaxis following vaccination were captured in the Vaccine Adverse Event Reporting System (VAERS), the national passive surveillance (spontaneous reporting) system for adverse events after immunization.5 Physicians at the US Centers for Disease Control and Prevention (CDC) evaluated these reports and applied Brighton Collaboration case definition criteria6 to classify case reports as anaphylaxis or not anaphylaxis. Nonallergic adverse events, mostly vasovagal or anxiety-related, were excluded from the analysis. Anaphylaxis and nonanaphylaxis allergic reaction cases with symptom onset occurring later than the day after vaccination were also excluded because of the difficulty in clearly attributing allergic reactions with delayed onset after vaccination. Because the Moderna COVID-19 vaccine was only available beginning December 21, 2020, this article focuses on the Pfizer-BioNTech COVID-19 vaccine.

During December 14 to 23, 2020, after administration of a reported 1 893 360 first doses of Pfizer-BioNTech COVID-19 vaccine (1 177 527 in women, 648 327 in men, and 67 506 with sex of recipient not reported),3 CDC identified 21 case reports submitted to VAERS that met Brighton Collaboration case definition criteria for anaphylaxis (Table), corresponding to an estimated rate of 11.1 cases per million doses administered. Four patients (19%) were hospitalized (including 3 in intensive care), and 17 (81%) were treated in an emergency department; 20 (95%) are known to have been discharged home or had recovered at the time of the report to VAERS. No deaths from anaphylaxis were reported.

Maintaining Safety with SARS-CoV-2 Vaccines

Author/s: 
Castells, Mariana C., Phillips, Elizabeth J.

To date, the development of mRNA vaccines for the prevention of infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been a success story, with no serious concerns identified in the ongoing phase 3 clinical trials.1 Minor local side effects such as pain, redness, and swelling have been observed more frequently with the vaccines than with placebo. Systemic symptoms such as fever, fatigue, headache, and muscle and joint pain have also been somewhat more common with the vaccines than with placebo, and most have occurred during the first 24 to 48 hours after vaccination.1 In the phase 1–3 clinical trials of the Pfizer–BioNTech and Moderna mRNA vaccines, potential participants with a history of an allergic reaction to any component of the vaccine were excluded. The Pfizer–BioNTech studies also excluded participants with a history of severe allergy associated with any vaccine (see the protocols of the two trials, available with the full text of the articles at NEJM.org, for full exclusion criteria).1,2 Hypersensitivity adverse events were equally represented in the placebo (normal saline) and vaccine groups in both trials.1

Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020

Author/s: 
Mbaeyi, Sarah A., Bozio, Catherine H., Duffy, Jonathan, Rubin, Lorry, Hariri, Susan, Stephens, David S., MacNeil, Jessica R.

This report compiles and summarizes all recommendations from CDC’s Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines.

ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk.

In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16–23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.

Meningococcal Vaccination: Recommendations of the Advisory Committee on Immunization Practices, United States, 2020

Author/s: 
Mbaeyi, Sarah A., Bozio, Catherine H., Duffy, Jonathan, Rubin, Lorry, Hariri, Susan, Stephens, David S., MacNeil, Jessica R.

This report compiles and summarizes all recommendations from CDC’s Advisory Committee on Immunization Practices (ACIP) for use of meningococcal vaccines in the United States. As a comprehensive summary and update of previously published recommendations, it replaces all previously published reports and policy notes. This report also contains new recommendations for administration of booster doses of serogroup B meningococcal (MenB) vaccine for persons at increased risk for serogroup B meningococcal disease. These guidelines will be updated as needed on the basis of availability of new data or licensure of new meningococcal vaccines.

ACIP recommends routine vaccination with a quadrivalent meningococcal conjugate vaccine (MenACWY) for adolescents aged 11 or 12 years, with a booster dose at age 16 years. ACIP also recommends routine vaccination with MenACWY for persons aged ≥2 months at increased risk for meningococcal disease caused by serogroups A, C, W, or Y, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor (e.g., eculizumab [Soliris] or ravulizumab [Ultomiris]); persons who have anatomic or functional asplenia; persons with human immunodeficiency virus infection; microbiologists routinely exposed to isolates of Neisseria meningitidis; persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroups A, C, W, or Y; persons who travel to or live in areas in which meningococcal disease is hyperendemic or epidemic; unvaccinated or incompletely vaccinated first-year college students living in residence halls; and military recruits. ACIP recommends MenACWY booster doses for previously vaccinated persons who become or remain at increased risk.

In addition, ACIP recommends routine use of MenB vaccine series among persons aged ≥10 years who are at increased risk for serogroup B meningococcal disease, including persons who have persistent complement component deficiencies; persons receiving a complement inhibitor; persons who have anatomic or functional asplenia; microbiologists who are routinely exposed to isolates of N. meningitidis; and persons identified to be at increased risk because of a meningococcal disease outbreak caused by serogroup B. ACIP recommends MenB booster doses for previously vaccinated persons who become or remain at increased risk. In addition, ACIP recommends a MenB series for adolescents and young adults aged 16–23 years on the basis of shared clinical decision-making to provide short-term protection against disease caused by most strains of serogroup B N. meningitidis.

Immunization Strategies to Span the Spectrum of Immunocompromised Adults

Author/s: 
Whitaker, JA

The Advisory Committee on Immunization Practices to the US Centers for Disease Control and Prevention provides annual recommendations for routine adult immunizations. Many recommendations consider patient factors such as age, medical conditions, and medications that increase an individual’s risk for infection with a vaccine-preventable disease. These factors, particularly those that lead to immunocompromise, may also alter the risk-benefit ratio for live vaccines, and/or lead to decreased vaccine immunogenicity and effectiveness. The provider may need to consider alternative vaccination strategies, including higher antigen dose vaccines, adjuvanted vaccines, avoidance of live vaccines, and careful timing of vaccination to optimize safety and effectiveness in immunocompromised populations. This thematic review discusses general principles regarding immunization of adults across the spectrum of immunocompromise, examines current guidelines and studies that support them, and outlines future research needs.

Routine Childhood Vaccines Given in the First 11 Months After Birth

Author/s: 
Jacobson, RM

The US Advisory Committee on Immunization Practices recommends that infants beginning at birth receive several vaccines directed against a variety of infectious diseases that currently pose threats of morbidity and mortality to infants and those around them, including the 3-dose hepatitis B (HepB) series. The first dose is due at birth. This series protects against maternal-infant transmission of the HepB virus and against exposure the rest of the infant's life. At age 2 months infants are to receive not only their second dose of HepB vaccine but also a series of vaccines directed against diphtheria, tetanus, pertussis, pneumococcus, rotavirus, poliovirus, and Haemophilus influenzae type b. At 4 months, infants are to repeat those vaccines except for the HepB vaccine. At age 6 months infants are to finish the HepB series and receive the third doses of the other vaccines received at 2 and 4 months except for the rotavirus vaccine, depending on the brand used. Also, starting at 6 months, depending on the time of year, infants are to begin a 2-dose series against influenza separated by 28 days. Each of these vaccines is due at a time when the vaccine works to protect against an immediate risk and to provide long-term protection. These vaccine-preventable diseases vary in terms of the nature of exposure, the form of the morbidity, the risk of mortality, and the ability of routine vaccination to prevent or ameliorate harm.

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