RBD conjugate vaccine with a built-in TLR1/2 agonist is highly immunogenic against SARS-CoV-2 and variants of concern.

The coronavirus 2019 (COVID-19) pandemic is causing serious impacts in the world, and safe and effective vaccines and medicines are the best methods to combat the disease. The receptor-binding domain (RBD) of the SARS-CoV-2 spike protein plays a key role in interacting with the angiotensin-converting enzyme 2 (ACE2) receptor, and is regarded as an important target of vaccines. Herein, we constructed the adjuvant-protein conjugate Pam3CSK4-RBD as a vaccine candidate, in which the N-terminal of the RBD was site-selectively oxidized by transamination and conjugated with the TLR1/2 agonist Pam3CSK4. This demonstrated that the conjugation of Pam3CSK4 significantly enhanced the anti-RBD antibody response and cellular response. In addition, sera from the Pam3CSK4-RBD immunized group efficiently inhibited the binding of the RBD to ACE2 and protected cells from SARS-CoV-2 and four variants of concern (alpha, beta, gamma and delta), indicating that this adjuvant strategy could be one of the effective means for protein vaccine development.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2020.

The Advisory Committee on Immunization Practices (ACIP) recommends that adolescents aged 11-12 years routinely receive tetanus, diphtheria, and acellular pertussis (Tdap); meningococcal conjugate (MenACWY); and human papillomavirus (HPV) vaccines. Catch-up vaccination is recommended for hepatitis B (HepB); hepatitis A (HepA); measles, mumps, and rubella (MMR); and varicella (VAR) vaccines for adolescents whose childhood vaccinations are not current. Adolescents are also recommended to receive a booster dose of MenACWY vaccine at age 16 years, and shared clinical decision-making is recommended for the serogroup B meningococcal vaccine (MenB) for persons aged 16-23 years (1). To estimate coverage with recommended vaccines, CDC analyzed data from the 2020 National Immunization Survey-Teen (NIS-Teen) for 20,163 adolescents aged 13-17 years.* Coverage with ≥1 dose of HPV vaccine increased from 71.5% in 2019 to 75.1% in 2020. The percentage of adolescents who were up to date† with HPV vaccination (HPV UTD) increased from 54.2% in 2019 to 58.6% in 2020. Coverage with ≥1 dose of Tdap, ≥1 dose (and among adolescents aged 17 years, ≥2 doses) of MenACWY remained similar to coverage in 2019 (90.1%, 89.3%, and 54.4% respectively). Coverage increased for ≥2 doses of HepA among adolescents aged 13-17 years and ≥1 dose of MenB among adolescents aged 17 years. Adolescents living below the federal poverty level§ had higher HPV vaccination coverage than adolescents living at or above the poverty level. Adolescents living outside a metropolitan statistical area (MSA)¶ had lower coverage with ≥1 MenACWY and ≥1 HPV dose, and a lower proportion being HPV UTD than adolescents in MSA principal cities. In 2020, the COVID-19 pandemic disrupted routine immunization services. Results from the 2020 NIS-Teen reflect adolescent vaccination coverage before the COVID-19 pandemic. The 2020 NIS-Teen data could be used to assess the impact of the COVID-19 pandemic on catch-up vaccination but not on routine adolescent vaccination because adolescents included in the survey were aged ≥13 years, past the age when most routine adolescent vaccines are recommended, and most vaccinations occurred before March 2020. Continued efforts to reach adolescents whose routine medical care has been affected by the COVID-19 pandemic are necessary to protect persons and communities from vaccine-preventable diseases and outbreaks.

SARS-CoV-2 RBD-Tetanus Toxoid Conjugate Vaccine Induces a Strong Neutralizing Immunity in Preclinical Studies.

Controlling the global COVID-19 pandemic depends, among other measures, on developing preventive vaccines at an unprecedented pace. Vaccines approved for use and those in development intend to elicit neutralizing antibodies to block viral sites binding to the host's cellular receptors. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response to this domain is an important outcome of immunization and correlates well with viral neutralization. Here, we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid (TT) induce a potent immune response in laboratory animals. Some advantages of immunization with RBD-TT conjugates include a predominant IgG immune response due to affinity maturation and long-term specific B-memory cells. These result demonstrate the potential of the conjugate COVID-19 vaccine candidates and enable their advance to clinical evaluation under the name SOBERANA02, paving the way for other antiviral conjugate vaccines.

National, Regional, State, and Selected Local Area Vaccination Coverage Among Adolescents Aged 13-17 Years - United States, 2019.

Three vaccines are recommended by the Advisory Committee on Immunization Practices (ACIP) for routine vaccination of adolescents aged 11-12 years to protect against 1) pertussis; 2) meningococcal disease caused by types A, C, W, and Y; and 3) human papillomavirus (HPV)-associated cancers (1). At age 16 years, a booster dose of quadrivalent meningococcal conjugate vaccine (MenACWY) is recommended. Persons aged 16-23 years can receive serogroup B meningococcal vaccine (MenB), if determined to be appropriate through shared clinical decision-making. CDC analyzed data from the 2019 National Immunization Survey-Teen (NIS-Teen) to estimate vaccination coverage among adolescents aged 13-17 years in the United States.* Coverage with ≥1 dose of HPV vaccine increased from 68.1% in 2018 to 71.5% in 2019, and the percentage of adolescents who were up to date† with the HPV vaccination series (HPV UTD) increased from 51.1% in 2018 to 54.2% in 2019. Both HPV vaccination coverage measures improved among females and males. An increase in adolescent coverage with ≥1 dose of MenACWY (from 86.6% in 2018 to 88.9% in 2019) also was observed. Among adolescents aged 17 years, 53.7% received the booster dose of MenACWY in 2019, not statistically different from 50.8% in 2018; 21.8% received ≥1 dose of MenB, a 4.6 percentage point increase from 17.2% in 2018. Among adolescents living at or above the poverty level,§ those living outside a metropolitan statistical area (MSA)¶ had lower coverage with ≥1 dose of MenACWY and with ≥1 HPV vaccine dose, and a lower percentage were HPV UTD, compared with those living in MSA principal cities. In early 2020, the coronavirus disease 2019 (COVID-19) pandemic changed the way health care providers operate and provide routine and essential services. An examination of Vaccines for Children (VFC) provider ordering data showed that vaccine orders for HPV vaccine; tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap); and MenACWY decreased in mid-March when COVID-19 was declared a national emergency (Supplementary Figure 1, https://stacks.cdc.gov/view/cdc/91795). Ensuring that routine immunization services for adolescents are maintained or reinitiated is essential to continuing progress in protecting persons and communities from vaccine-preventable diseases and outbreaks.