Novel Combination Vaccine Adjuvant for Older Adults Studied in the Immunosenescent Mouse Model
E. V. Vassilieva
Emory University School of Medicine, Atlanta, GA
Discuss vaccination needs specific to the aged population and critically evaluate data obtained in preclinical research using an aged mouse model
The yearly influenza vaccination rate of the US population over 65 years old is the highest among adults, and yet over 80% of influenza-related deaths occur in this age group , demonstrating the lack of effectiveness of current vaccines. This presentation will address vaccination challenges faced by the aged population and describe progress in identifying novel influenza vaccine adjuvants for this target group. We recently demonstrated that the combination of an activator of the stimulator of interferon genes (STING) pathway, 2’3 cyclic guanosine monophosphate–adenosine monophosphate (cGAMP), and a saponin-based adjuvant, Quil-A, was highly effective in boosting protective immunity of influenza vaccine in an aged mouse model.  A single dose of A/California 07/09 H1N1 influenza vaccine adjuvanted with this combination protected mice against viral challenge with the matching influenza virus better than current options for people over 65 years old (vaccine formulated with squalene-based adjuvant or high-dose antigen formulation). Activation of STING enhances development of the immune response to vaccine antigens , and we confirmed that saponin facilitated access of cGAMP to the intracellular STING receptor.
1. Rolfes MA, Flannery B, Chung JR, et al. Effects of influenza vaccination in the United States dring the 2017-2018 influenza season. Clin Infect Dis. 2019;69(11):1845-1853.
2. Vassilieva EV, Taylor DW, Compans RW. Combination of STING pathway agonist with saponin is an effective adjuvant in immunosenescent mice. Front Immunol. 2019;10:3006.
3. Dubensky TW, Jr., Kanne DB, Leong ML. Rationale, progress and development of vaccines utilizing STING-activating cyclic dinucleotide adjuvants. Ther Adv Vaccines. 2013;1(4):131-143.
Using Enhanced Influenza Vaccines in the Immunocompromised Population
C. N. Kotton
Massachusetts General Hospital, Boston, MA
- Review the response to influenza vaccines in the setting of immunosuppression
- Discuss approaches to enhancing response to vaccination in this population
- Discuss considerations for possible adverse events from vaccination
Immunocompromised hosts are more vulnerable to both opportunistic and common infections, and are more likely to experience significant morbidity and mortality from such infections. Vaccination is one of the most effective methods of infection prevention. Immunocompromised hosts are less likely to develop robust immune responses after immunization, both with respect to the depth and duration of immunity. Various approaches to optimizing protection from vaccines have been considered and evaluated, including use of higher dose vaccine and/or multiple doses, optimization of timing of vaccination during periods of less immunosuppression, and varied administration approaches (e.g., intradermal); these will be reviewed. Although vaccination is general considered safe, there may be adverse events to consider in this medically complex population.
1. Danziger‐Isakov, L, Kumar, D; On Behalf of The AST ID Community of Practice. Vaccination of solid organ transplant candidates and recipients: Guidelines from the American society of transplantation infectious diseases community of practice. Clin Transplant. 2019; 33:e13563. doi.org/10.1111/ctr.13563.
2. Arnaud G L’huillier, Victor H Ferreira, Cedric Hirzel, Yoichiro Natori, Jaclyn Slomovic, Terrance Ku, Katja Hoschler, Matthew Ierullo, Nazia Selzner, Jeffrey Schiff, Lianne G Singer, Atul Humar, Deepali Kumar, Cell-Mediated Immune Responses After Influenza Vaccination of Solid Organ Transplant Recipients: Secondary Outcomes Analyses of a Randomized Controlled Trial, The Journal of Infectious Diseases, Volume 221, Issue 1, 1 January 2020, Pages 53–62. doi.org/10.1093/infdis/jiz471.
3. Yoichiro Natori, Mika Shiotsuka, Jaclyn Slomovic, Katja Hoschler, Victor Ferreira, Peter Ashton, Coleman Rotstein, Les Lilly, Jeffrey Schiff, Lianne Singer, Atul Humar, Deepali Kumar, A Double-Blind, Randomized Trial of High-Dose vs Standard-Dose Influenza Vaccine in Adult Solid-Organ Transplant Recipients, Clinical Infectious Diseases, Volume 66, Issue 11, 1 June 2018, Pages 1698–1704. doi.org/10.1093/cid/cix1082.
Respiratory Syncytial Virus Vaccines in Pregnant Women
J. A. Englund
University of Washington, Seattle, WA
- Identify the epidemiological trends and clinical disease associated with respiratory syncytial virus (RSV) during pregnancy and in infants
- Characterize mechanisms of maternal antibody transfer during pregnancy to infants
- Recognize new RSV vaccines undergoing early clinical studies
- Describe results of the first placebo-controlled maternal RSV immunization study
- Describe potential mechanisms of maternal antibody transfer and possible vaccines that may protect infants from RSV disease
Immunization of the pregnant woman has the potential to help protect the woman against infection as well as protect her fetus and the infant after birth. This “multiple” benefit is related to the mother not exposing the infant directly to an infection, as well as the active transport of maternal antibodies across the placenta to the fetus which then persists after birth. The epidemiology of respiratory syncytial virus (RSV) in infants demonstrates the high risk of serious disease during the first few months of life, although serious disease in pregnant women appears to be much less common. Vaccines are being developed and tested to induce potentially protective immunity to RSV infection in infants, children, adults, and older adults, with many vaccine strategies emphasizing the pre-fusion protein of RSV. RSV vaccines that will be used in pregnant women need to be safe and immunogenic, and likely will be protein-based vaccines that do not utilize novel adjuvants. Potential maternal vaccines aimed at preventing respiratory syncytial virus will be discussed in this presentation, and preliminary results of the first placebo-controlled RSV maternal immunization vaccine trial presented.
1. Chu HY, Tielsch J, Katz J, Magaret AS, et al. Transplacental transfer of maternal respiratory syncytial virus (RSV) antibody and protection against RSV disease in infants in rural Nepal. J Clin Virol. 2017 Oct;95:90-95.
2. Chu HY, Englund JA. Maternal immunization. Birth Defects Res 2017; Mar 15 109:379-386.
3. Maertens K, Oriie MRP, Van Damme P, Leuridan E. Vaccination during pregnancy: current and possible future recommendations. Eur J Pediatr 2020 Jan 7. doi: 10.1007/s00431-019-03563-w. [Epub ahead of print].
4. Munoz FM, Swamy GK, Hickma SP, et al. Safety and Immunogenicity of a Respiratory Syncytial Virus Fusion (F) Protein Nanoparticle Vaccine in Healthy Third-Trimester Pregnant Women and Their Infants. J Infect Dis. 2019 Oct 22;220:1802–1815.
5. Schwartz TF, McPhee RA, Launay O, Leruoux-Roels G, et al. immunogenicity and safety of 3 formulations of a RSV candidate vaccine in non-pregnant women: A phase 2 randomized trial. J Infect Dis 2019;220:1816-1825.