Vaccines and Adjuvants Group

Objective

Examine the role of T cells in shaping and sustaining humoral immunity to SARS-CoV-2 and identify immune factors associated with durable antibody responses.

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Current literature informs us that bivalent vaccines will generate a broader serum neutralizing antibody response to multiple SARS-CoV-2 variants, but studies on how this breadth relates to the memory B cell (MBC) and T cell responses are sparse. This study compared breadth of neutralising antibody, and memory B and T cell responses to monovalent or a bivalent ancestral/Omicron BA.1 COVID-19 booster vaccine.

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Herpes zoster (HZ) is increasingly common in the aging and is experienced by approximately one in three people in their lifetime. It is also relatively common in immune-compromised people. Acute HZ causes severe pain, reduced quality of life and severe complications, including prolonged pain, or postherpetic neuralgia (PHN), and ocular zoster, which may rarely progress to blindness. In severely immune-compromised people disseminated zoster may affect the brain and liver. A second-generation vaccine, the Recombinant Zoster Vaccine, consisting of recombinant viral glycoprotein E and the Adjuvant System 01 (AS01B), now offers >90% efficacy against HZ and associated complications in immune-competent people. Efficacy persists above 80% for 11 years. In severely immune-compromised patients, the vaccine is safe with efficacy and/or immunogenicity of 68–87%. There is also excellent immunogenicity for those on JAK inhibitors and corticosteroid therapy. The vaccine offers a paradigm for successful and durable immunization in the aging and immune-compromised.

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Vaccine adjuvants are thought to work by stimulating innate immunity in the draining lymph node (LN), although this has not been proven in humans. To bridge the data obtained in animals to humans, we have developed an in situ human LN explant model to investigate how adjuvants initiate immunity. Slices of explanted LNs were exposed to vaccine adjuvants and revealed responses that were not detectable in LN cell suspensions. We used this model to compare the liposome-based AS01 with its components, monophosphoryl lipid A (MPL) and QS-21, and TLR ligands. Liposomes were predominantly taken up by subcapsular sinus–lining macrophages, monocytes, and DCs. AS01 induced DC maturation and a strong proinflammatory cytokine response in intact LN slices but not in dissociated cell cultures, in contrast to R848. This suggests that the onset of the immune response to AS01 required a coordinated activation of LN cells in time and space. Consistent with the robust immune response observed in older adults with AS01-adjuvanted vaccines, the AS01 response in human LNs was independent of age, unlike the response to R848. This human LN explant model is a valuable tool for studying the mechanism of action of adjuvants in humans and for screening new formulations to streamline vaccine development.

Vicki V. Stylianou, … , Kerrie J. Sandgren, Anthony L. Cunningham
J Clin Invest. 2024;134(22):e174144 https://doi.org/10.1172/JCI174144

Cunningham AL, Sandgren KJ, Truong, NR. Advances in understanding the mechanism of action of adult vaccines. J Clin Invest. 2023;133(23):e175378.

Duette G, Lee E, Martins Costa Gomes G, Tungatt K, Doyle CM, Stylianou VV, Lee A, Taylor J, Khanna R, Sandgren KJ*, Cunningham AL*, Palmer SP* (*equal last authors). Highly networked SARS-CoV-2 peptides elicit T cell responses with enhanced specificity. ImmunoHorizons. 2023. Jun 1;7(6):508-527.