Together, this work shows that durable and robust GC-Tfh responses are key architects of high-quality antibody responses. They lead B cells toward their best performance.

Understanding how to sustain and shape these networks offers a path toward more effective and enduring vaccines.

We even detected same Tfh clones participating in different lymph nodes, suggesting a connected GC network.

Strong and functional GC-Tfh responses were associated with better antibodies, both in magnitude and quality. This suggests that effective vaccines can enhance Tfh responses that recruit and guide a broader B cell repertoire, ultimately driving antibody maturation toward neutralizing capability.

We found that vaccine-specific Tfh cells expand early and remain active for months, showing no signs of exhaustion.

Tracking Tfh clones across weeks showed not only that the same clones can persist, but also how these different Tfh subsets are interconnected.

We identified distinct subsets of GC-Tfh cells, including populations rich in IL-21 and IL-4, and with signatures of recent TCR engagement. We also spotted proliferating Tfh, Tfr, and IL10⁺ Tfh cells among others.

In our latest study in @cp-immunity.bsky.social, we followed dynamics of vaccine-specific Tfh cells for 60+ weeks after immunization.
authors.elsevier.com/a/1m3mV3qNrU...
We captured >500,000 CD4 T cells including >36,000 vaccine-specific Tfh by scRNAseq, giving an unprecedented longitudinal detail.

With the Schief lab we’ve shown that individual germline targeting immunogens can effectively prime bnAb-class responses in primates. The bnAb studies this work was based on:
* www.science.org/doi/full/10...., * www.nature.com/articles/s41..., * www.science.org/doi/10.1126/...

This work was made possible by continuous funding from the NIH over the past 10+ years. These HIV vaccine development studies take extensive coordination between labs.

This project was led by Harry Sutton in the lab in collaboration Schief lab @scripps.edu
A back-to-back paper by the fantastic Batista lab shows similar outcomes in mouse models, with the added advantage of showing success with mRNA vaccines.
www.science.org/doi/10.1126/...

No study had previously reported even a single detectable event of two bnAb lineages targeting distinct epitopes in vaccinated humans or outbred animals.

These findings demonstrate that multi-target GT vaccination is feasible, an important step toward an effective and practical HIV vaccine.

We isolated a total of 13 BG18-class (V3/glycan), 84 PCT64-class (Apex), and 134 10E8-class (MPER) unique clonal lineages from primates that received a triple combination GT immunization regimen. To our knowledge, this is the first report of its kind.

An effective HIV vaccine will likely need to elicit multiple bnAb classes simultaneously. In this study, we systematically tested whether different combinations of three HIV GT immunogens could prime bnAb-class responses. Turns out, the immune system can handle multitasking just fine.

1/ David Baltimore passed away this weekend. He was one of the greatest biologists of the past 100 years. He made extraordinary contributions to immunology, cancer, molecular biology, virology, HIV, biochemistry, genetics, and genetic engineering. He won the Nobel prize in Medicine at age 37.

Vaccine-specific cells in the upper airways of FluMist recipients showed recent activation (CD27+CD21-). No such activation was seen in the blood following FluMist, or in the upper airway following intramuscular vaccination, suggesting a local origin of the upper airway B cell responses.

Flumist essentially does not induce circulating antibodies in adults. But in the current study, we demonstrate substantial upper airway memory B cells in individuals who received the FluMist vaccine.

One key observation was that we could achieve consistent priming of rare B cells with a single bolus immunization using our preferred adjuvant, SMNP. This is a very encouraging sign for the related ongoing human clinical trials.

Under these extremely challenging vaccine conditions, we found that vaccine delivery strategy and adjuvant selection affect the recruitment and expansion of rare broadly neutralizing antibody-precursor B cells. We were impressed to see multiple rare clones recruited per animal.

…we have made use of a germline-targeting HIV vaccine immunogen selective for extraordinarily rare broadly neutralizing antibody-precursor B cells (rarer than 1 cell in 200,000,000) in a nontransgenic animal model.