Vaccine additives can enhance immune flexibility -- Implications for flu
and SARS-CoV-2

Date:
July 16, 2020
Source:
Emory Health Sciences
Summary:
A vaccine additive known as an adjuvant can enhance responses to
a vaccine containing the exotic avian flu virus H5N1, so that both
rookie and veteran elements of the immune response are strengthened,
according to a new study.



FULL STORY ==========================================================================
A vaccine additive known as an adjuvant can enhance responses to a
vaccine containing the exotic avian flu virus H5N1, so that both rookie
and veteran elements of the immune response are strengthened, according
to results from an Emory Vaccine Center study.


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The findings have implications for the effort to develop vaccines against multiple strains of flu, as well as the current push for vaccines
against SARS- CoV-2. The Emory study was a test of what happens when
the body sees something new -- in contrast to seasonal flu vaccination,
which often re-activates the same memory B cells the immune system relied
upon in past years.

The study provides guidance on how adjuvants might become part of a
proposed "universal" flu vaccine, aimed at protecting people against
a wider variety of influenza strains. In addition, vaccine designers
are considering how to optimize immune responses against SARS-Cov-2,
which few had encountered before 2020.

The results were published online July 13 by Proceedings of the National Academy of Sciences.

"We saw that an adjuvant makes it possible to efficiently engage both
memory and naive B cells, expanding the repertoire of the antibody
immune response to influenza," says first author Ali Ellebedy, PhD,
who did the study while he was a postdoctoral fellow in Rafi Ahmed's
lab at Emory Vaccine Center.

"For a new pathogen like SARS-CoV-2, nobody has immunity," Ahmed
says. "So the important thing is to have the vaccine bring out good
responses from nai"ve B cells, whose frequency is low." "For universal
flu, the situation is more complicated. You want to bring out both the cross-reactive memory cells and the nai"ve strain-specific cells,"
adds Ahmed, whose lab is part of a NIH-funded consortium developing
flu vaccine candidates. "Looking ahead, adjuvants are going to be an
important element of universal flu vaccine research."


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The particular adjuvant studied in the paper is called AS03, whose
manufacturer GlaxoSmithKline is making it available for COVID-19 vaccine trials. The AS03 adjuvant could be relevant for extending the efficacy
of limited doses of protein or viral subunit-based vaccines, but less
so for newer mRNA-based vaccines, Ahmed says.

The Hope Clinic study recruited 50 healthy young adults, who were
(most likely) exposed to other flu viruses and vaccines earlier in their
lives. The H5N1 vaccine, with AS03, was approved by the FDA in 2013 and is
part of the national stockpile in case of pandemic flu. More information
about the AS03-adjuvanted flu vaccine is available from the FDA.

Emory researchers had previously observed that when the immune system encounters an unfamiliar flu virus, which occurred for many during the
2009 H1N1 pandemic, the antibodies produced are able to neutralize a
broader range of viruses. This came from the skew of the antibodies
toward the "stem" (or stalk) region of the viral hemagglutinin protein,
versus the "head." The stem region doesn't mutate and change as much as
the head from year to year.

A similar phenomenon occurred in the H5N1 study, because the head region
of the virus was unfamiliar, but the stem region was not. Without an
adjuvant, the immune response to a low dose of the H5N1 flu vaccine was
poor, the researchers found.

But with the adjuvant, immune responses changed markedly between the first
and second dose. A week after the first adjuvanted vaccine dose, broadly
cross- reactive antibodies produced by the immune system were mostly
directed against the stem. This first wave came mostly from pre-existing
memory B cells. After the second dose, the antibodies were more directed against the head, coming from strain-specific nai"ve B cells.



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The researchers also offered an explanation for the shift in the antibody response after the second dose: essentially, the immune system is getting
in its own way. After the second vaccination, the antibodies against
the stem region are still in the body and they appear to be covering
up those parts of the viral hemagglutinin protein, a phenomenon called
"epitope blocking." "This is something that many flu vaccine studies
have observed, but now we have a possible mechanistic explanation and
good evidence for it," Ahmed says.

Collaborators from Stanford University and Icahn School of Medicine at
Mount Sinai contributed to the paper.

The research at Emory was supported by the National Institute of Allergy
and Infectious Diseases (U19AI109946, R21AI139813, U01A1141990, AI117891)
and the Centers of Excellence in Influenza Research and Surveillance,
via Health and Human Services contracts (HHSN2722019, HHSN272201400004C
and HHSN272201400008C).


========================================================================== Story Source: Materials provided by Emory_Health_Sciences. Note: Content
may be edited for style and length.


========================================================================== Journal Reference:
1. Ali H. Ellebedy, Raffael Nachbagauer, Katherine J. L. Jackson,
Ya-Nan
Dai, Julianna Han, Wafaa B. Alsoussi, Carl W. Davis, Daniel
Stadlbauer, Nadine Rouphael, Veronika Chromikova, Megan McCausland,
Cathy Y. Chang, Mario Cortese, Mary Bower, Chakravarthy Chennareddy,
Aaron J. Schmitz, Veronika I. Zarnitsyna, Lilin Lai, Arvind
Rajabhathor, Cheyann Kazemian, Rustom Antia, Mark J. Mulligan,
Andrew B. Ward, Daved H. Fremont, Scott D. Boyd, Bali Pulendran,
Florian Krammer, Rafi Ahmed. Adjuvanted H5N1 influenza vaccine
enhances both cross-reactive memory B cell and strain- specific
naive B cell responses in humans. Proceedings of the National
Academy of Sciences, 2020; 201906613 DOI: 10.1073/pnas.1906613117 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/07/200716122917.htm

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