Can Limiting the Initiation Dose of a SARS-CoV-2 Vaccine Improve Immunity?

Several vaccines have been developed, approved and deployed to prevent coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 infection (SARS-CoV-2). However, there is growing concern that a sufficient number of vaccine doses may not be available to rapidly promote global herd immunity. This situation has led researchers to explore the possibility of administering partial doses of the vaccine to increase coverage.

But that, in turn, raises the question of how the fractionation of the vaccine affects the immunity elicited by the vaccine. In a vaccine split (also known as a spared dose), a smaller amount of antigen would be used per dose to increase the number of people who can be vaccinated with a given amount of vaccine.

In a recently published article on the bioRxiv * server, researchers at Northwestern University and the University of Rochester in the United States addressed this question in their study. The researchers also examined whether vaccines administered around the world could confer sterilizing immunity while preventing serious illness and death.

A rationale for splitting SARS-CoV-2 vaccines is that it may result in broader herd immunity even if the vaccine is only partially effective and this could have a more striking effect by blocking transmission to the body. population level. “

Using an adenovirus-based vaccine encoding the SARS-CoV-2 spike protein (Ad5-SARS-2 spike), researchers investigated how the priming dose of a vaccine against SARS-CoV-2 affects long-term immunity in mice against SARS-CoV-2. This vaccine is similar to that used in the CanSino and Sputnik V vaccines.

They found that the low dose (LD) initial dose induced weaker immune responses compared to the standard initial dose (SD). However, researchers reported that LD prime elicited qualitatively superior immune responses. And upon stimulation, the LD-primed mice exhibited much more potent immune responses.

In particular, researchers have found that limiting the initiation dose of a SARS-CoV-2 vaccine can confer an unexpected qualitative benefit to T cell and antibody responses. They showed that an LD prime promotes Tcm differentiation, characterized by a strong expression of CD127, the alpha chain of the IL-7 receptor, which allows the T cell to survive in the long term.

In addition, the researchers observed that the LD / SD pattern induced superior antibody responses compared to the SD / SD pattern. Thus, a “soft” primer antigen also generates memory B cell responses with significantly greater anamnestic capacity.

Because the effect of an LD prime is surprisingly more on antibody responses than on T cell responses, the researchers added that their future studies will aim to understand how LD prime affects B cell differentiation.

Based on the data from this study, the researchers say that limiting the priming dose of a SARS-CoV-2 vaccine can confer unexpected benefits. A single shot of LD / SD provided sterilizing protection. The protective benefit may also be long term, where in most cases vaccine-induced responses may decrease.

The researchers also pointed out that the LD / SD regimen may also be useful in improving vaccine effectiveness in people who develop suboptimal immune responses to vaccines and who may benefit from a higher level of immune responses. With the looming threat of SARS-CoV-2 variants and the re-emergence of SARS-CoV-1, researchers have also shown that the LD / SD pattern results in improved cross-reactive antibody responses compared to SD / SD. .

While researchers have shown that fractionating the priming dose of an adenovirus-based SARS-CoV-2 vaccine confers an unexpected immunological benefit, the minimum level of immune responses required to protect against COVID -19 severe is not yet clear.

They also noted that low levels of immune responses protect individuals from COVID-19, explaining the extraordinary success of several experimental SARS-CoV-2 vaccines over the past year.

Vaccine splitting is an effective strategy to expand vaccine supply and thwart the pandemic causing infection. Based on the results of this study, optimization of current vaccine regimens may warrant reassessment. These results may be useful for improving vaccine availability and for rational vaccine design, the researchers conclude.

*Important Notice

bioRxiv publishes preliminary scientific reports which are not peer reviewed and, therefore, should not be considered conclusive, guide clinical practice / health-related behaviors, or treated as established information.