Vaccine efficacy and immune interference: co-administration of COVID-19 and influenza vaccines

As we move towards the second anniversary of the COVID-19 pandemic, attention widens to encompass the range of unintended health care consequences of these unprecedented times and measures. Against this background, efforts have been made to analyze the data and predict what the winter months will look like in terms of the interaction between SARS-CoV-2 infections and other common respiratory viruses, influenza and respiratory syncytial virus. To some extent, there is still no consensus within the scientific and medical communities about the risk and impact of concomitant respiratory infections: on the one hand, containment and other mitigating measures that have limited the spread of COVID-19 should have limited influenza and respiratory syncytial virus as well.
1
Seasonally delayed increase in RSV observed during the COVID-19 pandemic.

,

2
  • Groves HE
  • Piché-Renaud PP
  • Peci A
  • et al.
The Impact of the COVID-19 Pandemic on Influenza, Respiratory Syncytial Virus, and the Circulation of Other Seasonal Respiratory Viruses in Canada: A Population-Based Study.

On the other hand, children in particular might have an increased vulnerability, having now missed almost 2 years of normal interactions that initiate immunity, and adults will have seen their immunity waned.

3
Winter pressure: RSV, flu and COVID-19 could push NHS to breaking point, report warns.

,

4
The Academy of Medical Sciences
COVID-19: preparing for the future. Looking ahead to winter 2021/22 and beyond.

Admittedly, there is little data on which to base precise predictions on the influenza strains most likely to circulate this winter. We must also consider the fairly unexplored territory of the interactive effects of respiratory pathogens: not much is known about the consequences of co-infection with these pathogens, but since each is associated with a somewhat nuanced inflammatory pulmonary pathology, serious additive effects could be anticipated. . At a time when many countries have national COVID-19 vaccination programs, this uncertainty has raised the logistical question of the nature of co-administration programs for the influenza vaccine and the SARS-CoV-2 vaccine. In some ways, there has been no better time to roll out such respiratory vaccination programs. Public confidence in vaccines is high, having largely overcome a considerable degree of reluctance in many countries, and national logistics for delivering immunization programs have been impressive.

NVX-CoV2373 vaccine (i.e. Novavax) is an adjuvanted recombinant protein vaccine, which has performed fairly well in terms of safety, immunogenicity and efficacy in clinical trials.
5
  • Heath PT
  • Galiza EP
  • Baxter DN
  • et al.
Safety and efficacy of the NVX-CoV2373 COVID-19 vaccine.

So what if you co-administer a seasonal flu vaccine in one arm and a COVID-19 vaccine in the other arm? To answer this question by Lancet respiratory medicine, Seth Toback and his colleagues conducted a sub-study

6
  • Toback S
  • Galiza E
  • Cosgrove C
  • et al.
Safety, immunogenicity and efficacy of a COVID-19 vaccine (NVX-CoV2373) co-administered with seasonal influenza vaccines: an exploratory sub-study of a randomized phase 3 trial, without the knowledge of an observer and placebo controlled.

randomized, blinded, placebo-controlled phase 3 trial that evaluated the safety and efficacy of NVX-CoV2373.

5
  • Heath PT
  • Galiza EP
  • Baxter DN
  • et al.
Safety and efficacy of the NVX-CoV2373 COVID-19 vaccine.

In the substudy, Toback and colleagues reported the results of the influenza co-administration cohort, which recruited 431 people to receive the seasonal influenza vaccine (as well as NVX-CoV2373 or a placebo). The study examined reactogenicity, immunogenicity and efficacy. Interestingly, their results included a slight increase in reactogenicity in the double vaccination group (i.e., and a modest decrease in anti-SARS-CoV-2 anti-peak protein IgG antibodies, but with no overall difference in efficacy. NVX-CoV2373 vaccine So the answer is that the co-administration of the two vaccines is safe and effective.

Why should this find be a surprise? So far, the advice has often been that there should be an interval of at least 1 week between vaccinations. As new vaccines rolled out at such a rapid pace while trying to keep the bar high for safety, a high degree of caution was warranted in the uncharted territory of vaccine co-administration. However, an unforeseen benefit of the imperative of so-called rapid progress has been that decisions have at times had to challenge long-held but poorly substantiated assumptions. Part of the caution about co-administering vaccines stems from a fairly old theme within vaccinology and immunology, namely so-called vaccine interference. This term has been taken to mean slightly different things in different contexts. In its simplest form, this was a hypothetical case picked up by people skeptical of combination vaccines for children such as the diphtheria, tetanus and pertussis vaccine or the measles vaccine, mumps and rubella.
7
  • Stowe J
  • Andres N
  • Taylor B
  • et al.
No evidence of increased bacterial and viral infections after measles, mumps and rubella vaccine.

At the heart of the matter was a hypothesis that the immune system could be overloaded by this simultaneous exposure and that this effect would lead to a weakened response to heterologous infections. Over time, more and more evidence against this idea has been reported.

8
A guide to vaccinology: from basic principles to new developments.

The concept has always been confusing to grassroots immunologists, accustomed to thinking that a person’s immune repertoire has the capacity to generate several billion different B cell receptor sequences (each trigger the production of specific antibodies). These receptors must have the ability to evolve during natural exposure to recognize the thousands of microbial epitopes presented to them at any given time by an encounter with large complex proteomes, for example, from Epstein Barr virus or Mycobacterium tuberculosisor even several pathogens at the same time. Against this background, it is perhaps easy to understand why immunologists were not wowed by the suggestion that switching from one to two or two to three simultaneous vaccine components would somehow other the whole immune system in disarray. However, a version of the immune interference argument still exists that has stood the test of time, but is much less macroscopic in scope: this notion argues that natural microbial variants – for example, a parasite or a virus – can act as competitors. antagonists (i.e. modified peptide ligands), reprogramming the protective immune response.

9
  • Plebanski M
  • Lee EAM
  • Hannan CM
  • et al.
The modified peptide ligands narrow the repertoire of cellular immune responses by interfering with the priming of T cells.

,

ten
  • Chief Justice Reynolds
  • Pade C
  • Gibbons JM
  • et al.
Previous infection with SARS-CoV-2 rescues B and T cell responses to variants after the first dose of vaccine.

In summary, COVID-19 vaccine development programs and successes have energized the whole of vaccinology, giving the confidence to test new protocols and protect against various pathogens, even if that means administering the different vaccines at the same time. time.

DMA and RJB report the remuneration of consultants to Oxford ImmunoTec.

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    Lancet Respir Med. 2021; ()

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    Vaccine. 2009; 27: 1422-1425

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    The modified peptide ligands narrow the repertoire of cellular immune responses by interfering with the priming of T cells.

    Nat Med. 1999; 5: 565-571

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    Previous infection with SARS-CoV-2 rescues B and T cell responses to variants after the first dose of vaccine.

    Science. 2021; ()

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Hector Hedgepeth

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