SARS-CoV-2: An Alternative Development Strategy for Second Generation Vaccines aimed at Combatting Escape Variants

 

I’m posting an update on progress with our Covid19 vaccines in the hope that it will promote some discussion on where we should go in future. I will also attempt to update this blog and the website on future developments with vaccines and on the course of the pandemic generally.

You can see some more detailed proposals on the website at https://sites.google.com/view/vivweb01/covid19.

SARS-CoV-2 is the virus which causes Covid 19 symptoms. Since Covid19 is a notifiable, and still potentially fatal, disease SARS-Cov-2 variants of concern (VOCs) have been a ‘hot’ pandemic news item since the start of the pandemic, when it was realised that the virus was evolving into different and potentially more dangerous forms.

Identifying and tracking new variants has been one of the principal concerns of governments in the developed world, and continues to be a key element in managing Covid19.

Why are these new variants important ? – you can see a more detailed answer to this question, and some thoughts on viral evolution and the direction we should take to combat it, in my website article. I have also published a detailed review which you can download from the homepage.

Where are we now ? - the identification and rapid spread of the Omicron variant led to a flurry of additional social distancing measures in November 2021. Since then it has emerged that the new variant’s effects appear milder than previous dominant variants. Several new sub-variants of Omicron has already emerged (BA.2, 4 and 5.), displaying a further increase in infectivity but no obvious change in vaccine resistance or the capacity to cause serious illness.

All this has led to a widespread relaxation of prevention measures and a general feeling that ‘it’s (almost) all over’ amongst the UK population....

We may need to re-think this view of the pandemic for a number of reasons:

1) The lower frequency of hospitalisation and deaths is likely to be due largely to our increased levels of immunity, rather than the properties of the virus itself

2)  Immunity declines to a low level within 6 months of a booster vaccination with current vaccines, or following an active infection. We will therefore need to continue boosting our population regularly to avoid increases in hospitalisations, and keep our permanently overburdened NHS from collapsing. It could be difficult to sustain the current effort indefinitely if ‘vaccination fatigue’ sets in..

3)   SARS-CoV-2 is now incredibly infectious, having ‘honed’ its ability to get into our cells to a fine art through multiple mutations over the last 2 years . This means it will be virtually impossible to eradicate, and infection rates are likely to remain stubbornly high.

4)   The virus will continue mutating, and as a result we could at any time be faced with a variant which defeats all our currently approved vaccines, given that these are all directed against the spike protein. Since the devastating effects experienced by some are primarily driven by their own immune reactions to the virus, we should expect a concomitant rise in hospitalisations and deaths if this happens.

5)   An even greater concern is the known ability of SARS-CoV-2 to cross the species barrier quite readily. If it jumps from humans back into an intermediate animal host with which we have close contact, then jumps back again in extensively mutated form, our immune systems may not recognise it, and we could be back to ‘square one’ with largely ineffective vaccines and minimal acquired protection. Coronaviruses have 'form' for this, and the previous two epidemics (SARS-CoV-1 in 2003 and MERS-CoV in 2011) are both known to have had zoonotic origins. Conspiracy theories notwithstanding, SARS-CoV-2 itself is highly likely to have arisen in the same way.

While not wishing to appear alarmist at a time when we have a lot of other things to worry about, I believe we should not lose sight of the risks. We need to address these, and there is a strong case for stepping up the vaccine development campaign, and focusing on 2^nd Generation vaccines with more resistance to viral adaptation.

The website article describes how we could use existing technology to do this. 

An approach such as that recommended in the website article could also help protect against species 'jumps' described in point 5) by taking advantage of viral elements less likely to mutate, and known to be closely related between different species strains.

I intend to update the website page and the full paper regularly in the light of any relevant developments, and will post here when these happen, wherever possible.

(For info., the website itself has not yet been indexed by Google, despite being fully indexed by most other major search engines – see my first post for some comments on the limitations of Google indexing.)

Viv

Update 9.2.22: Two new multi-antigen vaccine candidates involving SARS-CoV-2 structural antigens other than the spike protein are in pre-clinical development and recently report their intention to submit CTA/NDAs for human clinical trials in mid 2022 . The pre-clinical data from both indicate good immune responses from the non-spike antigens, confirming previous observations, and providing an optimistic outlook for success in humans. See the website link above for details and references.

Update 12.6.22: As predicted, the case rate is now starting to rise again in the UK. The latest UK wide estimate is ca 1 in 65 of the population is infected, up from 1 in 75 last week. Scotland seems to be the worst of the home nations affected with a rise from 1:50 last week to 1:40 this week. Two new Omicron sub-variants (BA.4 and BA.5) were identified in South Africa (yet again) and confirmed as having greater infectivity than earlier sub-variants. It is these that appear to be driving the uptick in case numbers in Europe and UK. It may also be relevant that in the UK, only the over 75s were offered an additional booster injection this Spring. The rest of us will be well over 6 months post-last boost at this point, and we know that immunity falls away to 'memory' baseline levels by 6 months. There is also some evidence from SA studies that both new variants may be better able to evade our vaccines (cf the Beta variant, also originating in SA, which rendered the AZ vaccine effectively useless there in 2021). Neither new sub-variant appears to produce more severe disease.

Update 3.9.22: Recent work has shown that S2-directed vaccines generate good neutralising antibody responses and have the potential to be more resistant to new S-protein variants than conventional whole –S protein vaccines The S2 region also carries significant sequence homology with other coronavirus strains, and may provide additional protection against one or more of the ‘common-cold’ coronaviruses. A promising viral antigen 'combi' m-RNA vacccine might therefore be RBD-S + S2-S + Nucleocapsid.

Version Date: 3.9.22